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1
Alloway, K. D., M. J. Johnson, and M. B. Wallace. "Thalamocortical interactions in the somatosensory system: interpretations of latency and cross-correlation analyses." Journal of Neurophysiology 70, no. 3 (September 1, 1993): 892–908. http://dx.doi.org/10.1152/jn.1993.70.3.892.
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1. Isolated extracellular neuronal responses to cutaneous stimulation were simultaneously recorded from corresponding peripheral representations in the ventrobasal nucleus and primary somatosensory cortex of intact, halothane-anesthetized rats. Thalamic and cortical neurons representing hairy skin on the forelimb were activated by hair movements produced by a series of 50 or 100 discrete air jets. A corresponding set of neurons representing the glabrous pads of the hind paw were activated by a similar number of punctate mechanical displacements. 2. Cortical electrode penetrations were histologically reconstructed, and 118 neurons in the glabrous skin representation exhibited cutaneous responses that were categorized into supragranular, granular, or infragranular groups according to their laminar position. Minimum latencies of cortical neurons responding to glabrous skin displacement were analyzed, and significant differences were found in the distribution of minimum latencies for the different cortical layers. Mean values for minimum latencies in the infragranular and granular layers were 15.8 and 16.3 ms, respectively, whereas supragranular neurons were characterized by minimum latencies having a mean of 20 ms. The differences between these groups suggests that stimulus-induced afferent activity reaches infragranular and granular layers before contacting supragranular neurons. Average latencies were also calculated on responses occurring during the 1st 20 trials, but the cortical distributions of these values overlapped considerably, and differences between the laminar groups were not statistically significant. 3. In several recording sites, two cortical neurons were recorded simultaneously, and the response latencies of these matched pairs were often substantially different despite the similarity in laminar position. This result indicates that laminar location is not the only determinant of response latency and that serially organized circuits are distributed within, as well as between, cortical layers. 4. From a sample of 302 neurons exhibiting cutaneous responses within histologically identified regions of thalamus or cortex, a set of 143 pairs of neurons recorded simultaneously from both regions was available for cross-correlation analysis. Significant thalamocortical interactions were found in 38 neurons pairs. Analysis of these significant interactions revealed that thalamocortical connection strength, as measured by neuronal efficacy, was two to four times larger for neuron pairs having the cortical cell in granular layer IV than for neuron pairs having an extragranular layer cortical neuron. There was no difference in thalamocortical connection strength between neuron pairs containing supra- or infragranular cortical neurons. 5. Summed peristimulus time histograms revealed stimulus-locked inhibition of spontaneous activity in 4% (8/195) or cortical and 18% (20/107) of thalamic neurons.(ABSTRACT TRUNCATED AT 400 WORDS)
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Collins, Christine E., Emily C. Turner, Eva Kille Sawyer, Jamie L. Reed, Nicole A. Young, David K. Flaherty, and Jon H. Kaas. "Cortical cell and neuron density estimates in one chimpanzee hemisphere." Proceedings of the National Academy of Sciences 113, no. 3 (January 4, 2016): 740–45. http://dx.doi.org/10.1073/pnas.1524208113.
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The density of cells and neurons in the neocortex of many mammals varies across cortical areas and regions. This variability is, perhaps, most pronounced in primates. Nonuniformity in the composition of cortex suggests regions of the cortex have different specializations. Specifically, regions with densely packed neurons contain smaller neurons that are activated by relatively few inputs, thereby preserving information, whereas regions that are less densely packed have larger neurons that have more integrative functions. Here we present the numbers of cells and neurons for 742 discrete locations across the neocortex in a chimpanzee. Using isotropic fractionation and flow fractionation methods for cell and neuron counts, we estimate that neocortex of one hemisphere contains 9.5 billion cells and 3.7 billion neurons. Primary visual cortex occupies 35 cm2 of surface, 10% of the total, and contains 737 million densely packed neurons, 20% of the total neurons contained within the hemisphere. Other areas of high neuron packing include secondary visual areas, somatosensory cortex, and prefrontal granular cortex. Areas of low levels of neuron packing density include motor and premotor cortex. These values reflect those obtained from more limited samples of cortex in humans and other primates.
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Sajjad, Hassan, Nadir Durrani, and Fahim Dalvi. "Neuron-level Interpretation of Deep NLP Models: A Survey." Transactions of the Association for Computational Linguistics 10 (2022): 1285–303. http://dx.doi.org/10.1162/tacl_a_00519.
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Abstract The proliferation of Deep Neural Networks in various domains has seen an increased need for interpretability of these models. Preliminary work done along this line, and papers that surveyed such, are focused on high-level representation analysis. However, a recent branch of work has concentrated on interpretability at a more granular level of analyzing neurons within these models. In this paper, we survey the work done on neuron analysis including: i) methods to discover and understand neurons in a network; ii) evaluation methods; iii) major findings including cross architectural comparisons that neuron analysis has unraveled; iv) applications of neuron probing such as: controlling the model, domain adaptation, and so forth; and v) a discussion on open issues and future research directions.
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Zhang, Mengliang, and Kevin D. Alloway. "Stimulus-Induced Intercolumnar Synchronization of Neuronal Activity in Rat Barrel Cortex: A Laminar Analysis." Journal of Neurophysiology 92, no. 3 (September 2004): 1464–78. http://dx.doi.org/10.1152/jn.01272.2003.
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We used cross-correlation analysis to characterize the coordination of stimulus-induced neuronal activity in the primary somatosensory barrel cortex of isoflurane-anesthetized rats. On each trial, multiple whiskers were simultaneously deflected at frequencies that corresponded to 2, 5, 8, or 11 Hz. Among 476 neuron pairs that we examined, 342 (71.8%) displayed significant peaks of synchronized activity that exceeded the 99.9% confidence limits. The incidence and strength of these functional associations varied across different cortical layers. Only 52.9% of neuron pairs in layer IV displayed synchronized responses, whereas 84.1% of the infragranular neuron pairs were synchronized during whisker stimulation. Neuronal synchronization was strongest in the infragranular layers, weakest in layer IV, and varied according to the columnar configuration of the neuron pairs. Thus correlation coefficients were largest for neuron pairs in the same whisker barrel row but were smallest for neurons in different rows and arcs. Spontaneous activity in the infragranular layers was also synchronized to a greater degree than in the other layers. Although infragranular neuron pairs displayed similar amounts of synchronization in response to each stimulus frequency, granular and supragranular neurons were synchronized mainly during stimulation at 2 or 5 Hz. These results are consistent with previous studies indicating that infragranular neurons have intrinsic properties that facilitate synchronized activity, and they suggest that neuronal synchronization plays an important role in transmitting sensory information to other cortical or subcortical brain regions.
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Howarth, Clare, Claire M. Peppiatt-Wildman, and David Attwell. "The Energy Use Associated with Neural Computation in the Cerebellum." Journal of Cerebral Blood Flow & Metabolism 30, no. 2 (November 4, 2009): 403–14. http://dx.doi.org/10.1038/jcbfm.2009.231.
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The brain's energy supply determines its information processing power, and generates functional imaging signals, which are often assumed to reflect principal neuron spiking. Using measured cellular properties, we analysed how energy expenditure relates to neural computation in the cerebellar cortex. Most energy is used on information processing by non-principal neurons: Purkinje cells use only 18% of the signalling energy. Excitatory neurons use 73% and inhibitory neurons 27% of the energy. Despite markedly different computational architectures, the granular and molecular layers consume approximately the same energy. The blood vessel area supplying glucose and O2 is spatially matched to energy consumption. The energy cost of storing motor information in the cerebellum was also estimated.
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Li, Chenyang, Tongchuang Lu, Chengfang Pan, and Changlong Hu. "Glucocorticoids Selectively Inhibit Hippocampal CA1 Pyramidal Neurons Activity Through HCN Channels." International Journal of Molecular Sciences 25, no. 22 (November 7, 2024): 11971. http://dx.doi.org/10.3390/ijms252211971.
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Glucocorticoids are known to influence hippocampal function, but their rapid non-genomic effects on specific neurons in the hippocampal trisynaptic circuit remain underexplored. This study investigated the immediate effects of glucocorticoids on CA1 and CA3 pyramidal neurons, and dentate gyrus (DG) granule neurons in rats using the patch-clamp technique. We found that a 5 min extracellular application of corticosterone significantly reduced action potential firing frequency in CA1 pyramidal neurons, while no effects were observed in CA3 or DG neurons. The corticosterone-induced inhibition in CA1 was blocked by the glucocorticoid receptor antagonist CORT125281, but remained unaffected by the mineralocorticoid receptor antagonist spironolactone. Notably, membrane-impermeable bovine serum albumin-conjugated dexamethasone mimicked corticosterone’s effects on CA1 neurons, which exhibited prominent hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents. Pyramidal neurons in CA3 and granular neurons in the DG showed little HCN channel currents. Corticosterone enhanced HCN channel activity in CA1 neurons via glucocorticoid receptors, and the HCN channel inhibitor ZD7288 abolished corticosterone’s suppressive effects on action potentials. These findings suggest that glucocorticoids selectively inhibit CA1 pyramidal neuron activity through HCN channels, providing new insight into the mechanisms of glucocorticoid action in hippocampal circuits.
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Jolly, R. D., A. C. Johnstone, E. J. Norman, J. J. Hopwood, and S. U. Walkley. "Pathology of Mucopolysaccharidosis IIIA in Huntaway Dogs." Veterinary Pathology 44, no. 5 (September 2007): 569–78. http://dx.doi.org/10.1354/vp.44-5-569.
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Dogs with mucopolysaccharidosis (MPS) IIIA were bred within an experimental colony. As part of characterizing them as a model for testing therapeutic strategies for the analogous disease of children, a pathologic study was undertaken. By histology, there were variably stained storage cytosomes within neurons, including many that stained for gangliosides. On ultrastructure examination, these cytosomes contained either moderately dense granular material, tentatively interpreted as precipitated glycosaminoglycan; a variety of multilaminar bodies, interpreted as being associated with secondary accumulation of gangliosides; or a mixture of both types. In the liver, storage vesicles also contained excess glycogen as a secondary storage product. In various tissues, there were large foamy macrophages. In the brain, many of these were in juxtaposition with neurons, and, on ultrastructure examination, they contained storage cytosomes similar to those in neurons. However, the neuron in association with such a macrophage frequently showed little such material.
