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Статті в журналах з теми "Fast Spiking Interneurons (FSINs)"

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Higgs, Matthew H., and Charles J. Wilson. "Frequency-dependent entrainment of striatal fast-spiking interneurons." Journal of Neurophysiology 122, no. 3 (September 1, 2019): 1060–72. http://dx.doi.org/10.1152/jn.00369.2019.

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Striatal fast-spiking interneurons (FSIs) fire in variable-length runs of action potentials at 20–200 spikes/s separated by pauses. In vivo, or with fluctuating applied current, both runs and pauses become briefer and more variable. During runs, spikes are entrained specifically to gamma-frequency components of the input fluctuations. We stimulated parvalbumin-expressing striatal FSIs in mouse brain slices with broadband noise currents added to direct current steps and measured spike entrainment across all frequencies. As the constant current level was increased, FSIs produced longer runs and showed sharper frequency tuning, with best entrainment at the stimulus frequency matching their intrarun firing rate. We separated the contributions of previous spikes from that of the fluctuating stimulus, revealing a strong contribution of previous action potentials to gamma-frequency entrainment. In contrast, after subtraction of the effect inherited from the previous spike, the remaining stimulus contribution to spike generation was less sharply tuned, showing a larger contribution of lower frequencies. The frequency specificity of entrainment within a run was reproduced with a phase resetting model based on experimentally measured phase resetting curves of the same FSIs. In the model, broadly tuned phase entrainment for the first spike in a run evolved into sharply tuned gamma entrainment over the next few spikes. The data and modeling results indicate that for FSIs firing in brief runs and pauses firing within runs is entrained by gamma-frequency components of the input, whereas the onset timing of runs may be sensitive to a wider range of stimulus frequency components. NEW & NOTEWORTHY Specific types of neurons entrain their spikes to particular oscillation frequencies in their synaptic input. This entrainment is commonly understood in terms of the subthreshold voltage response, but how this translates to spiking is not clear. We show that in striatal fast-spiking interneurons, entrainment to gamma-frequency input depends on rhythmic spike runs and is explained by the phase resetting curve, whereas run initiation can be triggered by a broad range of input frequencies.
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Marche, Kévin, and Paul Apicella. "Changes in activity of fast-spiking interneurons of the monkey striatum during reaching at a visual target." Journal of Neurophysiology 117, no. 1 (January 1, 2017): 65–78. http://dx.doi.org/10.1152/jn.00566.2016.

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Recent works highlight the importance of local inhibitory interneurons in regulating the function of the striatum. In particular, fast-spiking interneurons (FSIs), which likely correspond to a subgroup of GABAergic interneurons, have been involved in the control of movement by exerting strong inhibition on striatal output pathways. However, little is known about the exact contribution of these presumed interneurons in movement preparation, initiation, and execution. We recorded the activity of FSIs in the striatum of monkeys as they performed reaching movements to a visual target under two task conditions: one in which the movement target was presented at unsignaled left or right locations, and another in which advance information about target location was available, thus allowing monkeys to react faster. Modulations of FSI activity around the initiation of movement (53% of 55 neurons) consisted mostly of increases reaching maximal firing immediately before or, less frequently, after movement onset. Another subset of FSIs showed decreases in activity during movement execution. Rarely did movement-related changes in FSI firing depend on response direction and movement speed. Modulations of FSI activity occurring relatively early in relation to movement initiation were more influenced by the preparation for movement, compared with those occurring later. Conversely, FSI activity remained unaffected, as monkeys were preparing a movement toward a specific location and instead moved to the opposite direction when the trigger occurred. These results provide evidence that changes in activity of presumed GABAergic interneurons of the primate striatum could make distinct contributions to processes involved in movement generation. NEW & NOTEWORTHY We explored the functional contributions of striatal fast-spiking interneurons (FSIs), presumed GABAergic interneurons, to distinct steps of movement generation in monkeys performing a reaching task. The activity of individual FSIs was modulated before and during the movement, consisting mostly of increased in firing rates. Changes in activity also occurred during movement preparation. We interpret this variety of modulation types at different moments of task performance as reflecting differential FSI control over distinct phases of movement.
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Banaie Boroujeni, Kianoush, Mariann Oemisch, Seyed Alireza Hassani, and Thilo Womelsdorf. "Fast spiking interneuron activity in primate striatum tracks learning of attention cues." Proceedings of the National Academy of Sciences 117, no. 30 (July 13, 2020): 18049–58. http://dx.doi.org/10.1073/pnas.2001348117.

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Cognitive flexibility depends on a fast neural learning mechanism for enhancing momentary relevant over irrelevant information. A possible neural mechanism realizing this enhancement uses fast spiking interneurons (FSIs) in the striatum to train striatal projection neurons to gate relevant and suppress distracting cortical inputs. We found support for such a mechanism in nonhuman primates during the flexible adjustment of visual attention in a reversal learning task. FSI activity was modulated by visual attention cues during feature-based learning. One FSI subpopulation showed stronger activation during learning, while another FSI subpopulation showed response suppression after learning, which could indicate a disinhibitory effect on the local circuit. Additionally, FSIs that showed response suppression to learned attention cues were activated by salient distractor events, suggesting they contribute to suppressing bottom-up distraction. These findings suggest that striatal fast spiking interneurons play an important role when cues are learned that redirect attention away from previously relevant to newly relevant visual information. This cue-specific activity was independent of motor-related activity and thus tracked specifically the learning of reward predictive visual features.
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Damodaran, Sriraman, Rebekah C. Evans, and Kim T. Blackwell. "Synchronized firing of fast-spiking interneurons is critical to maintain balanced firing between direct and indirect pathway neurons of the striatum." Journal of Neurophysiology 111, no. 4 (February 15, 2014): 836–48. http://dx.doi.org/10.1152/jn.00382.2013.

