Dissertations / Theses on the topic 'Mouse brain'
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1
Gutierrez, Barragan Daniel. "Brain-wide mapping of fMRI network dynamics in the mouse brain." Doctoral thesis, Università degli studi di Trento, 2018. http://hdl.handle.net/11572/301211.
Full textAbstract:
Intrinsic brain activity has been widely characterized using the blood-oxygen-level-dependent(BOLD) functional Magnetic Resonance Imaging(fMRI)at rest. There is increasing interest in finding reproducible and robust signatures of large-scale brain synchronization, and pinpointing their neurophysiological substrates and inherent alteration in disease.In this respect, the implementation of dynamic fMRI mapping in laboratory animalsrepresents a major advance, offeringthe opportunity to unravel the elusive drivers of this phenomenon via the use of cell-type specific manipulations that are off limits in humans.Multiple investigations have shown that spontaneous brain activity is non-stationary andinvolves reconfigurationsinto multiple dynamicstates.This research describesa series of studies aimedto map spontaneous fMRI (rsfMRI) network dynamics in the resting mouse brain with voxel resolution. Starting from a proof-of-concept demonstration that canonical resting state fMRI correlations are reliably described by brief instances of regional peak fMRI activity, wedevised a novel frame-wise clustering strategy that allowed us to map recurrent fMRI networks states dynamicsin the mouse brain. We showthat brain-wide patterns of fMRI co-activation can be reliably mapped at the group and subject level, defining a restricted set of recurring brain states characterized by rich network structure. Of particular interest was the observation of opposite co-activation of the mouse default mode network (DMN) and Latero-cortical networks(LCN), two systems that have been proposed to parallel analogous systems of the human brain.Importantly, we also document that these functional states are characterized by contrasting patterns of spontaneous fMRI activity,and exhibit coupled oscillatory dynamics embedded in a common temporal reference marked by infra-slow global fMRI signal oscillations. We next applied this novel framework to a genetic modelof autismand show that aberrant patterns of fMRI connectivity in a genetic model of autism reflect the engagement non-canonical brain states, characterized by altered regional topography and oscillatory dynamics. We finally show that pharmacological stimulation of the cholinergic systems results in reduced large-scale brain synchronization, a finding associated with anew set of oscillating statesin which the involvement of basal forebrain areas is pre-dominant. Collectively,our result demonstrate the possibility of mapping spatio-temporal dynamics of spontaneous brain activity in the living mouse brain with voxel resolution. Our approach reveals a new set of fundamental principles guiding the spatiotemporal organization of resting state fMRI activity, and its disruption in brain disorders.
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Gutierrez, Barragan Daniel. "Brain-wide mapping of fMRI network dynamics in the mouse brain." Doctoral thesis, Università degli studi di Trento, 2018. http://hdl.handle.net/11572/301211.
Full textAbstract:
Intrinsic brain activity has been widely characterized using the blood-oxygen-level-dependent(BOLD) functional Magnetic Resonance Imaging(fMRI)at rest. There is increasing interest in finding reproducible and robust signatures of large-scale brain synchronization, and pinpointing their neurophysiological substrates and inherent alteration in disease.In this respect, the implementation of dynamic fMRI mapping in laboratory animalsrepresents a major advance, offeringthe opportunity to unravel the elusive drivers of this phenomenon via the use of cell-type specific manipulations that are off limits in humans.Multiple investigations have shown that spontaneous brain activity is non-stationary andinvolves reconfigurationsinto multiple dynamicstates.This research describesa series of studies aimedto map spontaneous fMRI (rsfMRI) network dynamics in the resting mouse brain with voxel resolution. Starting from a proof-of-concept demonstration that canonical resting state fMRI correlations are reliably described by brief instances of regional peak fMRI activity, wedevised a novel frame-wise clustering strategy that allowed us to map recurrent fMRI networks states dynamicsin the mouse brain. We showthat brain-wide patterns of fMRI co-activation can be reliably mapped at the group and subject level, defining a restricted set of recurring brain states characterized by rich network structure. Of particular interest was the observation of opposite co-activation of the mouse default mode network (DMN) and Latero-cortical networks(LCN), two systems that have been proposed to parallel analogous systems of the human brain.Importantly, we also document that these functional states are characterized by contrasting patterns of spontaneous fMRI activity,and exhibit coupled oscillatory dynamics embedded in a common temporal reference marked by infra-slow global fMRI signal oscillations. We next applied this novel framework to a genetic modelof autismand show that aberrant patterns of fMRI connectivity in a genetic model of autism reflect the engagement non-canonical brain states, characterized by altered regional topography and oscillatory dynamics. We finally show that pharmacological stimulation of the cholinergic systems results in reduced large-scale brain synchronization, a finding associated with anew set of oscillating statesin which the involvement of basal forebrain areas is pre-dominant. Collectively,our result demonstrate the possibility of mapping spatio-temporal dynamics of spontaneous brain activity in the living mouse brain with voxel resolution. Our approach reveals a new set of fundamental principles guiding the spatiotemporal organization of resting state fMRI activity, and its disruption in brain disorders.
3
Pal, A. (Arup). "Hybrid head cap for mouse brain studies." Master's thesis, University of Oulu, 2019. http://jultika.oulu.fi/Record/nbnfioulu-201909252929.
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Abstract. In this thesis, I present a hybrid head cap in combination with non-invasive multi-channel Electroencephalogram (EEG) and Near-Infrared Spectroscopy (NIRS) to measure brainwaves on mice’s scalps. Laboratory animal research provides insights into multiple potential applications involving humans and other animals. An experimental framework that targets laboratory animals can lead to useful transnational research if it strongly reflects the actual application environment. The non-invasive head cap with three electrodes for EEG and two optodes for NIRS is suggested to measure brainwaves throughout the laboratory mice’s entire brain region without surgical procedures. The suggested hybrid head cap aims to ensure stability in vivo monitoring for mouse brain in a non-invasive way, similarly as the monitoring is performed for the human brain. The experimental part of the work to study the quality of the gathered EEG and fNIRS signals, and usability validation of the head cap, however, was not completed in the planned time frame of the thesis work.
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Kiebish, Michael Andrew. "Mitochondrial lipidome and genome alterations in mouse brain and experimental brain tumors." Thesis, Boston College, 2008. http://hdl.handle.net/2345/27.
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Thesis advisor: Thomas N. SeyfriedMitochondria are the key regulators of the bioenergetic state of the cell. Damage to mitochondrial protein, DNA, or membrane lipids can result as the cause or affect of disease pathology. Regardless, this damage can impair mitochondrial function resulting in a decreased ability to produce ATP to support cellular viability. This thesis research examined the mitochondrial lipidome by shotgun lipidomics in different populations of C57BL/6J (B6) brain mitochondria (non-synaptic and synaptic) and correlated lipid changes to differences in electron transport chain (ETC) activities. Furthermore, a comparison was made for non-synaptic mitochondria between the B6 and the VM mouse strain. The VM strain has a 1.5% incidence of spontaneous brain tumors, which is 210 fold greater than the B6 strain. I determined that differences in the brain mitochondrial lipidome existed in the VM strain compared to the B6 strain, likely corresponding to an increased rate of spontaneous brain tumor formation. Analysis of the mitochondrial genome in the CT-2A, EPEN, VM-NM1, and VM-M3 brain tumors compared to their syngeneic controls mouse strains, C57BL/6J (B6) and VM mice, was examined to determine if mutations existed in experimental brain cancer models. No pathogenic mtDNA mutations were discovered that would likely cause a decrease in the mitochondrial functionality. A novel hypothesis was devised to examine the tumor mitochondrial lipidome to determine if quantitative or molecular species differences existed that could potentially alter the functionality of the ETC. Brain tumor mitochondria were examined from tumors grown in vivo as well as in vitro. Numerous lipid differences were found in the mitochondria of brain tumors, of which the most interesting involved the unique molecular speciation of cardiolipin. ETC activities were significantly decreased in the primary ETC complexes which contribute protons to the gradient as well as the linked complexes of brain tumor mitochondria compared to controls. Taken together, it is likely that differences in the mitochondrial lipidome of brain tumors results in severe impairment of the mitochondria’s ability to produce ATP through the ETC. This research has provided a new understanding of the role of mitochondrial lipids in brain as well as brain cancer and offers an alternative explanation for metabolic dysfunction in cancer
Thesis (PhD) — Boston College, 2008
Submitted to: Boston College. Graduate School of Arts and Sciences
Discipline: Biology
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Malak, Ramez. "2D gel analysis on CNP-overexpressing mouse brain." Thesis, McGill University, 2002. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=79041.