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Medini, Chaitanya, Bipin Nair, Egidio D'Angelo, Giovanni Naldi, and Shyam Diwakar. "Modeling Spike-Train Processing in the Cerebellum Granular Layer and Changes in Plasticity Reveal Single Neuron Effects in Neural Ensembles." Computational Intelligence and Neuroscience 2012 (2012): 1–17. http://dx.doi.org/10.1155/2012/359529.
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The cerebellum input stage has been known to perform combinatorial operations on input signals. In this paper, two types of mathematical models were used to reproduce the role of feed-forward inhibition and computation in the granular layer microcircuitry to investigate spike train processing. A simple spiking model and a biophysically-detailed model of the network were used to study signal recoding in the granular layer and to test observations like center-surround organization and time-window hypothesis in addition to effects of induced plasticity. Simulations suggest that simple neuron models may be used to abstract timing phenomenon in large networks, however detailed models were needed to reconstruct population coding via evoked local field potentials (LFP) and for simulating changes in synaptic plasticity. Our results also indicated that spatio-temporal code of the granular network is mainly controlled by the feed-forward inhibition from the Golgi cell synapses. Spike amplitude and total number of spikes were modulated by LTP and LTD. Reconstructing granular layer evoked-LFP suggests that granular layer propagates the nonlinearities of individual neurons. Simulations indicate that granular layer network operates a robust population code for a wide range of intervals, controlled by the Golgi cell inhibition and is regulated by the post-synaptic excitability.
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Kreiner, T., W. Sossin, and R. H. Scheller. "Localization of Aplysia neurosecretory peptides to multiple populations of dense core vesicles." Journal of Cell Biology 102, no. 3 (March 1, 1986): 769–82. http://dx.doi.org/10.1083/jcb.102.3.769.
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Many neurons in the mollusc Aplysia are identifiable and provide a useful model system for investigating the cellular mechanisms used by the neuroendocrine system to mediate simple behaviors. In this study we determined the subcellular localization of eight Aplysia neuropeptides using immunogold labeling techniques, and analyzed the size distribution of dense core and granular vesicles in peptidergic neurons. Recent observations demonstrate that many neurons use multiple chemical messengers. Thus, an understanding of the functional significance of cotransmitters requires an analysis of their relative subcellular distributions. The peptides are expressed in a subset of neurons, or the exocrine atrial gland, and are primarily localized to dense core vesicles. Multiple regions of precursors which are cleaved into several components are co-localized. Each neuron has a distinct size distribution of peptide-containing dense core vesicles ranging in size from 65 to 600 nm. The atrial gland contains very large (up to 2 micron) peptide-containing granules. Single neurons have multiple populations of granules whose quantal sizes agree with predictions based on physical constraints. Some cells contain very large peptide-containing granules which are found in the cell soma and not in processes. Thus, the genetic determination of neuronal cell type includes not only transmitter choices but also multiple modes of packaging the intercellular messengers.
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Alp, Murat, and Francis A. Cucinotta. "Biophysics Model of Heavy-Ion Degradation of Neuron Morphology in Mouse Hippocampal Granular Cell Layer Neurons." Radiation Research 189, no. 3 (March 2018): 312–25. http://dx.doi.org/10.1667/rr14923.1.
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Schofield, Geoffrey G., Henry L. Puhl, and Stephen R. Ikeda. "Properties of Wild-Type and Fluorescent Protein-Tagged Mouse Tetrodotoxin-Resistant Sodium Channel (NaV1.8) Heterologously Expressed in Rat Sympathetic Neurons." Journal of Neurophysiology 99, no. 4 (April 2008): 1917–27. http://dx.doi.org/10.1152/jn.01170.2007.
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The tetrodotoxin (TTX)-resistant Na+ current arising from NaV1.8-containing channels participates in nociceptive pathways but is difficult to functionally express in traditional heterologous systems. Here, we show that injection of cDNA encoding mouse NaV1.8 into the nuclei of rat superior cervical ganglion (SCG) neurons results in TTX-resistant Na+ currents with amplitudes equal to or exceeding the currents arising from natively expressing channels of mouse dorsal root ganglion (DRG) neurons. The activation and inactivation properties of the heterologously expressed NaV1.8 Na+ channels were similar but not identical to native TTX-resistant channels. Most notably, the half-activation potential of the heterologously expressed NaV1.8 channels was shifted about 10 mV toward more depolarized potentials. Fusion of fluorescent proteins to the N- or C-termini of NaV1.8 did not substantially affect functional expression in SCG neurons. Unexpectedly, fluorescence was not concentrated at the plasma membrane but found throughout the interior of the neuron in a granular pattern. A similar expression pattern was observed in nodose ganglion neurons expressing the tagged channels. In contrast, expression of tagged NaV1.8 in HeLa cells revealed a fluorescence pattern consistent with sequestration in the endoplasmic reticulum, thus providing a basis for poor functional expression in clonal cell lines. Our results establish SCG neurons as a favorable surrogate for the expression and study of molecularly defined NaV1.8-containing channels. The data also indicate that unidentified factors may be required for the efficient functional expression of NaV1.8 with a biophysical phenotype identical to that found in sensory neurons.
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Wang, Rui-Yu, Gregory N. Fuller, Teresa McQueen, Yue-Xi Shi, Richard E. Champlin, and Michael Andreeff. "Distribution and Differentiation of Donor-Derived Bone Marrow Stem Cells in Various Areas of the Human Brain." Blood 106, no. 11 (November 16, 2005): 1685. http://dx.doi.org/10.1182/blood.v106.11.1685.1685.
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Abstract Hematopoietic stem cells (HSCs) resident in the bone marrow or in circulation, have shown the capacity of transdifferentiation into mature neuronal lineages in the brain (Joanna E et al, Stem Cells 2004, 22:487–500 and Cogle et al, The Lancet, 2004, 363:1432–1437). To determine whether this phenomenon occurs at different frequencies in different regions of the brain, immunohistochemical staining with anti-neuron antibody (brown nuclear localization) and anti-CD45 antibody (leukocyte marker, red cytoplasm localization) combined with fluorescence in situ hybridization (FISH) (chromosome X and Y), were performed on autopsy samples from different regions of the brain of two leukemia patients who had undergone sex-mismatched bone marrow transplantation to identify donor-derived neuron and donor leukocytes. The regions of human brain analyzed included midbrain, cerebellum, hippocampus, olfactory bulbs, medulla, pons, and parietal cortex. The distribution of donor-derived leukocytes and donor-derived transdifferentiated neuron in various regions of the bone marrow transplanted recipient’s brain was analyzed in two cases. Approximately 16,500–45,720 cells (average 32,300 cells) on each tissue section were analyzed. For the deep hypercellular granular layer and molecular layer of cerebellum about 343,000 cells were analyzed. An increased percentage of donor leukocytes was found in the hippocampus in both cases (0.8% in case 1 and 1.4% in case 2). In case 1, an increased percentage of donor leukocytes were also found in the pons (0.9%) and olfactory bulbs (1.2%). Transdifferentiation of donor-derived bone marrow stem cells was determined by enumeration of donor-derived mature neuronal cells as percentage in total chromosome XY - positive cells in each region of the brain. The frequency of donor-derived neurons was between 0.6% to 1.7% in cerebellum (0.6% in case 1 and 0.7% in case 2), medulla (1.6% in case 1 and 1.0% in case 2), hippocampus (0.7% in case 1 and 0.6% in case 2), and olfactory bulbs (0.8% in case 1). We did not find donor-derived transdifferentiated neuronal cells in the medulla, pons and parietal cortex in both cases. To determine whether CD34+ cells or mesenchymal stem cells (MSC) have higher potential to differentiation into mature neurons, CD34+ cells and MSC were cultured in transwells with mouse brain extract, respectively. The expression level of neuron specific gene was analyzed after 4 days using western blotting. The levels in CD34+ cells were 1.14-fold higher than in MSC. No neuron specific gene expression was found in CD34+ cells and MSC. These results suggested that 1) the different frequencies of donor leukocytes in regions indicate that the engraftment of circulated donor cells is different in different regions of the brain. 2) Donor-derived mature neurons were found in regions of the midbrain, cerebellum, hippocampus and olfactory bulbs. No donor-derived neurons were found in medulla, pons, and parietal cortex in the two cases analyzed. 3) CD34+ cells have higher potential to differentiation into neurons than MSC.
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Straka, Hans, James C. Beck, Angel M. Pastor, and Robert Baker. "Morphology and Physiology of the Cerebellar Vestibulolateral Lobe Pathways Linked to Oculomotor Function in the Goldfish." Journal of Neurophysiology 96, no. 4 (October 2006): 1963–80. http://dx.doi.org/10.1152/jn.00334.2006.
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Intracellular recording and single-cell labeling were combined to investigate the oculomotor circuitry of the goldfish cerebellar vestibulolateral lobe, consisting of the eminentia granularis (Egr) and caudal lobe. Purkinje cells exhibiting highly conserved vertebrate electrophysiological and morphological properties provide the direct output from the caudal lobe to the vestibular nuclei. Biocytin labeling of the Egr distinguished numerous hindbrain precerebellar sources that could be divided into either putative mechano- or vestibulosensitive nuclei based on cellular location and axon trajectories. Precerebellar neurons in a hindbrain nucleus, called Area II, were electrophysiologically characterized after antidromic activation from the Egr (>50% bilateral) and their morphology analyzed after intracellular biocytin labeling ( n = 28). Bipolar spindle-shaped somas ranged widely in size with comparably scaled dendritic arbors exhibiting largely closed field configuration. Area II neurons (85%) projected to the ipsilateral Egr with most (93%) sending a collateral through the cerebellar commissure to the contralateral Egr; however, 15% projected to the contralateral Egr by crossing in the ventral hindbrain. Axon terminals in the vestibular nucleus were the only collaterals within the hindbrain. Every Area II neuron received a disynaptic EPSP after contralateral horizontal canal nerve stimulation and a disynaptic IPSP, preceded by a small EPSP (>50%), after ipsilateral activation. Vestibular synaptic potentials were of varying shape/amplitude, unrelated to neuron location in the nucleus, and thus likely a correlate of somadendritic size. The exceptional separation of eye position and eye velocity signals into two separate hindbrain nuclei represents an ideal model for understanding the precerebellar projection to the vestibulocerebellum.