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The inhibitory circuits of the striatum are known to be critical for motor function, yet their contributions to Parkinsonian motor deficits are not clear. Altered firing in the globus pallidus suggests that striatal medium spiny neurons (MSN) of the direct (D1 MSN) and indirect pathway (D2 MSN) are imbalanced during dopamine depletion. Both MSN classes receive inhibitory input from each other and from inhibitory interneurons within the striatum, specifically the fast-spiking interneurons (FSI). To investigate the role of inhibition in maintaining striatal balance, we developed a biologically-realistic striatal network model consisting of multicompartmental neuron models: 500 D1 MSNs, 500 D2 MSNs and 49 FSIs. The D1 and D2 MSN models are differentiated based on published experiments of individual channel modulations by dopamine, with D2 MSNs being more excitable than D1 MSNs. Despite this difference in response to current injection, in the network D1 and D2 MSNs fire at similar frequencies in response to excitatory synaptic input. Simulations further reveal that inhibition from FSIs connected by gap junctions is critical to produce balanced firing. Although gap junctions produce only a small increase in synchronization between FSIs, removing these connections resulted in significant firing differences between D1 and D2 MSNs, and balanced firing was restored by providing synchronized cortical input to the FSIs. Together these findings suggest that desynchronization of FSI firing is sufficient to alter balanced firing between D1 and D2 MSNs.
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Bakhurin, Konstantin I., Victor Mac, Peyman Golshani, and Sotiris C. Masmanidis. "Temporal correlations among functionally specialized striatal neural ensembles in reward-conditioned mice." Journal of Neurophysiology 115, no. 3 (March 1, 2016): 1521–32. http://dx.doi.org/10.1152/jn.01037.2015.

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Анотація:
As the major input to the basal ganglia, the striatum is innervated by a wide range of other areas. Overlapping input from these regions is speculated to influence temporal correlations among striatal ensembles. However, the network dynamics among behaviorally related neural populations in the striatum has not been extensively studied. We used large-scale neural recordings to monitor activity from striatal ensembles in mice undergoing Pavlovian reward conditioning. A subpopulation of putative medium spiny projection neurons (MSNs) was found to discriminate between cues that predicted the delivery of a reward and cues that predicted no specific outcome. These cells were preferentially located in lateral subregions of the striatum. Discriminating MSNs were more spontaneously active and more correlated than their nondiscriminating counterparts. Furthermore, discriminating fast spiking interneurons (FSIs) represented a highly prevalent group in the recordings, which formed a strongly correlated network with discriminating MSNs. Spike time cross-correlation analysis showed the existence of synchronized activity among FSIs and feedforward inhibitory modulation of MSN spiking by FSIs. These findings suggest that populations of functionally specialized (cue-discriminating) striatal neurons have distinct network dynamics that sets them apart from nondiscriminating cells, potentially to facilitate accurate behavioral responding during associative reward learning.
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Govindaiah, Gubbi, Rong-Jian Liu, and Yanyan Wang. "Dopamine D2L Receptor Deficiency Alters Neuronal Excitability and Spine Formation in Mouse Striatum." Biomedicines 10, no. 1 (January 4, 2022): 101. http://dx.doi.org/10.3390/biomedicines10010101.

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The striatum contains several types of neurons including medium spiny projection neurons (MSNs), cholinergic interneurons (ChIs), and fast-spiking interneurons (FSIs). Modulating the activity of these neurons by the dopamine D2 receptor (D2R) can greatly impact motor control and movement disorders. D2R exists in two isoforms: D2L and D2S. Here, we assessed whether alterations in the D2L and D2S expression levels affect neuronal excitability and synaptic function in striatal neurons. We observed that quinpirole inhibited the firing rate of all three types of striatal neurons in wild-type (WT) mice. However, in D2L knockout (KO) mice, quinpirole enhanced the excitability of ChIs, lost influence on spike firing of MSNs, and remained inhibitory effect on spike firing of FSIs. Additionally, we showed mIPSC frequency (but not mIPSC amplitude) was reduced in ChIs from D2L KO mice compared with WT mice, suggesting spontaneous GABA release is reduced at GABAergic terminals onto ChIs in D2L KO mice. Furthermore, we found D2L deficiency resulted in reduced dendritic spine density in ChIs, suggesting D2L activation plays a role in the formation/maintenance of dendritic spines of ChIs. These findings suggest new molecular and cellular mechanisms for causing ChIs abnormality seen in Parkinson’s disease or drug-induced dyskinesias.
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Xiao, Guihua, Yilin Song, Yu Zhang, Yu Xing, Shengwei Xu, Mixia Wang, Junbo Wang, Deyong Chen, Jian Chen, and Xinxia Cai. "Dopamine and Striatal Neuron Firing Respond to Frequency-Dependent DBS Detected by Microelectrode Arrays in the Rat Model of Parkinson’s Disease." Biosensors 10, no. 10 (September 28, 2020): 136. http://dx.doi.org/10.3390/bios10100136.