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2',3'-Cyclic nucleotide 3 '-phosphodiesterase (CNP) is an early marker for oligodendrocytes, and it is suspected to be implicated in the expansion of membranes during myelination. We have previously generated transgenic mice that overexpress CNP. These mice showed altered oligodendroyte development, produced aberrant myelination, and had less MBP accumulated in myelin. More interestingly, ODCs isolated from those mice had a tremendous increase in the process extension formation. The purpose of the present study is to compare the protein expression pattern in the myelin isolated from control and CNP overexpressing mice (L191), using two-dimensional gel electrophoresis. We found that CNP overexpression increases HSC70, and HSP70, and decreases MAG expression in myelin. We also found that the mRNA for MAG, in L191 brain was identical to control brain during all stages of development. These findings suggest that CNP may be implicated with HSC70 in vesicular transport, and this may explain the mechanism of process extension mediated by CNP.
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Sawiak, Stephen John. "Computational methods for mouse brain phenotyping using MRI." Thesis, University of Cambridge, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.611550.
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Niranjan, A. "Functional magnetic resonance imaging of the mouse brain." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1543368/.
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Functional magnetic resonance imaging (fMRI) measuring a blood-oxygen-level dependent (BOLD) signal is the most commonly used neuroimaging tool to understand brain function in humans. As mouse models are one of the most commonly used neuroscience experimental models, and with the advent of transgenic mouse models of neurodegenerative pathologies, there has been an increasing push in recent years to apply fMRI techniques to the mouse brain. This thesis focuses on the development and implementation of mouse brain fMRI techniques, in particular to describe the mouse visual system. Multiple studies in the literature have noted several technical challenges in mouse fMRI. In this work I have developed methods which go some way to reducing the impact of these issues, and I record robust and reliable haemodynamic-driven signal responses to visual stimuli in mouse brain regions specific to visual processing. I then developed increasingly complex visual stimuli, approaching the level of complexity used in electrophysiology studies of the mouse visual system, despite the geometric and magnetic field constraints of using a 9.4T pre-clinical MRI scanner. I have also applied a novel technique for measuring high-temporal resolution BOLD responses in the mouse superior colliculus, and I used this data to improve statistical parametric mapping of mouse brain BOLD responses. I also describe the first application of dynamic causal modelling to mouse fMRI data, characterising effective connectivity in the mouse brain visual system. This thesis makes significant contributions to the reverse translation of fMRI to the mouse brain, closing the gap between invasive electrophysiological measurements in the mouse brain and non-invasive fMRI measurements in the human brain.
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Pagani, Marco. "Gray matter covariance networks in the mouse brain." Doctoral thesis, Università degli studi di Trento, 2017. https://hdl.handle.net/11572/368511.
Full textAbstract:
The presence of networks of correlation between gray matter volumes of brain regions - as measured across subjects in a group of individuals - has been consistently described in several human studies, an approach termed structural covariance MRI (scMRI). Complementary to prevalent brain connectivity modalities like functional and diffusion-weighted imaging, this approach can provide valuable insight into the mutual influence of regional trophic and plastic processes occurring between brain regions.
Previous investigations highlighted coordinated growth of these regions within specific structural networks in healthy populations and described their derangement in pathological states. However, a number of fundamental questions about the origin and significance of these couplings remains open and the mechanisms behind the formation of scMRI networks are still poorly understood. To investigate whether analogous scMRI networks are present in lower mammal species amenable to genetic and experimental manipulation such as the laboratory mouse, I coupled high resolution morpho-anatomical MRI with network-based approaches on a large cohort of genetically-homogeneous wild-type mice (C57Bl6/J). To this purpose, I first developed a semi-automated pipeline enabling reliable Voxel Based Morphometry (VBM) of gray matter volumes in the mouse. To validate this approach and its ability to detect plastic changes in brain structures, I applied it to a cohort of aged mice treated with omega-3 polyunsaturated fatty acids (n3-PUFA). This study revealed that treatment with n3PUFA, but not isocaloric olive oil preserved gray matter volume of the hippocampus and frontal cortices, an effect coincident with amelioration of hippocampal-based spatial memory functions. I next employed VBM to investigate scMRI networks in inbred mice using a seed-based approach. In striking resemblance with human findings, I observed the presence of homotopic (i.e. bilateral) architecture in several scMRI cortical and subcortical networks, a finding corroborated by Independent Component Analyses. Subcortical structures also showed highly symmetric inter-hemispheric correlations, with evidence of distributed antero-posterior networks in diencephalic regions of the thalamus and hypothalamus. Hierarchical cluster analysis revealed six identifiable clusters of cortical and sub-cortical regions corresponding to previously described neuroanatomical systems. This work documents for the first time the presence of homotopic cortical and subcortical scMRI networks in the mouse brain, and is poised to pave the way to translational use of this species to investigate the elusive biological and neuroanatomical underpinnings of scMRI network development and its derangement in neuropathological states.
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Pagani, Marco. "Gray matter covariance networks in the mouse brain." Doctoral thesis, University of Trento, 2017. http://eprints-phd.biblio.unitn.it/1916/1/PhD_Thesis_Marco_Pagani.pdf.
Full textAbstract:
The presence of networks of correlation between gray matter volumes of brain regions - as measured across subjects in a group of individuals - has been consistently described in several human studies, an approach termed structural covariance MRI (scMRI). Complementary to prevalent brain connectivity modalities like functional and diffusion-weighted imaging, this approach can provide valuable insight into the mutual influence of regional trophic and plastic processes occurring between brain regions.
Previous investigations highlighted coordinated growth of these regions within specific structural networks in healthy populations and described their derangement in pathological states. However, a number of fundamental questions about the origin and significance of these couplings remains open and the mechanisms behind the formation of scMRI networks are still poorly understood. To investigate whether analogous scMRI networks are present in lower mammal species amenable to genetic and experimental manipulation such as the laboratory mouse, I coupled high resolution morpho-anatomical MRI with network-based approaches on a large cohort of genetically-homogeneous wild-type mice (C57Bl6/J). To this purpose, I first developed a semi-automated pipeline enabling reliable Voxel Based Morphometry (VBM) of gray matter volumes in the mouse. To validate this approach and its ability to detect plastic changes in brain structures, I applied it to a cohort of aged mice treated with omega-3 polyunsaturated fatty acids (n3-PUFA). This study revealed that treatment with n3PUFA, but not isocaloric olive oil preserved gray matter volume of the hippocampus and frontal cortices, an effect coincident with amelioration of hippocampal-based spatial memory functions. I next employed VBM to investigate scMRI networks in inbred mice using a seed-based approach. In striking resemblance with human findings, I observed the presence of homotopic (i.e. bilateral) architecture in several scMRI cortical and subcortical networks, a finding corroborated by Independent Component Analyses. Subcortical structures also showed highly symmetric inter-hemispheric correlations, with evidence of distributed antero-posterior networks in diencephalic regions of the thalamus and hypothalamus. Hierarchical cluster analysis revealed six identifiable clusters of cortical and sub-cortical regions corresponding to previously described neuroanatomical systems. This work documents for the first time the presence of homotopic cortical and subcortical scMRI networks in the mouse brain, and is poised to pave the way to translational use of this species to investigate the elusive biological and neuroanatomical underpinnings of scMRI network development and its derangement in neuropathological states.
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Tunca, Cansu 1977. "Synaptic plasticity in the MyosinVa mutant mouse." Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/46662.
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Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2009.Includes bibliographical references (leaves 32-41).
The trafficking of essential proteins into spines is an important aspect of synaptic plasticity. MyosinVa, an actin-based motor protein, has been implicated in the synaptic delivery of AMPARs during LTP [1]. However an earlier study showed that LTP and LTD were unaffected in the MyosinVa-null dilute-lethal mice [2]. To evaluate the role of MyosinVa in synaptic plasticity, we studied different forms of LTP and LTD in the CA1 region of the hippocanmpus from MyosinVa dominant negative mutant flailer mouse using field potential recordings. Flailer mice showed no impairment of LTP or NMDAR-dependent LTD, consistent with the findings of the study on dilute-lethal. In addition, MyosinVa has been implicated in the transport of an RNA-binding protein into the spines upon mGluR activation [3]. We explored protein synthesis and mGluR-dcpendent LTD in flailer. The preliminary data we obtained show a transient impairment in mGluR.-LTD, suggesting a role for MyosinVa in protein synthesis dependent plasticity.
by Cansu Tunca.
S.M.
11
Laitinen, Päivi. "Antizyme in the regulation of mouse brain ornithine decarboxylase." Oulu : University of Oulu, 1986. http://catalog.hathitrust.org/api/volumes/oclc/16882622.html.
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Heverin, Maura. "Brain cholesterol metabolism : a study of mouse and man /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-474-0/.
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Cizeron, Mélissa. "Synaptome mapping of glutamatergic synapses across the mouse brain." Thesis, University of Edinburgh, 2017. http://hdl.handle.net/1842/28739.