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Komitova, Mila, Ekaterina Perfilieva, Bengt Mattsson, Peter S. Eriksson, and Barbro B. Johansson. "Effects of Cortical Ischemia and Postischemic Environmental Enrichment on Hippocampal Cell Genesis and Differentiation in the Adult Rat." Journal of Cerebral Blood Flow & Metabolism 22, no. 7 (July 2002): 852–60. http://dx.doi.org/10.1097/00004647-200207000-00010.
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The study aimed to elucidate the effects of cortical ischemia and postischemic environmental enrichment on hippocampal cell genesis. A cortical infarct was induced by a permanent ligation of the middle cerebral artery distal to the striatal branches in 6-month-old spontaneously hypertensive rats. Bromodeoxyuridine (BrdU) was administered as 7 consecutive daily injections starting 24 hours after surgery and animals were housed in standard or enriched environment. Four weeks after completed BrdU administration, BrdU incorporation and its co-localization with the neuronal markers NeuN and calbindin D28k, and the astrocytic marker glial fibrillary acidic protein in the granular cell layer and subgranular zone of the hippocampal dentate gyrus were determined with immunohistochemistry and were quantified stereologically. Compared with sham-operated rats, rats with cortical infarcts had a five-to sixfold ipsilateral increase in BrdU-labeled cells. About 80% of the new cells were neurons. Differential postischemic housing did not influence significantly the total number of surviving BrdU-labeled cells or newborn neurons. However, postischemic environmental enrichment increased the ipsilateral generation of astrocytes normalizing the astrocyte-to-neuron ratio, which was significantly reduced in rats housed in standard environment postischemically.
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Schmitt, Andrea, Laura Tatsch, Alisa Vollhardt, Thomas Schneider-Axmann, Florian J. Raabe, Lukas Roell, Helmut Heinsen, Patrick R. Hof, Peter Falkai, and Christoph Schmitz. "Decreased Oligodendrocyte Number in Hippocampal Subfield CA4 in Schizophrenia: A Replication Study." Cells 11, no. 20 (October 15, 2022): 3242. http://dx.doi.org/10.3390/cells11203242.
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Hippocampus-related cognitive deficits in working and verbal memory are frequent in schizophrenia, and hippocampal volume loss, particularly in the cornu ammonis (CA) subregions, was shown by magnetic resonance imaging studies. However, the underlying cellular alterations remain elusive. By using unbiased design-based stereology, we reported a reduction in oligodendrocyte number in CA4 in schizophrenia and of granular neurons in the dentate gyrus (DG). Here, we aimed to replicate these findings in an independent sample. We used a stereological approach to investigate the numbers and densities of neurons, oligodendrocytes, and astrocytes in CA4 and of granular neurons in the DG of left and right hemispheres in 11 brains from men with schizophrenia and 11 brains from age- and sex-matched healthy controls. In schizophrenia, a decreased number and density of oligodendrocytes was detected in the left and right CA4, whereas mean volumes of CA4 and the DG and the numbers and density of neurons, astrocytes, and granular neurons were not different in patients and controls, even after adjustment of variables because of positive correlations with postmortem interval and age. Our results replicate the previously described decrease in oligodendrocytes bilaterally in CA4 in schizophrenia and point to a deficit in oligodendrocyte maturation or a loss of mature oligodendrocytes. These changes result in impaired myelination and neuronal decoupling, both of which are linked to altered functional connectivity and subsequent cognitive dysfunction in schizophrenia.
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Dykes, R. W., and Y. Lamour. "An electrophysiological study of single somatosensory neurons in rat granular cortex serving the limbs: a laminar analysis." Journal of Neurophysiology 60, no. 2 (August 1, 1988): 703–24. http://dx.doi.org/10.1152/jn.1988.60.2.703.
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1. Recordings were made from 545 neurons in somatosensory granular cortex of anesthetized Sprague-Dawley rats. Of this sample, 32% were active spontaneously. Active neurons were not distributed uniformly throughout cortex but were most common in layer V. The highest mean spontaneous discharge frequency also was found in this layer. Cells with the lowest rates of spontaneous activity were located immediately above and below. One subset of spontaneously active neurons was characterized by an unusually high discharge frequency modulated by somatic stimulation. 2. Only 25.8% of the 534 neurons tested in granular cortex could be activated by somatic stimuli. Only 9.4% had cutaneous receptive fields, and 2.4% received deep inputs. The remainder (14.0%) were driven by higher intensity stimuli and could not be classified unequivocally as either cutaneous or deep. The 50 neurons with cutaneous receptive fields were located in the middle third of the cortex, and those with the largest receptive fields were found most superficially. Neurons driven by somatic stimuli were found most frequently in layer Vb, where 44.5% of the sample confirmed histologically to be in layer Vb could be excited. 3. The large proportion of neurons lacking demonstrable somatic inputs was attributed to the use of iontophoretically administered glutamate, which allowed the detection of many unresponsive neurons. This proportion was not reduced by the use of nitrous oxide and halothane as an anesthetic. 4. Neurons activated only by deep inputs were found on the medial and rostral edge of the hindlimb granular cortex, suggesting that deep and cutaneous inputs may be segregated in this species. 5. Electrical stimuli applied to the foot pads activated a sample of neurons differing from those driven by natural somatic stimuli in terms of depth, spontaneous activity, probability of somatic input, and probability of activation by the pyramidal tract. 6. Pyramidal tract neurons tended to be located in layer Vb, were active spontaneously, and had evidence of somatic inputs, although most required relatively intense stimuli to be excited. Other neurons activated synaptically from the pyramidal tract were located in the layers immediately above and below the pyramidal tract neurons. These cells were divided into two groups on the basis of action-potential latency, action-potential shape, and sensitivity to acetylcholine.
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Yousuf, Hanna, Andrew N. Nye, and James R. Moyer. "Heterogeneity of neuronal firing type and morphology in retrosplenial cortex of male F344 rats." Journal of Neurophysiology 123, no. 5 (May 1, 2020): 1849–63. http://dx.doi.org/10.1152/jn.00577.2019.
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This is the first study to demonstrate that granular retrosplenial cortical (gRSC) neurons exhibit five distinctive firing types: regular spiking (RS), regular spiking with an afterdepolarization (RSADP), late spiking (LS), burst spiking (BS), and fast spiking (FS). RSADP neurons were the most frequently observed cell type in adult gRSC neurons. Interestingly, RS neurons without an ADP were most common in gRSC neurons of juvenile rats (PND 14–30). Thus, the ADP property, which was previously shown to enhance neuronal excitability, emerges during development.
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Torti, Emanuele, Giordana Florimbi, Arianna Dorici, Giovanni Danese, and Francesco Leporati. "Towards the Simulation of a Realistic Large-Scale Spiking Network on a Desktop Multi-GPU System." Bioengineering 9, no. 10 (October 11, 2022): 543. http://dx.doi.org/10.3390/bioengineering9100543.
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The reproduction of the brain ’sactivity and its functionality is the main goal of modern neuroscience. To this aim, several models have been proposed to describe the activity of single neurons at different levels of detail. Then, single neurons are linked together to build a network, in order to reproduce complex behaviors. In the literature, different network-building rules and models have been described, targeting realistic distributions and connections of the neurons. In particular, the Granular layEr Simulator (GES) performs the granular layer network reconstruction considering biologically realistic rules to connect the neurons. Moreover, it simulates the network considering the Hodgkin–Huxley model. The work proposed in this paper adopts the network reconstruction model of GES and proposes a simulation module based on Leaky Integrate and Fire (LIF) model. This simulator targets the reproduction of the activity of large scale networks, exploiting the GPU technology to reduce the processing times. Experimental results show that a multi-GPU system reduces the simulation of a network with more than 1.8 million neurons from approximately 54 to 13 h.
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Philbert, M. A., C. M. Beiswanger, T. L. Roscoe, D. K. Waters, and H. E. Lowndes. "Enhanced resolution of histochemical distribution of glucose-6-phosphate dehydrogenase activity in rat neural tissue by use of a semipermeable membrane." Journal of Histochemistry & Cytochemistry 39, no. 7 (July 1991): 937–43. http://dx.doi.org/10.1177/39.7.1865111.
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We examined the histochemical distribution of glucose-6-phosphate dehydrogenase (G6PD) activity in neural tissue using different diffusion barriers. Although polyvinyl alcohol and agar overlays permitted regional localization of G6PD, a semipermeable membrane revealed cellular differences in G6PD activity within populations of neurons. Distribution of G6PD activity in selected regions of the nervous system was examined using the membrane technique. White matter usually exhibited strong G6PD activity. The neuronal somata of the dorsal root ganglia (L4-L6) and anterior horns of the spinal lumbar enlargement demonstrated a variation in activity which was independent of somal size. Satellite cells showed intense activity when the membrane technique was used. Hippocampal pyramidal and granular cells of the dentate gyrus exhibited moderate, uniform G6PD activity, but only weak activity was seen in hippocampal and dentate molecular layers. High levels of activity were observed in the vascular endothelial cells of the brain, spinal cord, and choroid plexus, and in the ependymal cells of the spinal central canal and ventricles of the brain. The superior vestibular nucleus appeared to have little G6PD activity in either the neuron cell bodies or the surrounding parenchyma. The use of a semipermeable membrane for localization of G6PD activity in neural tissues permits enhanced resolution of neuron elements and may provide a more accurate assessment of G6PD activity in histological preparations.