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(1) Background: Deep brain stimulation (DBS) is considered as an efficient treatment method for alleviating motor symptoms in Parkinson’s disease (PD), while different stimulation frequency effects on the specific neuron patterns at the cellular level remain unknown. (2) Methods: In this work, nanocomposites-modified implantable microelectrode arrays (MEAs) were fabricated to synchronously record changes of dopamine (DA) concentration and striatal neuron firing in the striatum during subthalamic nucleus DBS, and different responses of medium spiny projecting neurons (MSNs) and fast spiking interneurons (FSIs) to DBS were analyzed. (3) Results: DA concentration and striatal neuron spike firing rate showed a similar change as DBS frequency changed from 10 to 350 Hz. Note that the increases in DA concentration (3.11 ± 0.67 μM) and neural spike firing rate (15.24 ± 2.71 Hz) were maximal after the stimulation at 100 Hz. The MSNs firing response to DBS was significant, especially at 100 Hz, while the FSIs remained stable after various stimulations. (4) Conclusions: DBS shows the greatest regulatory effect on DA concentration and MSNs firing rate at 100 Hz stimulation. This implantable MEA in the recording of the neurotransmitter and neural spike pattern response to DBS provides a new insight to understand the mechanism of PD at the cellular level.
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Shaheen, Hina, and Roderick Melnik. "Deep Brain Stimulation with a Computational Model for the Cortex-Thalamus-Basal-Ganglia System and Network Dynamics of Neurological Disorders." Computational and Mathematical Methods 2022 (February 13, 2022): 1–17. http://dx.doi.org/10.1155/2022/8998150.

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Анотація:
Deep brain stimulation (DBS) can alleviate the movement disorders like Parkinson’s disease (PD). Indeed, it is known that aberrant beta (13-30 Hz) oscillations and the loss of dopaminergic neurons in the basal ganglia-thalamus (BGTH) and cortex characterize the akinesia symptoms of PD. However, the relevant biophysical mechanism behind this process still remains unclear. Based on the prior striatal inhibitory model, we propose an extended BGTH model incorporating medium spine neurons (MSNs) and fast-spiking interneurons (FSIs) along with the effect of DBS. We are focusing in this paper on an open-loop DBS mode, where the stimulation parameters stay constant independent of variations in the disease state, and modifications of parameters rely mainly on trial and error of medical experts. Additionally, we propose a novel combined model of the cerebellar-basal-ganglia thalamocortical network, MSNs, and FSIs and show new results that indicate that Parkinsonian oscillations in the beta-band frequency range emerge from the dynamics of such a network. Our model predicts that DBS can be used to suppress beta oscillations in globus pallidus pars interna (GPi) neurons. This research will help our better understanding of the changes in the brain activity caused by DBS, providing new insight for studying PD in the future.
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Kunimatsu, Jun, Shinya Yamamoto, Kazutaka Maeda, and Okihide Hikosaka. "Environment-based object values learned by local network in the striatum tail." Proceedings of the National Academy of Sciences 118, no. 4 (January 19, 2021): e2013623118. http://dx.doi.org/10.1073/pnas.2013623118.

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Basal ganglia contribute to object-value learning, which is critical for survival. The underlying neuronal mechanism is the association of each object with its rewarding outcome. However, object values may change in different environments and we then need to choose different objects accordingly. The mechanism of this environment-based value learning is unknown. To address this question, we created an environment-based value task in which the value of each object was reversed depending on the two scene-environments (X and Y). After experiencing this task repeatedly, the monkeys became able to switch the choice of object when the scene-environment changed unexpectedly. When we blocked the inhibitory input from fast-spiking interneurons (FSIs) to medium spiny projection neurons (MSNs) in the striatum tail by locally injecting IEM-1460, the monkeys became unable to learn scene-selective object values. We then studied the mechanism of the FSI-MSN connection. Before and during this learning, FSIs responded to the scenes selectively, but were insensitive to object values. In contrast, MSNs became able to discriminate the objects (i.e., stronger response to good objects), but this occurred clearly in one of the two scenes (X or Y). This was caused by the scene-selective inhibition by FSI. As a whole, MSNs were divided into two groups that were sensitive to object values in scene X or in scene Y. These data indicate that the local network of striatum tail controls the learning of object values that are selective to the scene-environment. This mechanism may support our flexible switching behavior in various environments.
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Bryson, Alexander, Samuel F. Berkovic, Steven Petrou, and David B. Grayden. "State transitions through inhibitory interneurons in a cortical network model." PLOS Computational Biology 17, no. 10 (October 15, 2021): e1009521. http://dx.doi.org/10.1371/journal.pcbi.1009521.

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Inhibitory interneurons shape the spiking characteristics and computational properties of cortical networks. Interneuron subtypes can precisely regulate cortical function but the roles of interneuron subtypes for promoting different regimes of cortical activity remains unclear. Therefore, we investigated the impact of fast spiking and non-fast spiking interneuron subtypes on cortical activity using a network model with connectivity and synaptic properties constrained by experimental data. We found that network properties were more sensitive to modulation of the fast spiking population, with reductions of fast spiking excitability generating strong spike correlations and network oscillations. Paradoxically, reduced fast spiking excitability produced a reduction of global excitation-inhibition balance and features of an inhibition stabilised network, in which firing rates were driven by the activity of excitatory neurons within the network. Further analysis revealed that the synaptic interactions and biophysical features associated with fast spiking interneurons, in particular their rapid intrinsic response properties and short synaptic latency, enabled this state transition by enhancing gain within the excitatory population. Therefore, fast spiking interneurons may be uniquely positioned to control the strength of recurrent excitatory connectivity and the transition to an inhibition stabilised regime. Overall, our results suggest that interneuron subtypes can exert selective control over excitatory gain allowing for differential modulation of global network state.
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Дисертації з теми "Fast Spiking Interneurons (FSINs)"

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Whittaker, Maximilian Anthony Erik. "Modulation of fast-spiking interneurons using two-pore channel blockers." Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31252.