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Synapses are specialised contacts between neurons. At postsynaptic terminals of glutamatergic synapses, protein complexes process and transmit the information received from the presynaptic terminal. Scaffolding proteins, among which members of the disc large homologue (DLG) family are the most abundant, assemble the molecular machinery in the postsynaptic terminal. Recently, two members of the DLG family, postsynaptic density protein 95 (PSD95) and synapse associated protein 102 (SAP102), have been shown to form different types of complexes, thus giving the synapse different signalling capabilities. However, the spatial distribution of these synaptic markers in different synapses remains elusive due to technical challenges. This thesis presents the first applications of a new method, the Genes to Cognition Synaptome Mapping pipeline (G2CSynMapp), to map individual synapses at the whole-brain level, in a quantitative and unbiased manner. This method was used to generate PSD95 and SAP102 synaptome maps – i.e. comprehensive maps of PSD95 and SAP102 positive synapses – in the mouse brain and to achieve three aims: i) characterise PSD95 and SAP102 synapse diversity, ii) measure the trajectory of PSD95 and SAP102 synapse changes during the postnatal lifespan and iii) determine whether PSD95 synaptome is reorganised by mutation. First, I have used G2CSynMapp to generate the first synaptome maps in the adult mouse brain. This reference map of PSD95 and SAP102 positive synapses revealed a highly organised distribution pattern of glutamatergic synapses between anatomical regions. Moreover, it uncovered that synapse populations are very diverse within anatomical regions and can form patches, gradients and input-specific glomeruli. Second, the trajectories of PSD95 and SAP102 synaptomes were mapped across the mouse postnatal lifespan. At birth, synapse densities are low and increase rapidly during the first month of life. During ageing, the density of SAP102 and PSD95 positive synapses decrease gradually. Interestingly, different anatomical regions show different trajectories of synapse density and parameters across the lifespan. Moreover, the packing of PSD95 and SAP102 at synapses have specific pattern of changes. Third, the PSD95 synaptome was found to be reorganised differently in two disease models, PSD93 and SAP102 knock-out mice. In humans, mutations in the genes encoding PSD93 or SAP102 have been involved in schizophrenia and mental retardation, respectively. Of particular interest, opposite changes were identified in the neocortex of the two mutant lines that are reminiscent of their inverse behavioural phenotypes.
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Copeland, Benjamin J. "Dopamine transport is altered by stress in mouse brain /." The Ohio State University, 1997. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487944660930173.
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Bittermann, Elizabeth A. "The Roles of Tubulins in the Developing Mouse Brain." University of Cincinnati / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1523630790076922.
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Kitajima, Kazuhito. "Localization of Id2 mRNA in the adult mouse brain." Kyoto University, 2006. http://hdl.handle.net/2433/143851.
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Kyoto University (京都大学)0048
新制・課程博士
博士(医学)
甲第12218号
医博第2971号
新制||医||921(附属図書館)
24054
UT51-2006-J211
京都大学大学院医学研究科脳統御医科学系専攻
(主査)教授 影山 龍一郎, 教授 塩田 浩平, 教授 瀬原 淳子
学位規則第4条第1項該当
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Fedele, Stefania. "Repetitive elements in the mouse brain: expression and regulation." Doctoral thesis, SISSA, 2012. http://hdl.handle.net/20.500.11767/4715.
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Retrotransposons are expressed in a cell type-specific manner contributing to cellular differentiation and physiological activities. In brain they are expressed as independent transcriptional units or embedded in transcripts regulating RNA splicing, dendritic localization and translation. They can also mobilize to a different genomic position changing the DNA landscape of neurons. The contribution of repetitive elements to the structure of the transcriptome of an adult neuron is still unclear. To this purpose, I have analyzed the expression and regulation of the two families of retrotransposons: SINEs (Short INterspersed Element) and LINEs (Long INterspersed Element) transposable elements. In the first part, I describe the expression of SINE.IDs, belong to a repetitive family evolutionary derived from retrotransposition of their master gene BC1.
By taking advantage of nanoCAGE, we have described the transcriptional landscape of dopaminergic neurons in the Substantia Nigra of the mouse mesencephalon, a major neuronal cell group implicated in Parkinson’s Disease (PD). Together with a definition of the repertory of repetitive elements expressed in these adult neurons, I have identified a large number of different SINE.IDs that are independently expressed in the wild-type mouse brain and in the BC1 KO mice. In particular, I have shown that single SINE.IDs are differentially expressed in mouse brain regions as independent transcriptional units and are regulated during neuronal cell differentiation in a dopaminergic cell line model. The precise temporal and spatial expression of ncRNAs appears to be exceptionally important for mediating CNS form and function. In this case, our data support the hypothesis that repetitive sequences, such as SINE.IDs, are regulated and selectively targeted to specific cellular domains in subsets of neurons of the rodent nervous system. In the second part, I study potential effects of dietary regimens on the genomic landscape of the brain. Nutritional and metabolic factors are associated with onset and progression of neurodegenerative disorders. In particular, B vitamin deprivation and hyperhomocysteinemia is associated with Alzheimer’s disease, by inhibiting DNA methylation of related genes, such as PSEN1. Supporting a strong link between dietary and DNA methylation status, I have hypothesized that retrotranspositional events may be regulated by the B vitamin content of food intake. To this propose, a TaqMan qPCR assay has been developed in mouse for studying LINE1 copy number variation of different repetitive element families. By taking advantage of this new tool, I have unveiled that brain cells present an higher LINE1 content than non-brain tissues. Furthermore, I have accumulated preliminary data suggesting copy number variations triggered by dietary regimens.
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Rikhye, Rajeev V. (Rajeev Vijay). "The mechanisms of reliable coding in mouse visual cortex." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/107559.
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Thesis: Ph. D. in Neuroscience, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2016.Cataloged from PDF version of thesis. Page 262 blank.
Includes bibliographical references.
As we interact with the environment, our senses are constantly bombarded with information. Neurons in the visual cortex have to transform these complex inputs into robust and parsimonious neural codes that effectively guide behavior. The ability of neurons to efficiently convey information is, however, limited by intrinsic and shared variability. Despite this limitation, neurons in primary visual cortex (V1) are able to respond with high fidelity to relevant stimuli. My thesis proposes that high fidelity encoding can be achieved by dynamically increasing trial-to-trial response reliability. In particular, in this thesis, I use the mouse primary visual cortex (V1) as a model to understand how reliable coding arises, and why it is important for visual perception. Using a combination of novel experimental and computational techniques, my thesis identifies three main factors that can modulate intrinsic variability. My first goal was to understand the extrinsic, stimulus-dependent, factors responsible for reliably coding (Chapter 3). Natural scenes contain unique statistical properties that could be leveraged by the visual cortex for efficient coding. Thus, the first aim is to elucidate how image statistics modulate reliable coding in V1. To this end, I developed a novel noise masking procedure that allowed us to specifically perturb the spectral content of natural movies without altering the edges. Using high-speed twophoton calcium imaging in mice, I discovered that movies with stronger spatial correlations are more reliably processed by V1 neurons than movies lacking these correlations. In particular, perturbing spatial correlations in the movie dynamically altered the structure of interneuronal correlations. Movies with more naturalistic correlations typically recruited large neuronal ensembles that were weakly noise correlated. Using computational modeling, I discovered that these ensembles were able reduce shared noise through divisive normalization. Together, these findings demonstrate that natural scene statistics dynamically recruit neuronal ensembles to ensure reliable coding. Microcircuits of inhibitory interneurons lie at the heart of all cortical computations. It has been proposed that these interneurons are responsible for reliable spiking by controlling the temporal window over which synaptic inputs are integrated. However, no study has yet conclusively investigated the role of different interneuron subtypes. Thus, my second goal was to establish how natural scenes are reliably encoded by dissecting the inhibitory mechanisms underlying reliable coding (Chapter 4). Specifically, I investigated the role of somatostatin-expressing dendrite targeting interneurons (SST) and parvalbumin-expressing soma targeting interneurons (PV), which are known to provide distinct forms of inhibition onto pyramidal neurons. Using a novel combination of dual-color calcium imaging and optogenetic manipulation, I have discovered that the SST->PV inhibitory circuit plays a crucial role in modulating pyramidal cell reliability. In particular, by transiently suppressing PV neurons, SST neurons are able to route inhibition rapidly from the soma to the dendrites. Strong dendritic inhibition allows noisy inputs to be filtered out by the dendrites, while weaker somatic inhibition allows these inputs to be integrated to produce reliable spikes. In agreement with these results, I found that selectively deleting MeCP2 from these interneurons resulted in unreliable visual processing and other circuit-specific deficits, which are commonly observed in Rett Syndrome (Chapter 5). These results underscore the importance of intact inhibitory microcircuits in reliable processing. Finally, my goal was to determine why reliable coding is necessary for visual processing (Chapter 6). To this end, I trained head-fixed mice to perform a natural movie discrimination task. Mice were able to learn how to discriminate between two movies after a short training period. By perturbing the amplitude spectrum of these movies, I discovered that mice used structural information in the phase spectrum to discriminate between the different movies. This suggests that mice also use similar strategies as higher mammals for scene recognition. Inspired by this result, we trained mice on a harder target categorization task, where mice had to identify the movies from an ensemble that were more similar to the target movie to gain a water reward. We developed this movie ensemble by blending together the phase spectrum of a target and non-target movie at different fractions. Optically activating SST neurons in V1 improved the ability of mice to correctly identify "target-like" movies. This increase in behavioral performance correlated well with an increase in V1 coding reliability. Thus, reliable codes are a prerequisite for accurate visual perception. Taken together, this work bridges the gap between cells, circuits and behavior, and provides mechanistic insight into how complex visual stimuli are encoded with high fidelity in the visual cortex.
by Rajeev V. Rikhye.