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Macedo-Lima, Matheus, Marco Aurélio M. Freire, Hugo de Carvalho Pimentel, Lívia Cristina Rodrigues Ferreira Lins, Katty Anne Amador de Lucena Medeiros, Giordano Gubert Viola, José Ronaldo dos Santos, and Murilo Marchioro. "Characterization of NADPH Diaphorase- and Doublecortin-Positive Neurons in the Lizard Hippocampal Formation." Brain, Behavior and Evolution 88, no. 3-4 (2016): 222–34. http://dx.doi.org/10.1159/000453105.
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The lizard cortex has remarkable similarities with the mammalian hippocampus. Both regions process memories, have similar cytoarchitectural properties, and are important neurogenic foci in adults. Lizards show striking levels of widespread neurogenesis in adulthood and can regenerate entire cortical areas after injury. Nitric oxide (NO) is an important regulatory factor of mammalian neurogenesis and hippocampal function. However, little is known about its role in nonmammalian neurogenesis. Here, we analyzed the distribution, morphology, and dendritic complexity (Neurolucida reconstructions) of NO-producing neurons through NADPH diaphorase (NADPHd) activity, and how they compare with the distribution of doublecortin-positive (DCX+) neurons in the hippocampal formation of the neotropical lizard Tropidurus hispidus. NADPHd-positive (NADPHd+) neurons in the dorsomedial cortex (DMC; putatively homologous to mammalian CA3) were more numerous and complex than the ones in the medial cortex (MC; putatively homologous to the dentate gyrus). We found that NADPHd+ DMC neurons send long projections into the MC. Interestingly, in the MC, NADPHd+ neurons existed in 2 patterns: small somata with low intensity of staining in the outer layer and large somata with high intensity of staining in the deep layer, a pattern similar to the mammalian cortex. Additionally, NADPHd+ neurons were absent in the granular cell layer of the MC. In contrast, DCX+ neurons were scarce in the DMC but highly numerous in the MC, particularly in the granular cell layer. We hypothesize that NO-producing neurons in the DMC provide important input to proliferating/migrating neurons in the highly neurogenic MC.
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Park, Hae Jeong, Ira Rajbhandari, Han Soo Yang, Soojung Lee, Delia Cucoranu, Deborah S. Cooper, Janet D. Klein, Jeff M. Sands, and Inyeong Choi. "Neuronal expression of sodium/bicarbonate cotransporter NBCn1 (SLC4A7) and its response to chronic metabolic acidosis." American Journal of Physiology-Cell Physiology 298, no. 5 (May 2010): C1018—C1028. http://dx.doi.org/10.1152/ajpcell.00492.2009.
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The sodium-bicarbonate cotransporter NBCn1 (SLC4A7) is an acid-base transporter that normally moves Na+ and HCO3− into the cell. This membrane protein is sensitive to cellular and systemic pH changes. We examined NBCn1 expression and localization in the brain and its response to chronic metabolic acidosis. Two new NBCn1 antibodies were generated by immunizing a rabbit and a guinea pig. The antibodies stained neurons in a variety of rat brain regions, including hippocampal pyramidal neurons, dentate gyrus granular neurons, posterior cortical neurons, and cerebellar Purkinje neurons. Choroid plexus epithelia were also stained. Double immunofluorescence labeling showed that NBCn1 and the postsynaptic density protein PSD-95 were found in the same hippocampal CA3 neurons and partially colocalized in dendrites. PSD-95 was pulled down from rat brain lysates with the GST/NBCn1 fusion protein and was also coimmunoprecipitated with NBCn1. Chronic metabolic acidosis was induced by feeding rats with normal chow or 0.4 M HCl-containing chow for 7 days. Real-time PCR and immunoblot showed upregulation of NBCn1 mRNA and protein in the hippocampus of acidotic rats. NBCn1 immunostaining was enhanced in CA3 neurons, posterior cortical neurons, and cerebellar granular cells. Intraperitoneal administration of N-methyl-d-aspartate caused neuronal death determined by caspase-3 activity, and this effect was more severe in acidotic rats. Administering N-methyl-d-aspartate also inhibited NBCn1 upregulation in acidotic rats. We conclude that NBCn1 in neurons is upregulated by chronic acid loads, and this upregulation is associated with glutamate excitotoxicity.
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Kamiya, Shiori, Tetsuya Kobayashi, and Kazuhiko Sawada. "Tracking of Internal Granular Progenitors Responding to Valproic Acid in the Cerebellar Cortex of Infant Ferrets." Cells 13, no. 4 (February 7, 2024): 308. http://dx.doi.org/10.3390/cells13040308.
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Internal granular progenitors (IGPs) in the developing cerebellar cortex of ferrets differentiate towards neural and glial lineages. The present study tracked IGPs that proliferated in response to valproic acid (VPA) to determine their fate during cerebellar cortical histogenesis. Ferret kits were used to administer VPA (200 μg/g body weight) on postnatal days 6 and 7. EdU and BrdU were injected on postnatal days 5 and 7, respectively, to label the post-proliferative and proliferating cells when exposed to VPA. At postnatal day 20, when the external granule layer was most expanded, EdU- and BrdU-single-labeled cells were significantly denser in the inner granular layer of VPA-exposed ferrets than in controls. No EdU- or BrdU-labeling was found in Purkinje cells and molecular layer interneurons. Significantly higher percentages of NeuN and Pax6 immunostaining in VPA-exposed ferrets revealed VPA-induced differentiation of IGPs towards granular neurons in BrdU-single-labeled cells. In contrast, both EdU- and BrdU-single-labeled cells exhibited significantly greater percentages of PCNA immunostaining, which appeared in immature Bergman glia, in the internal granular layer of VPA-exposed ferrets. These findings suggest that VPA affects the proliferation of IGPs to induce differentiative division towards granular neurons as well as post-proliferative IGPs toward differentiation into Bergmann glia.
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Nixima, Ken'ichi, Kazuo Okanoya, Noritaka Ichinohe, and Tohru Kurotani. "Fast voltage-sensitive dye imaging of excitatory and inhibitory synaptic transmission in the rat granular retrosplenial cortex." Journal of Neurophysiology 118, no. 3 (September 1, 2017): 1784–99. http://dx.doi.org/10.1152/jn.00734.2016.
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Rodent granular retrosplenial cortex (GRS) has dense connections between the anterior thalamic nuclei (ATN) and hippocampal formation. GRS superficial pyramidal neurons exhibit distinctive late spiking (LS) firing property and form patchy clusters with prominent apical dendritic bundles. The aim of this study was to investigate spatiotemporal dynamics of signal transduction in the GRS induced by ATN afferent stimulation by using fast voltage-sensitive dye imaging in rat brain slices. In coronal slices, layer 1a stimulation, which presumably activated thalamic fibers, evoked propagation of excitatory synaptic signals from layers 2–4 to layers 5–6 in a direction perpendicular to the layer axis, followed by transverse signal propagation within each layer. In the presence of ionotropic glutamate receptor antagonists, inhibitory responses were observed in superficial layers, induced by direct activation of inhibitory interneurons in layer 1. In horizontal slices, excitatory signals in deep layers propagated transversely mainly from posterior to anterior via superficial layers. Cortical inhibitory responses upon layer 1a stimulation in horizontal slices were weaker than those in the coronal slices. Observed differences between coronal and horizontal planes suggest anisotropy of the intracortical circuitry. In conclusion, ATN inputs are processed differently in coronal and horizontal planes of the GRS and then conveyed to other cortical areas. In both planes, GRS superficial layers play an important role in signal propagation, which suggests that superficial neuronal cascade is crucial in the integration of multiple information sources. NEW & NOTEWORTHY Superficial neurons in the rat granular retrosplenial cortex (GRS) show distinctive late-spiking (LS) firing property. However, little is known about spatiotemporal dynamics of signal transduction in the GRS. We demonstrated LS neuron network relaying thalamic inputs to deep layers and anisotropic distribution of inhibition between coronal and horizontal planes. Since deep layers of the GRS receive inputs from the subiculum, GRS circuits may work as an integrator of multiple sources such as sensory and memory information.
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Conrad, Rachel, and Mia C. N. Perez. "Congenital Granular Cell Epulis." Archives of Pathology & Laboratory Medicine 138, no. 1 (January 1, 2014): 128–31. http://dx.doi.org/10.5858/arpa.2012-0306-rs.
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Congenital granular cell epulis is a rarely reported lesion of unknown histogenesis with a strong predilection for the maxillary alveolar ridge of newborn girls. Microscopically, it demonstrates nests of polygonal cells with granular cytoplasm, a prominent capillary network, and attenuated overlying squamous epithelium. The lesion lacks immunoreactivity for S-100, laminin, chromogranin, and most other markers except neuron-specific enolase and vimentin. Through careful observation of its unique clinical, histopathologic, and immunohistochemical features, this lesion can be distinguished from the more common adult granular cell tumor as well as other differential diagnoses.
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Yamamoto, T., R. Matsuo, Y. Kiyomitsu, and R. Kitamura. "Sensory inputs from the oral region to the cerebral cortex in behaving rats: an analysis of unit responses in cortical somatosensory and taste areas during ingestive behavior." Journal of Neurophysiology 60, no. 4 (October 1, 1988): 1303–21. http://dx.doi.org/10.1152/jn.1988.60.4.1303.