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The balance between excitatory and inhibitory synaptic transmission within and across neurons in active networks is crucial for cortical function and may allow for rapid transitions between stable network states. GABAergic interneurons mediate the majority of inhibitory transmission in the cortex, and therefore contribute to the global balance of activity in neuronal networks. Disruption in the network balance due to impaired inhibition has been implicated in several neuropsychiatric diseases (Marin 2012). Both schizophrenia and autism are two highly heritable cognitive disorders with complex genetic aetiologies but overlapping behavioural phenotypes that share common imbalances in neuronal network activity (Gao & Penzes 2015). An increasing body of evidence suggests that functional abnormalities in a particular group of cortical GABAergic interneurons expressing the calcium-binding protein parvalbumin (PV) are involved in the pathology of these disorders (Marin 2012). As deficits in this neuronal population have been linked to these disorders it could be useful to target them and increase their activity. A conserved feature in PV cells is their unusually low input resistance compared to other neuronal populations. This feature is regulated by the expression of leak K+ channels, believed to be mediated in part by TASK and TREK subfamily two-pore K+ channels (Goldberg et al. 2011). The selective blockade of specific leak K+ channels could therefore be applied to increase the activity of PV cells. In this thesis, specific TASK-1/3 and TREK-1 channel blockers were applied in cortical mouse slices in an attempt to increase the output of PV cells. The blockade of either channel did not successfully increase the amplitude of PV cell-evoked inhibitory postsynaptic currents (IPSCs) onto principal cells. However, while the blockade of TASK-1/3 channels failed to depolarise the membrane or alter the input resistance, the blockade of TREK-1 channels resulted in a small but significant depolarisation of the membrane potential in PV cells. Interestingly, TREK-1 channel blockade also increased action potential firing of PV cells in response to given current stimuli, suggesting that TREK-1 could be a useful target for PV cell modulation. These results demonstrate for the first time the functional effects of using specific two-pore K+ channel blockers in PV cells. Furthermore, these data provide electrophysiological evidence against the functional expression of TASK-1/3 in PV cells. It could therefore be interesting to further characterise the precise subtypes of leak K+ channels responsible for their low resistivity. This would help to classify the key contributors of the background K+ conductances present in PV cells in addition to finding suitable targets to increase their activity.
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Albieri, Giorgia. "The role of fast-spiking interneurons in cortical map plasticity." Thesis, King's College London (University of London), 2013. https://kclpure.kcl.ac.uk/portal/en/theses/the-role-of-fastspiking-interneurons-in-cortical-map-plasticity(3d7b76ff-1833-4147-addd-6f24accbd6cc).html.

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Rodents have a topographic map in primary somatosensory cortex of the contralateral facial whiskers. A brief period of whisker trimming causes the representation of the nontrimmed whiskers (spared) to expand into the cortex that has lost its principal sensory input (deprived). It has been hypothesized that this is mediated by a period of persistent disinhibition in deprived cortex that enables the expansion of spared whisker representations. Alternatively, it has been proposed that inhibition undergoes a biphasic change with an initial, brief period of disinhibition to promote plasticity in excitatory circuits followed by a more prolonged increase in inhibition to re-establish the excitatory – inhibitory balance. These hypotheses make different predictions about how inhibition changes during cortical map plasticity, which I have tested in this thesis. I focused on fast-spiking (FS) interneurons, which are thought to play an important role in adult cortical plasticity. I made electrophysiological recordings in layer 2/3 to determine how inhibitory circuitry in deprived cortex is affected by whisker deprivation. The amplitude of miniature excitatory postsynaptic potentials (mEPSPs) in deprived FS interneurons was increased with no change in mEPSP frequency suggesting that the global excitatory drive onto FS interneurons was potentiated. In contrast, the amplitude of miniature inhibitory postsynaptic currents (mIPSCs) in layer 2/3 pyramidal neurons was unchanged, but there was a small but significant increase in mIPSC frequency. I investigated feedback inhibitory circuits in more detail by recording from pairs of pyramidal cells and FS interneurons that were synaptically-connected. Surprisingly, I found that the strength of local excitation onto FS interneurons and the strength of FS – mediated inhibition on deprived pyramidal neurons were unchanged. I concluded that, contrary to two popular hypotheses, a brief period of sensory deprivation did not alter the feedback inhibition in layer 2/3 of deprived cortex.
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Papasavvas, Christoforos A. "Investigating the role of fast-spiking interneurons in neocortical dynamics." Thesis, University of Newcastle upon Tyne, 2017. http://hdl.handle.net/10443/3808.