Ph. D. in Neuroscience
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Schmidt, Carolin. "Identification and functional associations of CD9 in the mouse brain /." [S.l.] : [s.n.], 1993. http://e-collection.ethbib.ethz.ch/show?type=diss&nr=10459.
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Zhu, Shun-Wei. "Brain neurotrophin levels and mouse behavior : relationship to environmental influences /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-843-6/.
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Stevenson, Philip G. "The immune response to viral antigens in the mouse brain." Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364023.
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Gerkau, Niklas [Verfasser]. "Intracellular Sodium and Energy Metabolism in Mouse Brain / Niklas Gerkau." Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2018. http://d-nb.info/1172500290/34.
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Bagdatlioglu, Emine. "Investigating the brain in mouse models of Duchenne muscular dystrophy." Thesis, University of Newcastle upon Tyne, 2017. http://hdl.handle.net/10443/3931.
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Duchenne muscular dystrophy (DMD) is an X-linked recessive muscle wasting disease caused by mutations in the DMD gene, which encodes the large cytoskeletal protein dystrophin. Alongside severe muscle pathology, one-third of DMD patients exhibit cognitive problems ranging from reduced verbal intelligence to severe autism. There is conclusive evidence that the muscle pathology exhibited by DMD patients is progressive, yet it remains unknown whether the cognitive impairments in DMD are also progressive. Previous studies have highlighted a cognitive impairment in the mdx mouse model of DMD, but no studies have investigated if this cognitive impairment worsens with age. We assessed the consequences of dystrophin deficiency on brain morphology and cognitive function in two dystrophin-deficient mouse models (mdx and Cmah-/-mdx mice). The overall project aim was to identify outcome measures to monitor central nervous system (CNS) pathology non-invasively in DMD mice. Magnetic resonance imaging (MRI) identified a total brain volume increase in DMD mice, alongside morphological changes in brain ventricles. Behavioural testing revealed a deficit in hippocampal spatial learning and memory, particularly long-term memory, in mdx mice, which appears to progressively worsen with age. Immunoblotting identified a progressive reduction of aquaporin-4 (AQP4) expression, the major water channel of the CNS, in DMD mice. Moreover, contrast enhancing MRI and Evans blue extravasation demonstrated a progressive impairment in blood-brain barrier (BBB) integrity in mdx mice. Proteomic profiling of the mdx cerebellum identified changes in expression of mitochondrial subunit complexes, suggestive of changes in mitochondrial function. Additionally, elevated levels of inflammatory markers were identified and confirmed in the mdx cerebellum. Our studies suggest that dystrophin deficiency causes a progressive cognitive impairment in mdx mice. We also present evidence showing that changes in osmotic equilibrium may be involved in the pathogenesis of DMD, with reductions in AQP4 expression and BBB disruptions. We speculate that some of the changes in the mdx cerebellar proteome, in comparison to wild type mice, iii serve as compensatory mechanisms whilst others may contribute directly to cognitive dysfunction in DMD. These results support a role for dystrophin in normal brain morphology and cognitive function.
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Capela, Maria Alexandra Nunes. "Neural stem cells in the embryonic and adult mouse brain." Doctoral thesis, Porto : Edição do Autor, 2002. http://hdl.handle.net/10216/64573.
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Mauthe, Constanze [Verfasser]. "Afferents to the presubiculum in the mouse brain / Constanze Mauthe." Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2016. http://d-nb.info/1112133046/34.
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Capela, Maria Alexandra Nunes. "Neural stem cells in the embryonic and adult mouse brain." Tese, Porto : Edição do Autor, 2002. http://catalogo.up.pt/F?func=find-b&local_base=UPB01&find_code=SYS&request=000090403.
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SENZACQUA, MARTINA. "Action of ciliary neurotrophic factor on mouse brain feeding centers." Doctoral thesis, Università Politecnica delle Marche, 2018. http://hdl.handle.net/11566/253101.
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Il fattore neurotrofico ciliare (CNTF) induce sazietà e aumento della spesa energetica nell’uomo e nei roditori, agendo a livello cellulare con un meccanismo simile a quello della leptina, attraverso la via di trasduzione Jak-STAT3. Studi recenti hanno evidenziato che nell’ipotalamo tuberale di topo il CNTF è espresso da cellule gliali e il suo meccanismo d’azione è potenziato in modelli sperimentali di obesità. Mediante studi di immunoistochimica, abbiamo dimostrato che la somministrazione di CNTF induce l’attivazione di STAT1 e STAT5 nell’ipotalamo tuberale, in particolare nelle cellule ependimali del terzo ventricolo, nei β-taniciti e cellule gliali dell’eminenza mediana. In questa sede, inoltre, il CNTF attiva il c-Fos, marker di attivazione cellulare. Abbiamo poi verificato l’ipotesi che il CNTF potesse agire anche a livello dei centri truncali, altra sede importante per il controllo del comportamento alimentare. Il CNTF nell’area postrema di topo, come nell’eminenza mediana, attiva STAT3, STAT1 e STAT5. Studi di co-localizzazione hanno evidenziato che gran parte di queste cellule gliali responsive al CNTF esprimono tipici marker di immaturità, nestina e vimentina. Dopo 120 minuti dal trattamento con CNTF abbiamo osservato una forte attivazione di c-Fos nei neuroni del nucleo del tratto solitario e una debole attivazione dello stesso marker in alcuni neuroni colinergici del nucleo motore dorsale del vago. Il doppio trattamento con CNTF (120 minuti, per indurre espressione di c-Fos) e con leptina (25 minuti, per indurre fosforilazione di STAT3) ha permesso di dimostrare la co-localizzazione dei due marker in una piccola popolazione di neuroni nella porzione caudale del nucleo del tratto solitario. Inoltre, nell’area postrema, si evidenzia una notevole discrepanza tra le numerose cellule responsive al CNTF e quelle che lo producono, le quali sono poche cellule gliali situate nel funiculus separans e nelle meningi. Questo disaccoppiamento tra espressione del CNTF e del suo recettore è stato confermato da studi di RT-qPCR, sia a livello dell’area postrema che dell’ipotalamo. Il CNTF rappresenta quindi un nuovo fattore di sazietà coinvolto nella regolazione del bilancio energetico che esercita un’azione parallela e ridondante a livello dell’ipotalamo e del tronco encefalico.The ciliary neurotrophic factor (CNTF) induces satiety and increase of energy expenditure in rodents and human through a leptin-like activation of the Jak-STAT3 signaling pathway. Recent studies demonstrated that CNTF is constitutively produced by hypothalamic glial cells and that its expression is up-regulated in obese mice. By immunohistochemistry studies, we demonstrated that after systemic treatment, rat recombinant CNTF induced activation of STAT1 and STAT5 in the tuberal hypothalamus of mice, in particular in ependymal cells bordering the third ventricle floor and lateral recesses, and in median eminence β-tanycytes and glial cells. Moreover, STAT activation was accompanied by c-Fos expression in β-tanycytes and median eminence cells of CNTF-treated mice. We tested the hypothesis that CNTF also affects the brainstem centers involved in energy homeostasis. In the area postrema of mice, as well as in the median eminence, CNTF activates STAT3, STAT1 and STAT5. Co-localization studies showed that a significant proportion of CNTF-responsive glial cells were also positive for immaturity and plasticity markers nestin and vimentin. After 120 min from the treatment, we observed a strong c-Fos expression in several neurons of the rostral and caudal solitary tract nucleus (NTS) and a weak c-Fos immunostaining in some cholinergic neurons of the dorsal motor nucleus of the vagus. Treatment with CNTF (120 min, to induce c-Fos expression) and leptin (25 min, to induce STAT3 phosphorylation) demonstrated the co-localization of the two markers in a small percentage of neurons in the caudal NTS portion. In contrast to the high responsiveness to CNTF, in the area postrema CNTF immunoreactivity is weak and sparse, and mainly detected in glial cells of the funiculus separans and meninges. RT-qPCR in micropunched area postrema and hypothalamus mouse tissues highlights the big discrepancy between CNTF and CNTF receptor expression in both the two brain regions examined. In conclusion, CNTF represents a new satiety factor involved in the pathophysiological regulation of the energy balance that exerts a parallel and redundant action in hypothalamic and brainstem feeding centers.