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1. The responses of 90 cortical neurons in the somatosensory and gustatory areas were recorded with chronically implanted fine wires in freely moving Wistar rats. The responses were analyzed mainly while the animals were freely licking solutions and eating dry pellets. Cortical neurons were classified into several groups according to their response properties. 2. "Mechanosensitive" neurons (n = 20) showed rhythmic phasic activity in different phases of the licking cycle, depending on the location of their receptive field in the peripheral orofacial region. 3. "Movement-related" neurons (n = 27) changed their activities tonically during licking, chewing, or grooming behavior. The responses were either excitatory or inhibitory. Receptive fields and adequate stimuli could not be identified. These neurons might receive somatosensory (except light tactile) inputs from wide or deep areas of intra- or perioral regions, or might be related to orofacial active movement. 4. "Taste" neurons (n = 35) increased or decreased their discharge rates during licking of particular taste solutions. Some taste neurons received convergence from somatosensory inputs. 5. "Temperature" neurons (n = 2) responded exclusively to water of temperatures lower or higher than room temperature. The responses were opposite in direction between cold and warm stimuli. 6. "Anticipation" neurons (n = 4) increased their impulse discharges before the start of licking in the situation in which the animal expected access to the drinking tube. 7. "Attention" neurons (n = 2) responded to arousal stimulation such as sound, a flash of light, and body touch. These neurons showed only a slightly increasing response during ingestive behavior. 8. The locations of 56 of 90 units were histologically identified. Mechanosensitive neurons were located in the appropriate parts of the somatotopic pattern within the primary somatic sensory area in the granular cortex. Taste neurons were found evenly in the dysgranular cortex and the agranular insular cortex. Other types of neurons were located mainly in the dysgranular cortex between the granular cortex and agranular insular cortex, and some were intermingled with taste neurons in the agranular insular cortex. 9. The present study has shown that cortical neurons in the orolingual somatosensory and taste areas have different response characteristics related to each aspect of ingestive behavior.(ABSTRACT TRUNCATED AT 400 WORDS)
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Zimatkin, S. M., and O. A. Karniushko. "THE SYNAPTOGENESIS IN THE DEVELOPING CEREBELLUM OF THE RAT." Morphology 150, no. 4 (August 15, 2016): 34–39. http://dx.doi.org/10.17816/morph.397734.
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The aim of this study - qualitative and quantitative evaluation of synaptogenesis in the developing cerebellum of the rat (postnatal Days 2-45) using immunohistochemical detection of synaptophysin (SYP) as the the marker. The expression of SYP was demonstrated in postmitotic neurons of the external granular layer and migrating precursors of granular neurons of the cerebellum. During the whole period studied, an increase in the width of the zone of synaptogenesis in the molecular layer took place together with the decrease of SYP-immunoreactivity. The reduction in the number of SYP-immunopositive synapses was noted around Purkinje cell perikarya from Day 7 till Day 15. In the internal granular layer, SYP-immunopositive dots were observed that increased in size from Day 2 to Day 45 due to the formation of cerebellar glomeruli. In the cerebellar interposed nucleus, the number and sizes of axosomatic synapses around neuronal perikarya were found to increase during the whole period examined. In the neuropil, the uneven aggregates of SYP-immunopositive axodendritic synapses were observed.
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Algaidi, Sami A., Magda A. Eldomiaty, Yasser M. Elbastwisy, Shaima M. Almasry, Maha K. Desouky, and Ahmed M. Elnaggar. "Effect of voluntary running on expression of myokines in brains of rats with depression." International Journal of Immunopathology and Pharmacology 33 (January 2019): 205873841983353. http://dx.doi.org/10.1177/2058738419833533.
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This study aimed to demonstrate the histopathology and immunoexpression of exercise-derived myokines in dentate gyrus (DG), medial prefrontal cortex (mPFC) and cerebellum of depressed Wistar rats during depression and after practising voluntary running. Depression was developed by forced swimming for 2 weeks. Voluntary running was performed by voluntary running for 3 weeks. Brain sections were processed and immunostained to detect brain-derived neurotrophic factor (BDNF), macrophage migration inhibitory factor (MIF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6). ImageJ software was used to measure the optical density (OD). BDNF was expressed in neurons in DG, mPFC and granular and Purkinje cells in cerebellum. MIF was expressed in neurons of sub-granular zone in DG, mPFC and Purkinje cells. VEGF was expressed in many neurons in DG, mPFC and Purkinje cells. IL-6 was expressed in some neurons in DG, in neuropil of mPFC and in Purkinje cells. In depression, the OD of studied myokines significantly decreased in all examined areas. After voluntary running, the OD of myokines significantly increased in all areas. This study defines the immunohistochemical expression of myokines in brain areas in depression and after voluntary running and reveals the involvement of the mPFC and cerebellum in the pathophysiology of depression.
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Rissi, Daniel R. "Neuropathology of natural canid alphaherpesvirus 1 infection in dogs." Brazilian Journal of Veterinary Pathology 16, no. 2 (2023): 96–99. http://dx.doi.org/10.24070/bjvp.1983-0246.v16i2p96-99.
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The neuropathology of canid alphaherpesvirus 1 (CaHV-1) infection in dogs has been reported, but the importance of the cerebellar lesions in the routine diagnosis remains relatively understated in the veterinary literature. Here we characterize the neuropathology of natural CaHV-1 infection in 25 dogs. The disease affected predominantly male dogs (22 cases). Clinical signs in 15 cases varied and sudden death was reported in 10 cases. All dogs had the typical areas of necrosis and hemorrhage in multiple organs with eosinophilic intranuclear viral inclusions in epithelial and/or inflammatory cells in multiple organs in 21 cases. Cerebral swelling and reddening were reported in 3 cases. Neurohistologic changes consisted of mild lymphoplasmacytic meningoencephalitis with occasional vasculitis and widespread glial nodules. Rare intranuclear viral inclusions (4 cases) were observed in endothelial cells or inflammatory cells in glial nodules. Cerebellum was examined in 11 cases and had extensive segmental necrosis of Purkinje cell layer (8 cases) and granule neurons in the internal (9 cases) or external (2 cases) granular cell layer. Intranuclear viral inclusions were observed in 8 cases and occurred in necrotic granule neurons in the inner granular cell layer (7 cases), outer granular cell layer (2 cases), Purkinje neurons (1 case), or endothelial cells (1 case). Diagnostic confirmation in 23 cases was based on routine histology and fluorescent antibody testing for CaHV-1 on fresh or frozen tissue samples. A routine diagnosis was based solely on the visualization of intranuclear viral inclusions in 2 cases.
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Cavaliere, Antonio, Angelo Sidoni, Ivana Ferri, and Brunangelo Falini. "Granular Cell Tumor: An Immunohistochemical Study." Tumori Journal 80, no. 3 (June 1994): 224–28. http://dx.doi.org/10.1177/030089169408000312.
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Aims and background Granular cell tumor, usually a benign neoplasm, has been the object of many studies because of its uncertain histogenesis and based on many immunohistochemical and ultrastructural studies it has been suggested that it originates from the Schwann cell. Our recent observation that granular cell tumor is positive with PG-M1, a new anti-macrophage monoclonal antibody, led us to further investigate the immunophenotypic profile of the tumor. Study design We studied 11 granular cell tumors using a panel of 20 antibodies, 13 monoclonal and 7 polyclonal. Results The immunohistochemical study showed in all cases a constant diffuse positivity for S-100 protein, neuron-specific enolase, vimentin, KP1 and PG-M1, as well as occasional and focal positivity for alpha-1-antitrypsin, alpha-1-antichymotrypsin and lysozyme. Conclusions The immunophenotypic profile constantly observed could be the expression, on one hand, of the neuroectodermic nature of the neoplasm, proven by positivity for S-100 protein, neuron specific enolase and vimentin, and on the other could be the expression of the phagocytic activity of the tumor cell, proven by positivity for KP1 and PG-M1 antibodies and also by the presence of numerous phagolysosomes.
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Welle, Cristin G., and Diego Contreras. "Sensory-driven and spontaneous gamma oscillations engage distinct cortical circuitry." Journal of Neurophysiology 115, no. 4 (April 1, 2016): 1821–35. http://dx.doi.org/10.1152/jn.00137.2015.
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Gamma oscillations are a robust component of sensory responses but are also part of the background spontaneous activity of the brain. To determine whether the properties of gamma oscillations in cortex are specific to their mechanism of generation, we compared in mouse visual cortex in vivo the laminar geometry and single-neuron rhythmicity of oscillations produced during sensory representation with those occurring spontaneously in the absence of stimulation. In mouse visual cortex under anesthesia (isoflurane and xylazine), visual stimulation triggered oscillations mainly between 20 and 50 Hz, which, because of their similar functional significance to gamma oscillations in higher mammals, we define here as gamma range. Sensory representation in visual cortex specifically increased gamma oscillation amplitude in the supragranular (L2/3) and granular (L4) layers and strongly entrained putative excitatory and inhibitory neurons in infragranular layers, while spontaneous gamma oscillations were distributed evenly through the cortical depth and primarily entrained putative inhibitory neurons in the infragranular (L5/6) cortical layers. The difference in laminar distribution of gamma oscillations during the two different conditions may result from differences in the source of excitatory input to the cortex. In addition, modulation of superficial gamma oscillation amplitude did not result in a corresponding change in deep-layer oscillations, suggesting that superficial and deep layers of cortex may utilize independent but related networks for gamma generation. These results demonstrate that stimulus-driven gamma oscillations engage cortical circuitry in a manner distinct from spontaneous oscillations and suggest multiple networks for the generation of gamma oscillations in cortex.
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Kishino, Akiyoshi, Chikao Nakayama, Tohru Nakanishi, Nobuyuki Fukushima, and Hiroshi Noguchi. "Monoclonal antibodies specifically recognizing granular structures in hippocampal neurons." Neuroscience Research Supplements 19 (January 1994): S105. http://dx.doi.org/10.1016/0921-8696(94)92559-3.
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Hafner, S., S. Flynn, B. G. Harmon, and J. E. Hill. "Neuronal Ceroid-Lipofuscinosis in a Holstein Steer." Journal of Veterinary Diagnostic Investigation 17, no. 2 (March 2005): 194–97. http://dx.doi.org/10.1177/104063870501700218.
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A young, partially blind Holstein steer was affected by mild cerebral atrophy. Formalin-fixed cerebral gray matter was diffusely yellow brown. Microscopically, there were eosinophilic, autofluorescent granules primarily in the cytoplasm of cerebral neurons. There was also extensive retinal atrophy with complete loss of the rod and cone layers. Ultrastructural examination of affected cerebral neurons revealed a mixture of granular osmiophilic and lamellar patterns in the cytoplasmic storage bodies. This suggests the existence of neuronal ceroid-lipofuscinosis in the Holstein breed.