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Fast-spiking interneurons are the largest interneuronal population in neocortex. It is well documented that this population is crucial in many functions of the neocortex by subserving all aspects of neural computation, like gain control, and by enabling dynamic phenomena, like the generation of high frequency oscillations. Fast-spiking interneurons, which represent mainly the parvalbumin-expressing, soma-targeting basket cells, are also implicated in pathological dynamics, like the propagation of seizures or the impaired coordination of activity in schizophrenia. In the present thesis, I investigate the role of fast-spiking interneurons in such dynamic phenomena by using computational and experimental techniques. First, I introduce a neural mass model of the neocortical microcircuit featuring divisive inhibition, a gain control mechanism, which is thought to be delivered mainly by the soma-targeting interneurons. Its dynamics were analysed at the onset of chaos and during the phenomena of entrainment and long-range synchronization. It is demonstrated that the mechanism of divisive inhibition reduces the sensitivity of the network to parameter changes and enhances the stability and exibility of oscillations. Next, in vitro electrophysiology was used to investigate the propagation of activity in the network of electrically coupled fast-spiking interneurons. Experimental evidence suggests that these interneurons and their gap junctions are involved in the propagation of seizures. Using multi-electrode array recordings and optogenetics, I investigated the possibility of such propagating activity under the conditions of raised extracellular K+ concentration which applies during seizures. Propagated activity was recorded and the involvement of gap junctions was con rmed by pharmacological manipulations. Finally, the interaction between two oscillations was investigated. Two oscillations with di erent frequencies were induced in cortical slices by directly activating the pyramidal cells using optogenetics. Their interaction suggested the possibility of a coincidence detection mechanism at the circuit level. Pharmacological manipulations were used to explore the role of the inhibitory interneurons during this phenomenon. The results, however, showed that the observed phenomenon was not a result of synaptic activity. Nevertheless, the experiments provided some insights about the excitability of the tissue through scattered light while using optogenetics. This investigation provides new insights into the role of fast-spiking interneurons in the neocortex. In particular, it is suggested that the gain control mechanism is important for the physiological oscillatory dynamics of the network and that the gap junctions between these interneurons can potentially contribute to the inhibitory restraint during a seizure.
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GIORDANO, Nadia Concetta. "Early, sustained and broadly-tuned discharge of fast-spiking interneurons in the premotor cortex during action planning." Doctoral thesis, Scuola Normale Superiore, 2021. http://hdl.handle.net/11384/106386.

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Preparatory neural activity in premotor areas is critical for planning and execution of voluntary movements. Previous studies in monkeys and mice have revealed how the discharges of pyramidal, excitatory neurons (PNs) encode a motor plan for an upcoming movement (Afshar et al., 2011; Chen et al., 2017; Li et al., 2015). However, the contribution of GABAergic interneurons, specifically fast-spiking interneurons (FSNs), to voluntary movements remains poorly understood. Putative premotor areas involved in action planning have been demonstrated in rodents. In particular, in mice, a premotor area controlling voluntary licking has been identified in the anterior-lateral motor cortex (ALM) (Komiyama et al., 2010). Also, ALM partially overlaps with the rostral forelimb area (RFA), the previously defined premotor region involved in the control of paw movement in rats and mice (Rouiller et al., 1993; Tennant et al., 2011). To understand the excitatory-inhibitory microcircuit involved in action planning, here I compare directly the response properties of PNs and FSNs during licking behaviour and forelimb retraction in the mouse. Recordings are carried out with both acute electrodes and chronic microelectrode arrays from both the two premotor areas, i.e. the ALM – responsible for licking –, and RFA – involved in paw movement. Specifically, in a first set of experiments, I used head-restrained mice that spontaneously lick a reward delivered at random intervals from a drinking spout. Mice voluntary performed either single isolated or a burst of consecutive licks, which I categorized, a posteriori, in single (= 1 lick) and multiple licks (≥ 3 licks). During the task, I extracellularly recorded single units’ activity from ALM, using acute in vivo electrophysiology. I identified putative PNs and FSNs, based on well-established features of their waveforms, and investigated their functional properties during the movement. Unexpectedly, I report that optogenetically-verified FSNs showed an earlier and more sustained activation than PNs. In particular, most of the neurons’ activity anticipated the licking onset, consistently with an involvement of the ALM in movement planning. The majority of the neurons (~90%) increased their firing frequency in correspondence with the movement, but suppressive modulations were also observed in a subset of units. For both PNs and FSNs, I found significantly greater discharge during multiple than single licks and the peak discharge was significantly delayed for both subclasses during multiple licking events. However, FSNs modulated their activity about 100ms earlier than PNs. Furthermore, almost all FSNs showed a peak in their response before the beginning of the sequence of licks. Analysis of mean information content confirms that FSNs predict licking onset not only significantly better, but even earlier, than PNs. Chronic electrode arrays covering both the ALM and RFA were next used to simultaneously probe neural responses during (i) licking and (ii) forelimb pulling in a robotic device (Spalletti et al., 2017). I report that most of the FSNs respond with a stereotyped increase in their firing rates during both licking and pulling. In stark contrast, PNs show a variety of behaviours, dependent on movement type. At least for a minority of them, licking behaviour and forelimb retraction are represented as two different motor acts, reaching significant levels in the PNs. Accordingly, computational analysis shows that PNs carry more independent information than FSNs. Altogether, these data indicate that a global rise of GABAergic inhibition mediated by FSNs firing contributes to early action planning. Next, encouraged by the deeper understanding of the cortical microcircuits underlying movement planning in mice, I exploited this knowledge to explore more complex mechanisms, as action understanding. The neural circuits that integrate performed and observed actions have been found in the premotor cortex of monkeys and named as ‘mirror neurons system’ (di Pellegrino et al., 1992). Recently, the presence of mirror neurons have been demonstrated in rodents in the anterior cingulate cortex (Carrillo et al., 2019), but whether they could contribute to action understanding in the premotor cortex is still unclear. At behavioural level, the observation of actions can actually lead, in some cases, to the repetition of those same actions. This phenomenon has been named social facilitation, and the underlying motor program has been attributed to the mirror system (Ferrari et al., 2005). Here, I set up a behavioural task similar to the one exploited in monkeys to explore social facilitation in mice. I took advantage of licking behaviour to set up the social facilitation experiment. Therefore, head-restrained mice were allowed to lick water from a feeding needle. I found that mice can actually facilitated to lick more when another individual was engaged in the same action, supporting the hypothesis of a social facilitation in mouse. Altogether these results indicate that the observers’ behaviour was actually influenced by the demonstrators’ one, laying the groundwork for the study of mirror neurons in mice at cellular level.
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Sivarajan, Vishalini [Verfasser], Dirk [Akademischer Betreuer] Feldmeyer, and Björn M. [Akademischer Betreuer] Kampa. "Morphological and functional characterisation of non-fast spiking interneurons in layer 4 microcircuitry of rat barrel cortex / Vishalini Sivarajan ; Dirk Feldmeyer, Björn M. Kampa." Aachen : Universitätsbibliothek der RWTH Aachen, 2017. http://d-nb.info/1158667817/34.