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Muhammad, Rahmat. "The mouse visually evoked potential : neural correlates and functional applications." Thesis, Massachusetts Institute of Technology, 2009. http://hdl.handle.net/1721.1/46388.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2009.This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections.
"February 2009."
Includes bibliographical references.
The visually evoked potential (VEP) is a local field potential (LFP) evoked in visual cortex in response to visual stimuli. Unlike extracellular single unit recordings, which allow us to probe the function of single spiking cells acutely, the chronic VEP technique gives us insight into ensemble synaptic activity. However, while action potentials are easily interpreted as the output of the recorded neuron, LFPs are difficult to interpret because they may reflect the sum of activity occurring at or beyond the site of recording. The goal of this study was to use the current source density (CSD) method to derive information about synaptic activity occurring at the site of recording and to determine how this activity relates to the concurrent LFP. The mouse has recently become a widely-used experimental model for studying the mechanisms of plasticity and there has been an increase in the use of VEP recordings to study experience-dependent changes in mouse primary visual cortex (V1). These studies typically focus on changes occurring in the layer 4 VEP after a variable period of visual deprivation. Layer 4 of mouse V1 receives heavy direct input from the lateral geniculate nucleus. This initial input is followed by strict hierarchical connectivity from cortical layer 4 to superficial layers 2/3 and from 2/3 to deep layers 5/6. Using a method for silencing cortical activity without affecting geniculate input activity in conjunction with CSD analyses, we found that the laminar flow of activity in mouse V1 in response to various grating stimuli was consistent with the anatomical connectivity going from layer 4 ?? 2/3 ?? 5/6. To determine if the layer 4 VEP is indeed reflecting synaptic activity occurring in layer 4, we applied the CSD method to field potentials recorded from mouse V1. Our results indicate that changes in the layer 4 VEP strongly and significantly covaries with changes in layer 4 current sink activity suggesting that the layer 4 VEP is indeed reflecting local layer 4 synaptic activity.
(cont.) This layer 4 activity is likely due to direct geniculate input since it persisted after intracortical activity was blocked. If the layer 4 VEP reflects synaptic activity due to direct geniculo-cortical input and if this input is carrying information about the visual world then we would expect the VEP to change as the parameters of the stimuli vary. Indeed the binocular-driven VEP broadened in shape as we increased the spatial frequency (SF) of grating stimuli. Using CSD analyses, we were able to trace the transformations of the layer 4 VEP waveform to changes happening in layer 4 current sinks and layer 4 current sinks were in turn affected by events in deep layers. Specifically, increasing SF of the grating stimuli led to a reduction of current sink activity in deep layers and this unmasked prolonged current sink activity in layer 4. This prolonged layer 4 current sink activity persisted after cortical silencing suggesting that it is likely due to late-onset direct geniculate input. We suggest that late-onset activity from the ipsilateral-eye may be unmasked with increasing SF. VEPs have been used extensively in the clinical and laboratory setting to determine visual acuity in humans as well as anaesthetized animals. If the layer 4 VEP is to be a useful measure of visual function in awake head-fixed mice, VEP-assessed visual acuity and contrast sensitivity should be consistent with behaviorally-assessed measures. We found that VEP-assessed visual acuity agreed with previous behaviorally-assessed acuity; however, VEP-assessed contrast-sensitivity values were slightly higher. One of the reasons why inbred laboratory mice are becoming increasingly useful in Neuroscience is because individual mice are genetically identical and any behavioral variability should be experience-driven. While this is true for mice within a given strain, it is not true between strains since strains are genetically different. Therefore, it is crucial to understand how strain differences in genes affects neural activity before comparing results from different strains.
(cont.) To this end, we compared the VEP response of two commonly used laboratory mouse strains: C57BL/6 and 129/Sv and found important differences in the VEP waveform which may translate into differences in visual function. Specifically, our data suggest that 129/Sv mice may have better acuity than C57BL/6 mice. The advent of molecular engineering tools is another reason why the mouse has become the preferred model system for studying the cellular and molecular mechanisms underlying behavioral and physiological phenomena. Genetically modified mice are routinely screened for behavioral deficits using tasks such as the Morris watermaze -- test for spatial navigation which assumes that the mice have functional vision. In order to remove the experimental confound of vision, the layer 4 VEP can be used to assay the visual function of mice prior to behavioral experimentation. Using the VEP technique, we determined the visual function of Shank1-/- mice to be normal in response to low SF gratings but impaired in response to high SF gratings. Shank1-/- mice were not impaired in the eight-arm radial maze task - another test of spatial navigation suggesting that low SF vision may be sufficient for performing this task. Taken together, this study demonstrates that the VEP is an interpretable and useful recording technique which can be combined with CSD analysis to determine the laminar activity patterns which underlie visual function in the awake mouse.
by Rahmat Muhammad.
Ph.D.
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Schenk, Sarah E. "Acute and recurrent hypoglycemia modulates brain glycogen metabolism in the mouse." Muncie, Ind. : Ball State University, 2009. http://cardinalscholar.bsu.edu/618.
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Ganea, Karin. "Identification and characterisation of novel antidepressant-responsive genes in mouse brain." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-99940.
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Collins, Mark Oliver. "Analysis of the molecular components and phosphorylation of mouse brain proteomes." Thesis, University of Edinburgh, 2006. http://hdl.handle.net/1842/24472.
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We have developed upon existing immobilised metal-affinity chromatography (IMAC) techniques for capturing phosphopeptides, to selectively purify phosphoproteins from complex mixtures. Using this novel approach, combining both protein and peptide IMAC and MS data acquisition strategies, a comprehensive map of the mouse forebrain cytosolic phosphoproteome was achieved. This new approach was applied to purified mouse forebrain synaptosomes and resulted in the first large-scale map of the mouse synapse phosphoproteome. We have detected over 650 phosphorylation events, corresponding to 331 unique phosphorylation sites on synaptic proteins. 92% of these phosphorylation sites are novel, indicating a previously underestimated complexity in synaptic signalling. Bioinformatic and in vitro phosphorylation assays of peptide arrays suggest a small number of kinases phosphorylate many proteins and each substrate is phosphorylated by many kinases. In recent years, mass spectrometry (MS) based analysis of the postsynaptic density (PSD) and receptor complexes, have established for the first time a detailed list of its molecular components. In order to provide a coherent map of the molecular components of the synapse proteome, a bioinformatic approach was used to combine six PSD and three postsynaptic receptor complex datasets into a single database of synaptic proteins. This process of data integration allowed comparisons of analytical approaches used and revealed the most effective biochemical and MS-based methodologies. This data was used as a framework on which multiple data sources were integrated and allowed the derivation of proteome-wide molecular network maps at the level of gene regulation, protein interaction and protein phosphorylation. These maps were merged with functional or phenotype data from individual molecule studies to derive new models of synapse function.
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Boulanger, Jenna. "Stereological Analysis of Oligodendrocyte Progenitor Cells In the Adult Mouse Brain." Thesis, Université d'Ottawa / University of Ottawa, 2017. http://hdl.handle.net/10393/36352.
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The main goal of this study was to further explore the hypothesis that experience-dependent neural network activity and neurotransmission can modulate adult OPC proliferation and differentiation. More specifically, we used stereology to establish whether extensive reference memory training and system-wide administration of GABAergic agonists and antagonists could influence the proliferation and differentiation of adult OPCs, as well as the prevalence of OPC-neuron pairs. Analysis of the effects of reference memory training on OPC proliferation and differentiation corresponds to experiment 2, analysis of the effects of GABAergic agents on OPC proliferation and differentiation corresponds to experiment 3, and analysis of the effects of both reference memory training and GABAergic agents on OPC-neuron pairs, as well as an histological analysis of these closely apposed cells, corresponds to experiment 4.
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Chen, Zhiguo. "Excitotoxic neurodegeneration in mouse brain : roles of immune cells and cytokines /." Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-873-4/.
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羅慧詩 and Wai-sze Law. "Conditional knockout of neural cell adhesion molecule L1 in mouse brain." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B42575266.