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Tang, Yuanhong, Lingling An, Quan Wang, and Jian K. Liu. "Regulating synchronous oscillations of cerebellar granule cells by different types of inhibition." PLOS Computational Biology 17, no. 6 (June 28, 2021): e1009163. http://dx.doi.org/10.1371/journal.pcbi.1009163.
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Synchronous oscillations in neural populations are considered being controlled by inhibitory neurons. In the granular layer of the cerebellum, two major types of cells are excitatory granular cells (GCs) and inhibitory Golgi cells (GoCs). GC spatiotemporal dynamics, as the output of the granular layer, is highly regulated by GoCs. However, there are various types of inhibition implemented by GoCs. With inputs from mossy fibers, GCs and GoCs are reciprocally connected to exhibit different network motifs of synaptic connections. From the view of GCs, feedforward inhibition is expressed as the direct input from GoCs excited by mossy fibers, whereas feedback inhibition is from GoCs via GCs themselves. In addition, there are abundant gap junctions between GoCs showing another form of inhibition. It remains unclear how these diverse copies of inhibition regulate neural population oscillation changes. Leveraging a computational model of the granular layer network, we addressed this question to examine the emergence and modulation of network oscillation using different types of inhibition. We show that at the network level, feedback inhibition is crucial to generate neural oscillation. When short-term plasticity was equipped on GoC-GC synapses, oscillations were largely diminished. Robust oscillations can only appear with additional gap junctions. Moreover, there was a substantial level of cross-frequency coupling in oscillation dynamics. Such a coupling was adjusted and strengthened by GoCs through feedback inhibition. Taken together, our results suggest that the cooperation of distinct types of GoC inhibition plays an essential role in regulating synchronous oscillations of the GC population. With GCs as the sole output of the granular network, their oscillation dynamics could potentially enhance the computational capability of downstream neurons.
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Rosso, Renato, Mario Scelsi, and Luciano Carnevali. "Granular Cell Traumatic Neuroma." Archives of Pathology & Laboratory Medicine 124, no. 5 (May 1, 2000): 709–11. http://dx.doi.org/10.5858/2000-124-0709-gctn.
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Abstract Background.—Granular cell changes can be observed in a variety of benign and malignant tumors, and are seen more commonly in granular cell tumors, which in about 5% of cases develop in the breast. Granular cells also have been observed in sites of previous trauma, such as surgery, and are found to be inflammatory reactions of histiocytic origin. Methods and Results.—We investigated, morphologically and immunohistochemically, 2 granular cell lesions occurring in mastectomy scars after surgery for carcinoma. Both lesions were composed of strands and nests of large granular cells, haphazardly set in a background of fibrous tissue, with sparse inflammatory infiltrates. Several tortuous hypertrophic nerve bundles were also embedded in the fibrous tissue. A few of these nerve bundles showed degenerative changes and contained granular cells. Immunohistochemically, granular cells were positive for S100 protein, neuron-specific enolase, vimentin, and CD68 antigen. Conclusions.—We consider these proliferative lesions of peripheral nerves to have the features of both granular cell tumor and traumatic neuroma. These cases indicate that traumatic neuroma can undergo extensive granular cell changes and constitute a previously unrecognized entity, which we provisionally label granular cell traumatic neuroma. Granular cell traumatic neuroma has to be taken into consideration when evaluating lesions occurring at mastectomy scars and should be differentiated from malignant tumors with granular cells, such as apocrine carcinoma and alveolar soft part sarcoma.
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Wallis, Karin, Susi Dudazy, Max van Hogerlinden, Kristina Nordström, Jens Mittag, and Björn Vennström. "The Thyroid Hormone Receptor α1 Protein Is Expressed in Embryonic Postmitotic Neurons and Persists in Most Adult Neurons." Molecular Endocrinology 24, no. 10 (October 1, 2010): 1904–16. http://dx.doi.org/10.1210/me.2010-0175.
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Abstract Thyroid hormone is essential for brain development where it acts mainly through the thyroid hormone receptor α1 (TRα1) isoform. However, the potential for the hormone to act in adult neurons has remained undefined due to difficulties in reliably determining the expression pattern of TR proteins in vivo. We therefore created a mouse strain that expresses TRα1 and green fluorescent protein as a chimeric protein from the Thra locus, allowing examination of TRα1 expression during fetal and postnatal development and in the adult. Furthermore, the use of antibodies against other markers enabled identification of TRα1 expression in subtypes of neurons and during specific stages of their maturation. TRα1 expression was first detected in postmitotic cells of the cortical plate in the embryonic telencephalon and preceded the expression of the mature neuronal protein NeuN. In the cerebellum, TRα1 expression was absent in proliferating cells of the external granular layer, but switched on as the cells migrated towards the internal granular layer. In addition, TRα1 was expressed transiently in developing Purkinje cells, but not in mature cells. Glial expression was found in tanycytes in the hypothalamus and in the cerebellum. In the adult brain, TRα1 expression was detected in essentially all neurons. Our data demonstrate that thyroid hormone, unexpectedly, has the capacity to play an important role in virtually all developing and adult neurons. Because the role of TRα1 in most neuronal cell types in vivo is largely unknown, our findings suggest that novel functions for thyroid hormone remain to be identified in the brain.
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Ishunina, T. A. "Morphological Changes in the Somatosensory Cortex of Guinea Pigs Following Simulation of the Abdominal Surgery Wound." Journal of Anatomy and Histopathology 10, no. 4 (December 16, 2021): 36–42. http://dx.doi.org/10.18499/2225-7357-2021-10-4-36-42.
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The aim of research was to study the effect of the abdominal wall injuries and ascorbic acid (AA) on morphometric parameters of the somatosensory cortex.Material and methods. The density of the arrangement of neurons, sizes of nuclei and perikaryons of neurons, density and area of blood vessels in the somatosensory cortex were detected in guinea pigs after simulation of the abdominal wall injury. The process was accompanied by the parenteral administration of AA.Results. Simulation of the abdominal wall injury in guinea pigs resulted in a decreased thickness of the somatosensory cortex and a decreased density of neurons arrangement (on average by 32-37%). In 7 days after the operation, the exposed animals demonstrated a decreased density of blood vessels by 14–18%, the size of blood vessels also decreased by 27–46%; the fact evidencing a deterioration in the blood supply to the somatosensory cortex in the postoperative period. The effect of AA was mainly manifested in the increased size of the nuclei and perikaryons of neurons (by 20–40%); this evidencing activation of their metabolic activity. The most significant changes in the studied parameters were observed in the outer granular and, to a lesser extent, in the pyramidal and inner granular cytoarchitectonic layers.Conclusion. Experimental abdominal surgical interventions resulted in a decreased size and density of blood vessels in the somatosensory cortex. The results obtained can be used to develop methods of postoperative rehabilitation with the inclusion of drugs that improve blood supply and metabolism of the brain neurons. AA potentiates some of the effects of surgery on the somatosensory cortex; currently, there are no sufficient data to recommend it as a neuroprotective agent in the postoperative period.
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Quach, Tam, Nathalie Auvergnon, Rajesh Khanna, Marie-Françoise Belin, Papachan Kolattukudy, Jérome Honnorat, and Anne-Marie Duchemin. "Opposing Morphogenetic Defects on Dendrites and Mossy Fibers of Dentate Granular Neurons in CRMP3-Deficient Mice." Brain Sciences 8, no. 11 (November 3, 2018): 196. http://dx.doi.org/10.3390/brainsci8110196.
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Collapsin response mediator proteins (CRMPs) are highly expressed in the brain during early postnatal development and continue to be present in specific regions into adulthood, especially in areas with extensive neuronal plasticity including the hippocampus. They are found in the axons and dendrites of neurons wherein they contribute to specific signaling mechanisms involved in the regulation of axonal and dendritic development/maintenance. We previously identified CRMP3’s role on the morphology of hippocampal CA1 pyramidal dendrites and hippocampus-dependent functions. Our focus here was to further analyze its role in the dentate gyrus where it is highly expressed during development and in adults. On the basis of our new findings, it appears that CRMP3 has critical roles both in axonal and dendritic morphogenesis of dentate granular neurons. In CRMP3-deficient mice, the dendrites become dystrophic while the infrapyramidal bundle of the mossy fiber shows aberrant extension into the stratum oriens of CA3. This axonal misguided projection of granular neurons suggests that the mossy fiber-CA3 synaptic transmission, important for the evoked propagation of the activity of the hippocampal trisynaptic circuitry, may be altered, whereas the dystrophic dendrites may impair the dynamic interactions with the entorhinal cortex, both expected to affect hippocampal function.
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Gil, Laura, Erika Chi-Ahumada, Sandra A. Niño, Gabriela Capdeville, Areli M. Méndez-Torres, Carmen Guerrero, Ana B. Rebolledo, Isabel M. Olazabal, and María E. Jiménez-Capdeville. "Pathological Nuclear Hallmarks in Dentate Granule Cells of Alzheimer’s Patients: A Biphasic Regulation of Neurogenesis." International Journal of Molecular Sciences 23, no. 21 (October 25, 2022): 12873. http://dx.doi.org/10.3390/ijms232112873.
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The dentate gyrus (DG) of the human hippocampus is a complex and dynamic structure harboring mature and immature granular neurons in diverse proliferative states. While most mammals show persistent neurogenesis through adulthood, human neurogenesis is still under debate. We found nuclear alterations in granular cells in autopsied human brains, detected by immunohistochemistry. These alterations differ from those reported in pyramidal neurons of the hippocampal circuit. Aging and early AD chromatin were clearly differentiated by the increased epigenetic markers H3K9me3 (heterochromatin suppressive mark) and H3K4me3 (transcriptional euchromatin mark). At early AD stages, lamin B2 was redistributed to the nucleoplasm, indicating cell-cycle reactivation, probably induced by hippocampal nuclear pathology. At intermediate and late AD stages, higher lamin B2 immunopositivity in the perinucleus suggests fewer immature neurons, less neurogenesis, and fewer adaptation resources to environmental factors. In addition, senile samples showed increased nuclear Tau interacting with aged chromatin, likely favoring DNA repair and maintaining genomic stability. However, at late AD stages, the progressive disappearance of phosphorylated Tau forms in the nucleus, increased chromatin disorganization, and increased nuclear autophagy support a model of biphasic neurogenesis in AD. Therefore, designing therapies to alleviate the neuronal nuclear pathology might be the only pathway to a true rejuvenation of brain circuits.