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Hjorth, Johannes. "Computer Modelling of Neuronal Interactions in the Striatum." Doctoral thesis, KTH, Beräkningsbiologi, CB, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-10523.

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Large parts of the cortex and the thalamus project into the striatum,which serves as the input stage of the basal ganglia. Information isintegrated in the striatal neural network and then passed on, via themedium spiny (MS) projection neurons, to the output stages of thebasal ganglia. In addition to the MS neurons there are also severaltypes of interneurons in the striatum, such as the fast spiking (FS)interneurons. I focused my research on the FS neurons, which formstrong inhibitory synapses onto the MS neurons. These striatal FSneurons are sparsely connected by electrical synapses (gap junctions),which are commonly presumed to synchronise their activity.Computational modelling with the GENESIS simulator was used toinvestigate the effect of gap junctions on a network of synapticallydriven striatal FS neurons. The simulations predicted a reduction infiring frequency dependent on the correlation between synaptic inputsto the neighbouring neurons, but only a slight synchronisation. Thegap junction effects on modelled FS neurons showing sub-thresholdoscillations and stuttering behaviour confirm these results andfurther indicate that hyperpolarising inputs might regulate the onsetof stuttering.The interactions between MS and FS neurons were investigated byincluding a computer model of the MS neuron. The hypothesis was thatdistal GABAergic input would lower the amplitude of back propagatingaction potentials, thereby reducing the calcium influx in thedendrites. The model verified this and further predicted that proximalGABAergic input controls spike timing, but not the amplitude ofdendritic calcium influx after initiation.Connecting models of neurons written in different simulators intonetworks raised technical problems which were resolved by integratingthe simulators within the MUSIC framework. This thesis discusses theissues encountered by using this implementation and gives instructionsfor modifying MOOSE scripts to use MUSIC and provides guidelines forachieving compatibility between MUSIC and other simulators.This work sheds light on the interactions between striatal FS and MSneurons. The quantitative results presented could be used to developa large scale striatal network model in the future, which would beapplicable to both the healthy and pathological striatum.
QC 20100720
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Rühlmann, Charlotta [Verfasser], Bernhard [Akademischer Betreuer] Hemmer, and Achim [Akademischer Betreuer] Berthele. "The NMDA-Receptor on Fast Spiking Parvalbumin-expressing Interneurons : Investigations on the Role of Disinhibition and its Effects on Gamma Oscillations, Cognitive Functions and Symptoms of Schizophrenia in a Mouse Model / Charlotta Rühlmann. Gutachter: Bernhard Hemmer ; Achim Berthele. Betreuer: Bernhard Hemmer." München : Universitätsbibliothek der TU München, 2014. http://d-nb.info/1053467680/34.

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Dasgupta, Dabanjan. "Plasticity of Intrinsic Excitability in Fast Spiking Interneurons of the Dentate Gyrus & Its Implications for Neuronal Network Dynamics." Thesis, 2015. https://etd.iisc.ac.in/handle/2005/4079.