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Smith, Maria Civita. "MAPPING ASTROCYTE DEVELOPMENT IN THE DORSAL CORTEX OF THE MOUSE BRAIN." Case Western Reserve University School of Graduate Studies / OhioLINK, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=case1373039738.
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Bidinotto, Paige A. "Neuroanatomical and Cellular Localization of Luteinizing Hormone in the Mouse Brain." Kent State University Honors College / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ksuhonors1494786204688846.
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Nguyen, Peter. "CANNABINOID RECEPTORS IN THE 3D RECONSTRUCTED MOUSE BRAIN: FUNCTION AND REGULATION." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2274.
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CB1 receptors (CB1R) mediate the psychoactive and therapeutic effects of cannabinoids including ∆9-tetrahydrocannabinol (THC), the main psychoactive constituent in marijuana. However, therapeutic use is limited by side effects and tolerance and dependence with chronic administration. Tolerance to cannabinoid-mediated effects is associated with CB1R adaptations, including desensitization (receptor-G-protein uncoupling) and downregulation (receptor degradation). The objectives of this thesis are to investigate the regional-specificity in CB1R function and regulation. Previous studies have investigated CB1Rs in a subset of regions involved in cannabinoid effects, but an inclusive regional comparison of the relative efficacies of different classes of cannabinoids to activate G-proteins has not been conducted. A novel unbiased whole-brain analysis was developed based on Statistical Parametric Mapping (SPM) for 3D-reconstructed mouse brain images derived from agonist-stimulated [35S]GTPgS autoradiography, which has not been described before. SPM demonstrated regional differences in the relative efficacies of cannabinoid agonists methanandamide (M-AEA), CP55,940 (CP), and WIN55,212-2 (WIN) in mouse brains. To assess potential contribution of novel sites, CB1R knockout (KO) mice were used. SPM analysis revealed that WIN, but not CP or M-AEA, stimulated [35S]GTPgS binding in regions that partially overlapped with the expression of CB1Rs. We then examined the role of the regulatory protein Beta-arrestin-2 (βarr2) in CB1R adaptations to chronic THC treatment. Deletion of βarr2 reduced CB1R desensitization/downregulation in the cerebellum, caudal periaqueductal gray (PAG), and spinal cord. However in hippocampus, amygdala and rostral PAG, similar desensitization was present in both genotypes. Interestingly, enhanced desensitization was found in the hypothalamus and cortex in βarr2 KO animals. Intra-regional differences in the magnitude of desensitization were noted in the caudal hippocampus, where βarr2 KO animals exhibited greater desensitization compared to WT. Regional differences in βarr2-mediated CB1R adaptation were associated with differential effects on tolerance, where THC-mediated antinociception, but not catalepsy or hypothermia, was attenuated in βarr2 KO mice. Overall, studies using SPM revealed intra- and inter-regional specificity in the function and regulation of CB1Rs and underscores an advantage of using a whole-brain unbiased approach. Understanding the regulation of CB1R signaling within different anatomical contexts represents an important fundamental prerequisite in the therapeutic exploitation of the cannabinoid system.
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Law, Wai-sze. "Conditional knockout of neural cell adhesion molecule L1 in mouse brain." Click to view the E-thesis via HKUTO, 2000. http://sunzi.lib.hku.hk/hkuto/record/B42575266.
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Garin, Clément. "Characterization of Mouse Lemur Brain by Anatomical, Functional and Glutamate MRI." Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS174/document.
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Le microcèbe murin (Microcebus murinus) est un primate attirant l’attention de la recherche neuroscientifique. Son anatomie cérébrale est encore mal décrite et ses réseaux cérébraux n'ont jamais été étudiés. Le premier objectif de cette thèse était de développer de nouveaux outils menant à la création d’un atlas numérique 3D du cerveau du microcèbe. Cet atlas est un outil fondamental car pouvant être utilisé pour extraire automatiquement des biomarqueurs cérébraux de diverses neuropathologies. Par la suite, nous avons mis en place des protocoles IRM et informatiques pour analyser la connectivité neuronale du microcèbe murin. Nous avons évalué pour la première fois les réseaux cérébraux de cet animal et révélé que son cerveau est organisé en régions fonctionnelles intégrées dans des réseaux fonctionnels à plus grande échelle. Ces réseaux ont été classés et comparés à des réseaux similaires chez l'homme. Cette comparaison multi-espèces a mis en évidence des règles d'organisation communes mais aussi des divergences. L'imagerie du glutamate par transfert de saturation et par échange chimique (gluCEST) est une méthode permettant de créer des cartes 3D de la distribution du glutamate. Dans une troisième étude, nous avons comparé l’activité neuronale locale, la connectivité fonctionnelle et le contraste gluCEST dans diverses régions du cerveau. Nous avons ainsi mis en évidence différentes associations entre ces trois biomarqueurs. Enfin, l’impact du vieillissement sur la connectivité fonctionnelle, l’activité neuronale locale et le contraste gluCEST a été évalué en comparant deux cohortes de microcèbes murinsThe mouse lemur (Microcebus murinus) is a primate that has attracted attention within neuroscience research. Its cerebral anatomy is still poorly described and its cerebral networks have never been investigated. The first objective of this study was to develop new tools to create a 3D digital atlas of the brain of this model and to use this atlas to automatically follow-up brain characteristics in cohorts of animals. We then implemented protocols to analyze connectivity in mouse lemurs so we could evaluate for the first time the cerebral networks in this species. We revealed that the mouse lemur brain is organised in local functional regions integrated within large scale functional networks. These latter networks were classified and compared to large scale networks in humans. This multispecies comparison highlighted common organization rules but also discrepancies. Additionally, Chemical Exchange Saturation Transfer imaging of glutamate (gluCEST) is a method that allows the creation of 3D maps weighted by the glutamate distribution. In a third study, we compared local neuronal activity, functional connectivity and gluCEST contrast in various brain regions. We highlighted various associations between these three biomarkers. Lastly, the impact of aging on local neuronal activity, functional connectivity and gluCEST has been analyzed by comparing two cohorts of lemurs
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Liska, Adam. "Brain functional connectivity and its aberrations in mouse models of autism." Doctoral thesis, Università degli studi di Trento, 2017. https://hdl.handle.net/11572/369283.
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Functional Magnetic Resonance Imaging (fMRI) has consistently highlighted aberrant functional connectivity across brain regions of autism spectrum disorder (ASD) patients. However, the manifestation and neural substrates of these alterations are highly heterogeneous and often conflicting. Moreover, their neurobiological under- pinnings and etiopathological significance remain largely unknown. A deeper understanding of the complex pathophysiological cascade leading to impaired connectivity in ASD can greatly benefit from the use of model organisms where individual pathophysiological or phenotypic components of ASD can be recreated and investigated via approaches that are either off limits or confounded by clinical heterogeneity.
In this work, we first describe the intrinsic organization of the mouse brain at the macroscale as seen through resting-state fMRI (rsfMRI). The analysis of a large rsfMRI dataset revealed the presence of six distinct functional modules related to known brainwide functional partitions, including a homologue of the human default-mode network (DMN). Consistent with human studies, interconnected functional hubs were identified in several sub-regions of the DMN, in the thalamus, and in small foci within integrative cortical structures such as the insular and temporal association cortices.
We then study the effects of mutations in contactin associated protein-like 2 (Cntnap2), a neurexin-related cell-adhesion protein, on functional connectivity. Homozygous mutations in this gene are strongly linked to autism and epilepsy in humans, and using rsfMRI, we showed that homozygous mice lacking Cntnap2 exhibit aberrant functional connectivity in prefrontal and midline functional hubs, an effect that was associated with reduced social investigation, a core “autism trait†in mice. Notably, viral tracing revealed reduced frequency of prefrontal-projecting neural clusters in the cingulate cortex of Cntnap2−/− mutants, suggesting a possible contribution of defective mesoscale axonal wiring to the observed functional impairments. Macroscale cortico-cortical white-matter organization appeared to be otherwise preserved in these animals. These findings revealed a key contribution of ASD-associated gene CNTNAP2 in modulating macroscale functional connectivity, and suggest that homozygous loss-of-function mutations in this gene may predispose to neurodevelopmental disorders and autism through a selective dysregulation of connectivity in integrative prefrontal areas.
Finally, we discuss the role mouse models could play in generating and testing mechanistic hypotheses about the elusive origin and significance of connectional aberrations observed in autism and recent progress towards this goal.
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Liska, Adam. "Brain functional connectivity and its aberrations in mouse models of autism." Doctoral thesis, University of Trento, 2017. http://eprints-phd.biblio.unitn.it/2722/1/phd_thesis_adam_liska.pdf.