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Sarnat, Harvey B. "8. Maturation of the Fetal Olfactory Bulb." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 42, S2 (August 2015): S4. http://dx.doi.org/10.1017/cjn.2015.256.
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The olfactory bulb exhibits architecture unique amongst laminar cortices, lacking molecular and subplate zones and having superficial synaptic glomeruli. Its ontogenesis also is unique because neuroblasts do not migrate radially but stream in from the rostral telencephalon; an ependymal-lined olfactory ventricle is transitory. The olfactory is the only sensory system to not project to the thalamus but incorporates a thalamic equivalent. It is a repository of progenitor cells in the mature brain. The aim was to define olfactory bulb development in the human foetus: synaptogenesis and cellular maturation.Immunoreactivity in paraffin sections of synaptophysin, NeuN, calretinin, vimentin and nestin was examined at autopsy in olfactory bulb in 20 foetuses, 9-40wks gestation. Synaptophysin reactivity was seen around the somata of mitral and tufted neurons at 9wks, synaptic glomeruli at 13wks. The granule cell layer in the core exhibited NeuN-reactive nuclei in cells of the outer half at 20wks; 60% of granular neurons reacted by term. Synaptophysin reactivity in the granular layer initiates at 15wk. GABAergic calretinin-reactive neurons and neurites and synaptic glomeruli appeared at 13wks. Nestin- and vimentin-reactive bipolar progenitor cells were shown at all gestational ages, mainly in the granular layer, the ratio to other cells remaining constant. Synapses form in the small accessory olfactory bulb of the nervus terminalis earlier than in the main bulb. Development of synaptic vesicles in the human fetal olfactory bulb is precise both spatially and temporally, but not yet fully mature at term.In brain malformations and congenital metabolic and genetic diseases, the olfactory bulb may be affected and provide additional neuropathological data. Therapeutic autologous transplantation of olfactory progenitor cells focus renewed interest in the olfactory bulb.
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Guyon, Alice, and Jean-Louis Nahon. "Multiple actions of the chemokine stromal cell-derived factor-1α on neuronal activity." Journal of Molecular Endocrinology 38, no. 3 (March 2007): 365–76. http://dx.doi.org/10.1677/jme-06-0013.
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The chemokine SDF-1α and its cognate receptor CXCR4 are expressed in several neuronal populations. This review focuses on our current knowledge about the actions of this chemokine on neuronal excitability, through CXCR4 or other yet unknown pathways. In various neuronal populations (CA1 neurons of the hippocampus, granular and Purkinje cells of the cerebellum, melanin-concentrating hormone neurons of the lateral hypothalamus, vasopressinergic neurons of the supraoptic and the paraventricular nucleus of the hypothalamus, and dopaminergic neurons of the substantia nigra), SDF-1α can modulate the activity of neurons by multiple regulatory pathways including and often combining: (i) modulation of voltage-dependent channels (sodium, potassium, and calcium), (ii) activation of the G-protein-activated inward rectifier potassium current, and (iii) increase in neurotransmitter release (gamma-amino butyric acid (GABA), glutamate, and dopamine), often through Ca-dependent mechanisms. The possible mechanisms underlying these effects and their consequences in terms of modulation of neuroendocrine systems and physiopathology are discussed.
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Bulyk, R., V. Yosypenko, M. Kryvchanska, K. Vlasova, and Y. Lukan. "Age changes in the tigroid substance of neutrons of the lateral preoptic nucleus of hypothalamus under different light modes." Journal of Education, Health and Sport 11, no. 10 (October 29, 2021): 269–74. http://dx.doi.org/10.12775/jehs.2021.11.10.025.
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The article presents analysis of the results of the original histochemical studies of tigroid substance of neurons of the lateral preoptic nucleus of hypothalamus in mature and old rats under the influence of different light modes. In all observations, the tigroid substance was located in the cytoplasm of neurons of the lateral preoptic nucleus of hypothalamus in the form of individual granular formations of different sizes and shapes. The amount of tigroid substance of neurons of the lateral preoptic nucleus of hypothalamus in mature rats is greater than in older rats. At the same time, it should be noted that different experimental conditions significantly affected the amount of tigroid substance in neurons of the lateral preoptic nucleus of hypothalamus in old rats. In particular, under conditions of light deprivation, the optical density of specific histochemical staining for tigroid substance in neurons of the lateral preoptic nucleus of hypothalamus increased significantly (p<0,001), and under conditions of light stimulation, on the contrary, probably decreased (p<0,001).
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Krakowska, Izabela, and Grzegorz Lonc. "Expression of Progesterone Receptors in Hippocampal Neurons in Rabbit Males." Bulletin of the Veterinary Institute in Pulawy 56, no. 2 (June 1, 2012): 231–34. http://dx.doi.org/10.2478/v10213-012-0041-1.
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Abstract The aim of this study was to investigate the presence of progesterone receptors in hippocampal neurons of male rabbits and the distribution of these receptors in different areas of the hippocampus. The examinations were carried out on brains of five males, New Zealand breed, age of 2 years, weighing 2-3 kg. Immunohistochemical detection of receptors was performed using DAKO LSAB + Kit Peroxidase method. The sections were incubated with primary monoclonal antibody for progesterone receptor NCL-LPGR- AB. The obtained results have shown the presence of progesterone receptors in neurons of CA1, CA3, and CA4 regions of the hippocampus. The reaction also occurred in the region of granular cells of the dental gyrus. The reaction was seen in the cytoplasm and nuclei of neurons simultaneously, whereas some neurons did not show any reaction in the nucleus and cytoplasm. Occurrence of progesterone receptors in most neurons of the hippocampus confirms a direct influence of progesterone on the hippocampus and its functions in rabbit males.
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Rosario, C. M., B. D. Yandava, B. Kosaras, D. Zurakowski, R. L. Sidman, and E. Y. Snyder. "Differentiation of engrafted multipotent neural progenitors towards replacement of missing granule neurons in meander tail cerebellum may help determine the locus of mutant gene action." Development 124, no. 21 (November 1, 1997): 4213–24. http://dx.doi.org/10.1242/dev.124.21.4213.
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Previously we observed that stable clones of multipotent neural progenitor cells, initially isolated and propagated from the external granular layer of newborn wild-type mouse cerebellum, could participate appropriately in cerebellar development when reimplanted into the external granular layer of normal mice. Donor cells could reintegrate and differentiate into neurons (including granule cells) and/or glia consistent with their site of engraftment. These findings suggested that progenitors might be useful for cellular replacement in models of aberrant neural development or neurodegeneration. We tested this hypothesis by implanting clonally related multipotent progenitors into the external granular layer of newborn meander tail mice (gene symbol=mea). mea is an autosomal recessive mutation characterized principally by the failure of granule cells to develop in the cerebellar anterior lobe; the mechanism is unknown. We report that approximately 75% of progenitors transplanted into the granuloprival anterior lobe of neonatal mea mutants differentiated into granule cells, partially replacing or augmenting that largely absent neuronal population in the internal granular layer of the mature meander tail anterior lobe. (The ostensibly ‘normal’ meander tail posterior lobe also benefited from repletion of a more subtle granule cell deficiency.) Donor-derived neurons were well-integrated within the neuropil, suggesting that these progenitors' developmental programs for granule cell differentiation were unperturbed. These observations permitted several conclusions. (1) That exogenous progenitors could survive transplantation into affected regions of neonatal meander tail cerebellum and differentiate into the deficient cell type suggested that the microenvironment was not inimical to granule cell development. Rather it suggested that mea's deleterious action is intrinsic to the external granular layer cell. (Any cell-extrinsic actions--albeit unlikely--had to be restricted to readily circumventable prenatal events.) This study, therefore, offers a paradigm for using progenitors to help determine the site of action of other mutant genes or to test hypotheses regarding the pathophysiology underlying other anomalies. (2) In the regions most deficient in neurons, a neuronal phenotype was pursued in preference to other potential cell types, suggesting a ‘push’ of undifferentiated, multipotent progenitors towards compensation for granule cell dearth. These data suggested that progenitors with the potential for multiple fates might differentiate towards repletion of deficient cell types, a possible developmental mechanism with therapeutic implications. Neural progenitors (donor or endogenous) might enable cell replacement in some developmental or degenerative diseases--most obviously in cases where a defect is intrinsic to the diseased cell, but also, under certain circumstances, when extrinsic pathologic forces may exist.
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Idzhilova, O. S., N. A. Simonova, M. G. Minlebaev, and A. Yu Malyshev. "Infragranular excitatory projection to granular neurons in neonatal rodent somatosensory neocortex." Genes & Cells 18, no. 4 (December 15, 2023): 771–73. http://dx.doi.org/10.17816/gc623337.