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Inhibitory GABAergic neurons, although forming a minor proportion of the neuronal population in the central nervous system, have been reported to be crucial for different physiological states of the brain. Among the vast diversity of this neuronal subpopulation, the fast spiking interneurons (FSINs) have been studied in great detail owing to their morphological and physiological attributes and functional correlates. Due to their perisomatic targeting and rapid spiking nature, they have been strongly associated with spike time and gain control of their target neurons in neuronal microcircuits across different regions of the brain. Plastic alterations of neuronal synaptic and intrinsic properties have been associated with learning and memory. However, a vast majority of the studies performed so far pertains to excitatory neurons. Although some recent studies have looked into plasticity of inhibition, little is known about plastic changes in the inhibitory neurons. Owing to the morpho-physiological properties of the FSINs and their massive connectivity, plastic alterations in them can cascade to their connected neuronal microcircuit. The dentate gyrus (DG) forms an important gateway of information for the hippocampus and has been associated with pattern separation. The granule cells which are predominantly known to target interneurons discharge in the gamma frequency range. Hilar interneurons including the FSINs are known to show membrane potential oscillations phase-locked with the extracellularly recorded oscillations. However, the consequent response of a FSIN to repetitive excitatory gamma synaptic bursts presented either in isolation or in association with membrane potential modulations has not received attention. We show that the FSINs of the DG sub field express a robust long lasting decrease in intrinsic excitability after experiencing bursts of synaptic stimulation of the mossy fiber pathway at gamma frequency (30 Hz), repeated at delta (2 Hz) or theta frequency (4 Hz). Interestingly, the GCs did not express any plasticity of intrinsic excitability upon experiencing similar gamma bursts repeated at delta frequency. The change in intrinsic excitability in the FSINs was observed to be strongly dependent on the somatic current supplement that altered the membrane potential in phase with the synaptic gamma bursts. The plasticity was found to be dependent on the post synaptic calcium flux through the calcium-permeable AMPA receptors (CP-AMPARs) and also on post synaptic HCN channel conductance. Further, decreased excitability in the FSINs exhibited decreased inhibition in the post-synaptic putative granule cells. Additionally, we have used network simulations to predict that the spiking rate of an excitatory neuron is strongly dependent on the intrinsic excitability of a perisomatic targeting interneuron; both integrated in a feedback microcircuit. Given the importance of FSINs in network synchronization, understanding how intrinsic excitability and its plasticity in the FSINs can affect the network attributes is of seminal interest in the field of neuronal circuit dynamics and plasticity. We used computational simulation of physiologically scaled down neuronal networks consisting of experimentally constrained models of neurons to address this question. Intrinsic excitability in FSINs has been experimentally observed to be altered due to changes in their input resistance and changes in their action potential threshold. To alter the input resistance of the FSINs, we changed the specific membrane resistance (Rm), while to change the action potential threshold we altered the peak delayed potassium conductance (gKDbar) In Wang-Buzsaki type FSIN-FSIN interconnected network models (II network) we observed an increase in the network frequency with increase in FSIN Rm while the network coherence did not change due to the altered FSIN Rm. However, in the same network there was a drastic decrease in both network coherence and network frequency with increase in gKDbar. Next, we built an EI network using 250 model excitatory neurons (ENs) and 50 model FSINs. The ENs were reciprocally connected to the FSINs. Moreover, the FSINs were also interconnected among themselves while the ENs were not. In these EI networks we observed that decreased FSIN Rm, which decreased their excitability, caused a monotonic increase in the excitatory network coherence. However, increased FSIN gKDbar which also decreased their excitability caused a decrease in the excitatory network coherence. The excitatory network frequency was decreased with decreased FSIN Rm or with increased FSIN gKDbar. However, EI networks having decreased FSIN input resistance (~ 50 MΩ) could partially rescue the excitatory network coherence from the desynchronizing effect of increased FSIN gKDbar. In EI networks having higher FSIN input resistance (~ 110 MΩ); even a small increase in FSIN gKDbar caused a drastic decrease in the excitatory network coherence. The phenomenon of altered EI network activity due to altered FSIN Rm or FSIN gKDbar was observed to be significantly independent of the proportion of the FSIN population undergoing the alterations. The observation that even a small proportion of the entire FSIN population (10% and 40%; for FSIN Rm dependence and FSIN gKDbar dependence respectively) can cause a massive shift in the EI network activity indicated the strong influence of FSIN intrinsic excitability on network dynamics. We also observed that the dependence of FSIN Rm on EI network activity was quite robust in the physiological range of the network synaptic parameters. Overall from these studies we observed that DG FSINs express activity dependent plasticity of intrinsic excitability after experiencing near physiological synaptic excitation. Further, altered intrinsic excitability of FSINs can cause robust changes in the connected network. The study suggests possible intrinsic strategies in FSINs which might be functional in neuronal microcircuits during different physiological and pathological conditions.
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Ho, Ernest Chun Yue. "If you Want to be Slow you have to be Fast: Control of Slow Population Activities by Fast-spiking Interneurons via Network Multistability." Thesis, 2011. http://hdl.handle.net/1807/30056.

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Slow population activities (SPAs) are population activities in the brain with frequencies of less than 5 Hz. SPAs are prominent in many brain structures including the neocortex and the hippocampus. Examples of SPAs include the neocortical EEG δ waves and the hippocampal large amplitude irregular activities during NREM sleep. These in vivo SPAs are believed to play a fundamental role in brain plasticity. However, despite many experimental attempts to understand SPAs, their mechanisms are still not well understood. It is unclear how the individual neurons can sustain low frequency activities on the network as a whole. In this thesis, we demonstrate that a mathematical and computational perspective is indispensable in understanding slow population phenomena and generating testable hypotheses for future experiments. Our focus is on a hippocampal slice preparation exhibiting spontaneous, inhibitory-based SPAs (hippocampal SPAs). We develop a multi-pronged approach consisting of parameter extraction, simulation, and mathematical analysis to elucidate the mechanisms responsible for hippocampal SPAs. Our results suggest that hippocampal SPAs are an emergent phenomenon. In other words, the network “slowness” is not directly represented by any particular individual element within the network. Instead, the low frequency activities on the network are the result of interactions between synaptic and intrinsic characteristics of individual inhibitory interneurons. Our simulations quantify these characteristics which underlie hippocampal SPAs. Specifically, our simulations predict that individual interneurons should 1) be moderately fast-spiking above threshold before the increase in spike frequency slows down with increasing drive, and 2) be well connected with one another for SPAs to occur. We also predict that excitatory noise levels have a larger influence on hippocampal SPAs than mean excitatory drive. Subsequent mathematical analyses show that the synaptic and intrinsic conditions of individual interneurons as predicted by simulations promote network multi-stability. Hippocampal SPAs occur when the network switches from one network firing state to another. Since many of the parameters we use for simulations are extracted from experiments, our simulation model is likely a reasonable representation of actual biological mechanisms in hippocampal networks.
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Cheng, Ruey-Kuang. "Neural Coding Strategies in Cortico-Striatal Circuits Subserving Interval Timing." Diss., 2010. http://hdl.handle.net/10161/2380.