Full textAbstract:
Functional Magnetic Resonance Imaging (fMRI) has consistently highlighted aberrant functional connectivity across brain regions of autism spectrum disorder (ASD) patients. However, the manifestation and neural substrates of these alterations are highly heterogeneous and often conflicting. Moreover, their neurobiological under- pinnings and etiopathological significance remain largely unknown. A deeper understanding of the complex pathophysiological cascade leading to impaired connectivity in ASD can greatly benefit from the use of model organisms where individual pathophysiological or phenotypic components of ASD can be recreated and investigated via approaches that are either off limits or confounded by clinical heterogeneity.
In this work, we first describe the intrinsic organization of the mouse brain at the macroscale as seen through resting-state fMRI (rsfMRI). The analysis of a large rsfMRI dataset revealed the presence of six distinct functional modules related to known brainwide functional partitions, including a homologue of the human default-mode network (DMN). Consistent with human studies, interconnected functional hubs were identified in several sub-regions of the DMN, in the thalamus, and in small foci within integrative cortical structures such as the insular and temporal association cortices.
We then study the effects of mutations in contactin associated protein-like 2 (Cntnap2), a neurexin-related cell-adhesion protein, on functional connectivity. Homozygous mutations in this gene are strongly linked to autism and epilepsy in humans, and using rsfMRI, we showed that homozygous mice lacking Cntnap2 exhibit aberrant functional connectivity in prefrontal and midline functional hubs, an effect that was associated with reduced social investigation, a core “autism trait” in mice. Notably, viral tracing revealed reduced frequency of prefrontal-projecting neural clusters in the cingulate cortex of Cntnap2−/− mutants, suggesting a possible contribution of defective mesoscale axonal wiring to the observed functional impairments. Macroscale cortico-cortical white-matter organization appeared to be otherwise preserved in these animals. These findings revealed a key contribution of ASD-associated gene CNTNAP2 in modulating macroscale functional connectivity, and suggest that homozygous loss-of-function mutations in this gene may predispose to neurodevelopmental disorders and autism through a selective dysregulation of connectivity in integrative prefrontal areas.
Finally, we discuss the role mouse models could play in generating and testing mechanistic hypotheses about the elusive origin and significance of connectional aberrations observed in autism and recent progress towards this goal.
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Awikunprasert, Panatsada. "The use of statistical parameter mapping for longitudinal PET/CT studies of mouse brain metabolism." Thesis, University of Aberdeen, 2010. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=163140.
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In this work, we aimed to assess the possibility of applying the SPM method to a smallanimal PET data set including the use of the SPM registration option and the investigation of its applications in translational studies. We also evaluated and determined which image registration technique is best suited for aligning mice brain PET/CT images. Methods: The data were acquired from a cohort of C57BL/6 wild-type mice which underwent PET/CT scanning, producing the matched FDG-PET and CT brain images. Three different registration techniques to align mouse brain PET images were investigated: 1) PET/PET template 2) CT/CT template and 3) the segmented mask brain registration (described below). The automatic registration package within SPM was used to register the mice brain images. Optimal parameter settings for registering mice brain images were examined. Multiple measures of accuracy including: visual inspection, volume overlap, distance error and mutual information values were used to evaluate the image registration techniques. Results: In comparison between the PET-PET and CT-CT methods, there were no statistically significant in the means of the volume overlap measures. However, the mean distance error from the CT-CT method was significantly lower than for the PET/PET method. The qualitative visual inspection results showed that there were three registered images from the PET-PET method, and two from the CT-CT method were misalignment could be detected whereas there was no image misalignment detected from the mask-mask technique. Conclusion: The use of the segmented (mask) brain registration method produced the most successful results. A major benefit of including a mask brain in the registration is that it excludes the non-brain regions which contain unwanted signal (i.e. bright intensity of eyes), ensuring that the registration procedure used specifically the brain area for registering, avoiding the other bright areas of non-brain structures.
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Greene, Matthew (Matthew Jason). "A connectomic analysis of the directional selectivity circuit in the mouse retina." Thesis, Massachusetts Institute of Technology, 2014. http://hdl.handle.net/1721.1/106432.
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Thesis: Ph. D., Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, June 2016.Cataloged from PDF version of thesis.
Includes bibliographical references (pages 51-56).
This thesis addresses the question of how direction selectivity (DS) arises in the mouse retina. DS has long been observed in retinal ganglion cells, and more recently confirmed in the starburst amacrine cell. Upstream retinal bipolar cells, however, have been shown to lac, indicating that the mechanism that gives rise to DS lies in the inner plexiform layer, where the axons of bipolar cells costratify with amacrine and ganglion cells. We reconstructed a region of the IPL and identified cell types within it, and have discovered a mechanism which may explain the origin of DS activity in the mammalian retina, which relies on what we call "space-time wiring specificity." It has been suggested that a DS signal can arise from non-DS excitatory inputs if at least one among spatially segregated inputs transmits its signal with some delay, which we extend to consider also a difference in the degree to which the signal is sustained. Previously, it has been supposed that this delay occurs within the starburst amacrine cells' dendrites. We hypothesized an alternative, presynaptic mechanism. We observed that different bipolar cell types, which are believed to express different degrees of sustained activity, contact different regions of the starburst amacrine cell dendrite, giving rise to a space-time wiring specifity that should produce a DS signal. We additionally provide a model that predicts the strength of DS as a function of the spatial segregation of inputs and the temporal delay.
by Matthew Greene.
Ph. D.
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Schecter, Rachel W. "Structural mechanisms of experience-dependent synaptic plasticity in the mouse visual cortex." Thesis, Massachusetts Institute of Technology, 2016. http://hdl.handle.net/1721.1/106441.
Full textAbstract:
Thesis: Ph. D. in Neuroscience, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2016.Vita. Cataloged from PDF version of thesis.
Includes bibliographical references (pages 151-171).
Changes in the sensory experience of an animal shapes behavior through synaptic plasticity. Modification in the strength of synaptic drive can result from adjustments in the strength of existing synapses, creation of new synapses, or removal of existing ones and involves presynaptic, postsynaptic, and extra-synaptic mechanisms. Ocular dominance (OD) plasticity following brief periods of monocular deprivation (MD) is a classic example of experience-dependent change, which leads to a rapid weakening of cortical responsiveness to the deprived eye and a strengthening of responsiveness to the non-deprived eye. Though there is clear anatomical reorganization following long periods of lid suture, only recently has brief periods (3 days) of MD has been shown to drive structural plasticity of thalamic input to binocular visual cortex. The exact molecular and synaptic mechanisms responsible for rapid OD shifts remain unclear. In my thesis work, I address the requirement of proper microglial functioning via the fractalkine receptor (CX3CR1) in OD plasticity following 3 days of MD. I first identify increased lysosomal content in microglia within layer 4 (L4) of binocular visual cortex following MD, which suggests microglia participate in this structural rearrangement. As it is currently believed that a major axis of communication between neurons and microglia occurs via fractalkine and its specific receptor CX3CR1, I investigated OD plasticity within the CX3CR1 KO mouse. My experiments reveal increased lysosomal content, structural plasticity of thalamocortical synapses, and OD shifts measured with visually evoked potentials (VEPs) all occur normally in this mutant mouse as a result of 3 days of MD with only subtle differences when compared to WT mice. I conclude that, while microglia may have a role in the anatomical and functional experience-dependent cortical plasticity driven by brief lid suture, it does not require CX3CR1.
by Rachel W. Schecter.
Ph. D. in Neuroscience
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Persson, Ann-Sophie. "The megencephaly mouse - from gene to neuronal proliferation /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-601-8/.
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Diez, Margarita. "Neuropeptide expression in mouse disease models /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-514-x/.
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Khibnik, Lena A. "Mechanisms of ocular dominance plasticity in the juvenile and adult mouse visual cortex." Thesis, Massachusetts Institute of Technology, 2011. http://hdl.handle.net/1721.1/65287.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2011.Cataloged from PDF version of thesis. Vita.
Includes bibliographical references (p. 171-185).