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Though the principles of central nervous system development are genetically encoded, the cortical activity is also critically involved in these processes. While this question is quite important, up to now we are limited in our understanding of the role that neuronal activity plays in formation of functionally linked cellular ensembles in the developing cortex. Recently, transient inhibitory neuronal projections were shown in the barrel cortex during the critical period of its development. Expression of interneuronal connections from infragranular to other cortical layers exactly during the period of barrel formation suggests their critical role in establishment of adult-like columnar organization of the barrel cortex. While the inhibitory connections were demonstrated, the question remains, whether the transient connectivity is restricted by emergence of inhibitory projections, or both types (including excitatory connections) could be expressed during the critical period of the barrel cortex development. Here, we aimed to answer this question using in vitro optogenetic stimulation of the neurons in the infragranular layers of the neonatal mouse barrel cortex. A viral vector of serotype AAV.PHP.eB containing channelrhodopsin-2 along with a fluorescent Venus tag sequence under the hSyn promoter was delivered via intraventricular injection into the neonatal mouse brain at P0. This transduction protocol resulted in neuron-specific expression of the construct primarily in the L2/3, L5 and L6 cortical layers at P7. At P7, acute coronal brain slices containing the barrel cortical field were prepared. For a given cortical column, the infragranular layers were optogenetically mapped while simultaneous whole-cell electrophysiological registration of a pyramidal cell in the barrel was performed. Holding potential was varied to discriminate between light-evoked EPSCs and IPSCs. The results of our preliminary recordings in the neonatal somatosensory cortex showed presence of neuronal projections from infra- to granular layer, which is in agreement with the already demonstrated data. However, L4 EPSCs evoked by infragranular layer stimulation were also recorded, suggesting the expression of the excitatory connections from infra- to granular layers early in development. Though we require to continue our recordings, our findings suggest an even more complex network interactions that shape the barrel cortex L4 during the early postnatal stages.
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Hasse, J. Michael, and Farran Briggs. "Corticogeniculate feedback sharpens the temporal precision and spatial resolution of visual signals in the ferret." Proceedings of the National Academy of Sciences 114, no. 30 (July 11, 2017): E6222—E6230. http://dx.doi.org/10.1073/pnas.1704524114.
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The corticogeniculate (CG) pathway connects the visual cortex with the visual thalamus (LGN) in the feedback direction and enables the cortex to directly influence its own input. Despite numerous investigations, the role of this feedback circuit in visual perception remained elusive. To probe the function of CG feedback in a causal manner, we selectively and reversibly manipulated the activity of CG neurons in anesthetized ferrets in vivo using a combined viral-infection and optogenetics approach to drive expression of channelrhodopsin2 (ChR2) in CG neurons. We observed significant increases in temporal precision and spatial resolution of LGN neuronal responses to drifting grating and white noise stimuli when CG neurons expressing ChR2 were light activated. Enhancing CG feedback reduced visually evoked response latencies, increased spike-timing precision, and reduced classical receptive field size. Increased precision among LGN neurons led to increased spike-timing precision among granular layer V1 neurons as well. Together, our findings suggest that the function of CG feedback is to control the timing and precision of thalamic responses to incoming visual signals.
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Kim, Namsuk, Dario Acampora, Florent Dingli, Damarys Loew, Antonio Simeone, Alain Prochiantz, and Ariel A. Di Nardo. "Immunoprecipitation and mass spectrometry identify non-cell autonomous Otx2 homeoprotein in the granular and supragranular layers of mouse visual cortex." F1000Research 3 (July 30, 2014): 178. http://dx.doi.org/10.12688/f1000research.4869.1.
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Plasticity in the visual cerebral cortex is regulated by the internalization of Otx2 homeoprotein into parvalbumin neurons in cortical layers II/III and IV. However the Otx2 locus is not active in these neurons and the protein is imported from external sources, including the choroid plexus. Because Otx1 and Otx2 may have redundant functions, we wanted to verify if part of the staining in parvalbumin neurons corresponds to Otx1 transported from cortical layer V neurons. It is demonstrated here that Otx staining in layer IV cells is maintained in Otx1-null mice. The immunoprecipitation of extracts from finely dissected granular and supragranular cortex (layers I-IV) gave immunoblots with a band corresponding to Otx2 and not Otx1. Moreover, high-resolution mass spectrometry analysis after immunoprecipitation identifies two peptides within the Otx2 homeodomain. One of these peptides is specific for Otx2 and is not found in Otx1. These results unambiguously establish that the staining in parvalbumin neurons revealed with the anti-Otx2 antibodies used in our previous studies identifies non-cell autonomous Otx2.
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Artuković, Branka, Andrea Gudan Kurilj, Ivana Mihoković Buhin, Lidija Medven Zagradišnik, Ivan-Conrado Šoštarić-Zuckermann, and Marko Hohšteter. "Granular cell tumor in the central nervous system of a ferret (Mustela putorius furo) - a case report." Veterinarski arhiv 92, no. 2 (April 29, 2022): 205–12. http://dx.doi.org/10.24099/vet.arhiv.1705.
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A granular cell tumor (GCT) in the central nervous system (CNS) of a ferret is a rare finding. In this case a cerebral GCT is described in a 5-year-old castrated female ferret. The animal developed lameness in right hind leg which progreseed to total ataxia. The animal died and a necropsy revealed the mass in the medial to caudal part of the left frontal lobe of the brain. Based on histological and imunohistochemical findings, tumor was diagnosed as granular cell tumor. Immunohistochemically, granular cells were diffusely positive for vimentin and neuron-specific enolase (NSE) and weakly focal reactivity for S-100 protein was seen. Neoplastic cells did not express cytokeratins and glial fibrillary acidic protein (GFAP). Although immunohistochemistry was performed, histogenesis of this tumor remains unsolved and controversial.
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Kawaida, Masahiro, Hiroyuki Fukuda, and Naoyuki Kohno. "Granular Cell Tumors Arising Nearly Simultaneously in the Larynx and Subcutaneous Cervical Region." Ear, Nose & Throat Journal 79, no. 3 (March 2000): 162–66. http://dx.doi.org/10.1177/014556130007900309.
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Granular cell tumors are benign, relatively rare lesions that can occur in any organ in the body. Tumors are known to occasionally arise in two or more different organs. We report the case of a 60-year-old woman in whom granular cell tumors arose almost simultaneously in her subcutaneous cervical region and her larynx. The two tumors were surgically resected and examined histopathologically, and they exhibited the same histopathologic features. The tumor of the larynx was resected with the help of a carbon dioxide laser. Immunohistochemical staining revealed that both were positive for S-100 protein and neuron-specific enolase. Cases of the nearly simultaneous appearance of granular cell tumors in the neck and larynx are rather unusual. The results of immunohistochemical staining suggested that this tumor originates in nerve tissue.
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Chuong, C. M., K. L. Crossin, and G. M. Edelman. "Sequential expression and differential function of multiple adhesion molecules during the formation of cerebellar cortical layers." Journal of Cell Biology 104, no. 2 (February 1, 1987): 331–42. http://dx.doi.org/10.1083/jcb.104.2.331.
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We have correlated the times of appearance of the neural cell adhesion molecule (N-CAM), the neuron-glia cell adhesion molecule (Ng-CAM), and the extracellular matrix protein, cytotactin, during the development of the chicken cerebellar cortex, and have shown that these molecules make different functional contributions to granule cell migration. Immunofluorescent staining showed distinct spatiotemporal expression sequences for each adhesion molecule. N-CAM was present at all times in all layers. However, the large cytoplasmic domain polypeptide of N-CAM was always absent from the external granular layer and was enriched in the molecular layer as development proceeded. Ng-CAM began to be expressed in the premigratory granule cells just before migration and later disappeared from cell bodies but remained on parallel fibers. Cytotactin, which is synthesized by glia and not by neurons, appeared first in a speckled pattern within the external granular layer and later appeared in a continuous pattern along the Bergmann glia; it was also enriched in the molecular layer. After we established their order of appearance, we tested the separate functions of these adhesion molecules in granule cell migration by adding specific antibodies against each molecule to cerebellar explant cultures that had been labeled with tritiated thymidine and then measuring the differential distribution of labeled cells in the forming layers. Anti-N-CAM showed marginal effects. In contrast, anti-Ng-CAM arrested most cells in the external granular layer, while anti-cytotactin arrested most cells in the molecular layer. Time course analyses combined with sequential addition of different antibodies in different orders showed that anti-Ng-CAM had a major effect in the early period (first 36 h in culture) and a lesser effect in the second part of the culture period, while anti-cytotactin had essentially no effect at the earlier time but had major effects at a later period (18-72 h in culture). The two major stages of cerebellar granule cell migration thus appear to be differentially affected by distinct adhesion molecules of different cellular origins, binding mechanisms, and overall distributions. The results indicated that local cell surface modulation of adhesion molecules of different specificities at defined stages and sites is essential to the formation of cerebellar cortical layers.
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Ignatova, A. M., and M. A. Zemlyanova. "BIOLOGICAL ASSESSMENT OF THE IMPACT OF ALUMINUM OXIDE MICROAND NANOPARTICLES ON THE ORGANISM OF LABORATORY ANIMALS IN CONDITIONS OF ACUTE TOXICITY." Toxicological Review, no. 3 (June 24, 2020): 33–40. http://dx.doi.org/10.36946/0869-7922-2020-3-33-40.
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Aluminum oxide nanoparticles widely used in the production are part of many consumer goods, such as pharmaceuticals, food additives etc. The study of the biological hazard of aluminum oxide is of greatest relevance to other aluminum compounds, and the increasing demand for aluminum oxide nanomaterials emphasizes the need to identify specific mechanisms of action of its nanoparticles in comparison with larger micro-sized analogues. It has been found that a specific response from the nervous system to a single intragastric injection of aluminum oxide nanoparticles was a change in the morphometric parameters of the neurons of the granular layer and basket neurons of the molecular layer of the cerebellum of the brain, so the size of the neurons of the granular layer of the cerebellum in rats increases by 1,2 times and the size of the basket neurons of the molecular layer of the cerebellum in rats decreases by 1,1 times relative to similar indicators when exposed to microparticles. In case of intragastric administration of the aluminum oxide nanoparticles, the blood filling of sinusoid spaces of liver tissues, thrombosis progressing without visible compensatory changes, and damage to the nuclei of hepatocytes occur in comparison to an increase in the proportion of sinusoid spaces of liver tissues without a sharp increase in blood accumulations and apoptosis of hepatocytes at the level of 3% specific to the injection of aluminum oxide microparticles. The nature of the liver tissue reaction depends on the total specific surface area of the active particles: when exceeding the value of 80 m2, reactions specific for the action of nanoparticles are manifested.