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Interval timing, defined as timing and time perception in the seconds-to-minutes range, is a higher-order cognitive function that has been shown to be critically dependent upon cortico-striatal circuits in the brain. However, our understanding of how different neuronal subtypes within these circuits cooperate to subserve interval timing remains elusive. The present study was designed to investigate this issue by focusing on the spike waveforms of neurons and their synchronous firing patterns with local field potentials (LFPs) recorded from cortico-striatal circuits while rats were performing two standard interval-timing tasks. Experiment 1 demonstrated that neurons in cortico-striatal circuits can be classified into 4 different clusters based on their distinct spike waveforms and behavioral correlates. These distinct neuronal populations were shown to be differentially involved in timing and reward processing. More importantly, the LFP-spike synchrony data suggested that neurons in 1 particular cluster were putative fast-spiking interneurons (FSIs) in the striatum and these neurons responded to both timing and reward processing. Experiment 2 reported electrophysiological data that were similar with previous findings, but identified a different cluster of striatal neurons - putative tonically-active neurons (TANs), revealed by their distinct spike waveforms and special firing patterns during the acquisition of the task. These firing patterns of FSIs and TANs were in contrast with potential striatal medium-spiny neurons (MSNs) that preferentially responded to temporal processing in the current study. Experiment 3 further investigated the proposal that interval timing is subserved by cortico-striatal circuits by using microstimulation. The findings revealed a stimulation frequency-dependent "stop" or "reset" response pattern in rats receiving microstimulation in either the cortex or the striatum during the performance of the timing task. Taken together, the current findings further support that interval timing is represented in cortico-striatal networks that involve multiple types of interneurons (e.g., FSIs and TANs) functionally connected with the principal projection neurons (i.e., MSNs) in the dorsal striatum. When specific components of these complex networks are electrically stimulated, the ongoing timing processes are temporarily "stopped" or "reset" depending on the properties of the stimulation.


Dissertation
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Частини книг з теми "Fast Spiking Interneurons (FSINs)"

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Fish, Kenneth N., Guillermo Gonzalez-Burgos, Aleksey V. Zaitsev, and David A. Lewis. "Histological Characterization of Physiologically Determined Fast-Spiking Interneurons in Slices of Primate Dorsolateral Prefrontal Cortex." In Isolated Central Nervous System Circuits, 159–81. Totowa, NJ: Humana Press, 2012. http://dx.doi.org/10.1007/978-1-62703-020-5_4.

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2

Zeberg, Hugo, Nathan W. Gouwens, Kunichika Tsumoto, Takashi Tateno, Kazuyuki Aihara, and Hugh P. C. Robinson. "Phase-Resetting Analysis of Gamma-Frequency Synchronization of Cortical Fast-Spiking Interneurons Using Synaptic-like Conductance Injection." In Phase Response Curves in Neuroscience, 489–509. New York, NY: Springer New York, 2011. http://dx.doi.org/10.1007/978-1-4614-0739-3_20.

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Behrens, M. Margarita. "Studying Schizophrenia in a Dish: Use of Primary Neuronal Cultures to Study the Long-Term Effects of NMDA Receptor Antagonists on Parvalbumin-Positive Fast-Spiking Interneurons." In Animal Models of Schizophrenia and Related Disorders, 127–48. Totowa, NJ: Humana Press, 2011. http://dx.doi.org/10.1007/978-1-61779-157-4_6.

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4

Chesselet, Marie-Françoise, Joshua L. Plotkin, Nanping Wu, and Michael S. Levine. "Development of striatal fast-spiking GABAergic interneurons." In Progress in Brain Research, 261–72. Elsevier, 2007. http://dx.doi.org/10.1016/s0079-6123(06)60015-0.

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5

Fasching, Liana, Melanie Brady, and Flora M. Vaccarino. "Cellular and Molecular Pathology in Tourette Syndrome." In Tourette Syndrome, edited by Liana Fasching, Melanie Brady, and Flora M. Vaccarino, 171–83. 2nd ed. Oxford University Press, 2022. http://dx.doi.org/10.1093/med/9780197543214.003.0012.

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Abstract This chapter summarizes the available literature and data on pathological findings in Tourette syndrome. In severe, unremitting Tourette syndrome, there are decreases in somatostatin-positive/nitric oxide synthase–positive interneurons, fast spiking parvalbumin-positive/γ-aminobutyric acid-ergic interneurons, as well as tonically active cholinergic interneurons in the caudate nucleus and putamen. There is also a prominent increase in inflammation throughout the basal ganglia along with activation of microglial cells. Overall, neuroimaging studies suggest that the basal ganglia, a set of nuclei situated deep within the cerebral cortical hemispheres, are a central component of the pathophysiology of TS. These findings are discussed in light of current views on the pathogenic mechanisms underlying tic disorders.
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Merchant, Hugo, and Apostolos P. Georgopoulos. "Inhibitory Mechanisms in the Motor Cortical Circuit." In Handbook of Brain Microcircuits, edited by Gordon M. Shepherd and Sten Grillner, 67–74. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190636111.003.0006.

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Inhibitory mechanisms are crucial for the integrated operation of the motor cortical circuit. Local inhibition is exerted by interneurons that are GABAergic, nonpyramidal cells with short, nonprojecting axons. Interneurons can be classified into at least two groups: fast-spiking (FS) neurons and instrinsic bursting (IB) neurons. In the primary motor cortex, FS cells may sculpe the tuning dispersion of directionally selective putative pyramidal cells during reaching in behaving monkeys. Analysis of putative interneuronal activity also allowed to discard the role of inhibition as a gating mechanism in motor control. The development of high-density, semichronic electrode systems for extracellular recordings in behaving primates will allow a closer investigation of the role of interneuronal inhibition in directional tuning and voluntary motor control. The results discussed in this chapter agree with the authors’ proposal that local inhibitory mechanisms may be intimately involved in controlling the directional accuracy and speed of the reaching movement.
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