Ocular dominance (OD) plasticity is a classic example of bidirectional experience-dependent plasticity in the primary visual cortex. This form of plasticity is most robust during early postnatal development (termed the "critical period"), when monocular deprivation (MD) leads to a rapid weakening of responses evoked through the deprived eye followed by a delayed strengthening of non-deprived eye inputs. It has been proposed that these bidirectional changes occur as a three-stage process: first, degradation of patterned visual input weakens deprived-eye responses via homosynaptic long-term depression (LTD); this is accompanied by a shift in the plasticity modification threshold (0m) that determines the direction of synaptic plasticity, such that synaptic strengthening is favored over synaptic weakening; finally, weak open-eye responses are strengthened via the mechanisms of homosynaptic long-term potentiation (LTP). Despite the growing evidence supporting this model of experience-dependent synaptic modification, the exact molecular and synaptic mechanisms that are responsible for these processes remain controversial. In my thesis work, I address three questions. First, I attempt to parse the relative contribution of excitatory and inhibitory processes to expression of the OD shift in order to understand how deprived-eye depression is expressed in the cortex. To address this, I first induce a shift in OD with 3 days of MD and then use several pharmacological methods to shut off cortical inhibitory synaptic transmission. I demonstrate that rapid deprived-eye depression is strongly expressed at excitatory thalamocortical synapses without any influences of polysynaptic intracortical inhibition. In the second part of my work, I try to resolve the nature/identity of the molecular mechanism that underlies the regulation of [theta]m. Using a transgenic mouse model, I find that a reduction in the NR2A/B subunit ratio of the N-methyl-d-aspartate (NMDA) receptor during MD alters the qualities of OD plasticity by impairing weakening of deprived-eye inputs and enhancing strengthening of open-eye inputs. These findings suggest that NMDAR subunit composition may specify the value and the rate of adjustment of synaptic 0m, which in turn determines the bidirectional cortical response to MD. The final portion of my thesis addresses the factors that limit OD plasticity beyond the critical period. I test the hypothesis that the developmental increase in intracortical GABAergic inhibitory synaptic transmission is a fundamental restricting factor for adult cortical plasticity and demonstrate that parvalbumin-expressing fast-spiking basket cells are specifically implicated in the absence of juvenile-like deprived-eye depression in adult mice.
by Lena A. Khibnik.
Ph.D.
48
Phillips, Marnie A. (Marnie Ann). "Eye-opening and control of visual synapse development in the mouse superior colliculus." Thesis, Massachusetts Institute of Technology, 2007. http://hdl.handle.net/1721.1/39005.
Full textAbstract:
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2007."June 2007."
Includes bibliographical references.
The mammalian superior colliculus (SC) coordinates visual, somatosensory, and auditory stimuli to guide animal behavior. The superficial layers (sSC) receive visual information via two major afferent projections: 1) A direct retinal projection and 2) an indirect projection from Layer V visual cortex. The retinal projection reaches the rat sSC by embryonic day 16, is topographic, and refines to form a high resolution map of visual space early in development, before eye-opening in rodents (-P12-P14). The cortical projection is delayed by about eight days, just reaching the sSC around P4, and does not complete its topographic refinement until around the time of eye-opening. These afferents compete for synaptic space during a time when patterns of spontaneous and evoked activity are rapidly changing. I have used the mouse sSC as a model system to test the role of new activity patterns due to the initial onset of visual experience after eye-opening in visual synaptic development. I have described the organization of retinal and cortical afferents and the laminar organization of the mouse sSC in Chapter 3. Previous work demonstrated eye-opening (EO) induces the appearance of dendritic PSD-95 and LTP in the sSC within 2-4 hours.
(cont.) I provide evidence that EO-induced PSD-95 trafficking is required for the stabilization of new synapses in vivo as a result of patterned visual experience after eye-opening. mEPSC frequency recorded in a vertical neuronal subtype of the mid-SGS increases at least three-fold after eye-opening, indicating a rapid synaptogenesis that does not occur in PSD95KO mice, or in age-matched littermates deprived of initial visual experience. A structural analysis of these neurons revealed caliber-specific patterns of spine and filopodia development that depend on EO and the projection from visual cortex. Between P11 and P13, dendrites post-synaptic to cortical axons undergo an EO-independent tripling of filopodial density and an EO-dependent maintenance of dendritic spine density. These data suggest that rapid vision-induced trafficking of PSD-95 enables long-term potentiation and stabilization of newly formed cortico-collicular synapses in response to patterned visual stimuli. Furthermore, these data suggest that cortical inputs are sensitive to pattern vision deprivation between P12 and P13, but retinal inputs are not.
by Marnie A. Phillips.
Ph.D.
49
Espeso, Gil Sergio 1985. "The mouse cortex regulome. Effects of environmental enrichment on postnatal brain development." Doctoral thesis, Universitat Pompeu Fabra, 2016. http://hdl.handle.net/10803/552941.
Full textAbstract:
El reguloma està constituït per un sistema complex de factors que controlen el fenotip molecular de la cèl·lula, que al seu torn està influenciada pel medi ambient. Qualsevol pertorbació pot desencadenar canvis que poden implicar una regulació disfuncional. El cervell integra constantment una quantitat considerable d’informació motora, sensorial i cognitiva. Aquesta integració és particularment important en el desenvolupament postnatal, en què el cervell ha d'establir els compromisos moleculars necessaris per adaptar-se a un entorn canviant. L'objectiu d'aquest estudi és investigar com els factors ambientals poden influenciar en el reguloma de l'escorça cerebral durant el desenvolupament postnatal. Per tal d'estudiar la interacció entre el reguloma i el medi ambient, s’ha utilitzat el paradigma d'enriquiment ambiental en què s’exposa els ratolins a estímuls freqüentment canviants de manera constant durant un mes. En aquest estudi s'ha emprat seqüenciació d'última generació per poder analitzar l'epigenoma, regions obertes de la cromatina, interaccions cromosòmiques, el transcriptoma i el proteoma. En particular, s’observen canvis dinàmics en la cobertura de la modificació H3K79me2 neuronal, juntament amb un augment general d'accessibilitat en regions promotores i enhancers associats a gens importants per a l'aprenentatge. Complementàriament, les dades de transcriptòmica i proteòmica recolzen aquests resultats. Així mateix, s’ha implementat una estratègia particular en citometria de flux que ha permès esbrinar quines són les majors diferències en els canvis induïts per l'enriquiment ambiental en l'escorça cerebral i neurones corticals. En conjunt, i per primer cop, aquests estudis apunten que l'enriquiment ambiental indueix una sèrie de canvis en els mecanismes de regulació de les neurones corticals, relacionats amb un minuciós ajust sinàptic durant el desenvolupament postnatal.The regulome constitutes a complex system of factors that control the molecular phenotype of the cell, which is influenced by the environment. Any disturbance can trigger a set of changes involving dysfunctional regulation. The brain constantly integrates a multitude of motor, sensory and cognitive information. This engagement is particularly important in postnatal development when the brain must establish the molecular commitments needed to adapt to a changing environment. The aim of this study is to investigate how environmental factors influence the cerebral cortex regulome during postnatal development. In order to study the interaction between the regulome and the environment, we used the paradigm of environmental enrichment (EE) in which mice received constant and novel stimulation during a month. Next Generation Sequencing (NGS) –based techniques were employed to analyze the epigenome, gene accessibility, chromosomal interactions, the transcriptome and the proteome. Notably, dynamic changes in neuronal H3K79me2 coverage were observed, together with a general gain of promoter and enhancer accessibility of learning-associated genes. These changes were also supported by transcriptomic and proteomic data. We followed a flow cytometry strategy that allowed us to highlight differences in EE-induced changes in the cerebral cortex and cortical neurons. Our research reveals for the first time that EE induces changes in the regulatory mechanisms related with synaptic fine-tuning in cortical neurons during postnatal development.
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Hazy, Amanda Dawn. "Novel Immune-Regulatory Mechanisms in a Mouse Model of Traumatic Brain Injury." Thesis, Virginia Tech, 2019. http://hdl.handle.net/10919/102505.
Full textAbstract:
Traumatic brain injury (TBI) is a major health concern in the United States and worldwide and effective treatment options are limited. Differences in the magnitude and characteristics of the peripheral-derived immune cell response to TBI are key contributors to the secondary cascades of damage following brain trauma, and means of modifying this response to improve clinical outcome are a current area of active research. Our work elucidated the peripheral immune response to TBI by characterizing the transcriptomic profile of juvenile vs adult peripheral immune cells following TBI as well as discovering a novel role for the tyrosine kinase receptor EphA4 in the peripheral-derived immune response to brain trauma. Previous work has demonstrated significant differences in recovery from TBI in young vs adult animals, and some studies have indicated that the immune response contributes to these differences. We utilized next-generation sequencing to compare gene expression profiles of blood cell fraction samples in juvenile and adult mice. Our work demonstrated that juvenile peripheral immune cells show a more dynamic response to TBI than adult and that pattern recognition receptor signaling is a cornerstone of these differences. To assess the specific mechanisms involved in the peripheral response to TBI, we utilized a bone marrow chimeric mouse model lacking EphA4 in the hematopoietic compartment. These studies found decreased lesion infiltration of peripheral immune cells, specifically activated macrophages, in the absence of EphA4. We also showed that EphA4 interacts with the Tie2/Angiopoietin signaling axis to regulate macrophage phenotype on the M1/2 continuum. Overall, our work demonstrated a novel role for EphA4, mediated by Tie2, as a pro-inflammatory regulator of the peripheral-derived immune cell response to TBI.