Electrical synapses between inhibitory neurons shape the responses of principal neurons to transient inputs in the thalamus

AbstractAs multimodal sensory information proceeds to the cortex, it is intercepted and processed by the nuclei of the thalamus. The main source of inhibition within thalamus is the reticular nucleus (TRN), which collects signals both from thalamocortical relay neurons and from thalamocortical feedback. Within the reticular nucleus, neurons are densely interconnected by connexin36-based gap junctions, known as electrical synapses. Electrical synapses have been shown to coordinate neuronal rhythms, including thalamocortical spindle rhythms, but their role in shaping or modulating transient activity is less understood. We constructed a four-cell model of thalamic relay and TRN neurons, and used it to investigate the impact of electrical synapses on closely timed inputs delivered to thalamic relay cells. We show that the electrical synapses of the TRN assist cortical discrimination of these inputs through effects of truncation, delay or inhibition of thalamic spike trains. We expect that these are principles whereby electrical synapses play similar roles in processing of transient activity in excitatory neurons across the brain.

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Asymmetry and modulation of spike timing in electrically coupled neurons

Journal of Neurophysiology ◽

10.1152/jn.00843.2014 ◽

2015 ◽

Vol 113 (6) ◽

pp. 1743-1751 ◽

Cited By ~ 10

Author(s):

Jessica Sevetson ◽

Julie S. Haas

Keyword(s):

Critical Role ◽

Electrical Coupling ◽

Brain Slices ◽

Spike Timing ◽

Thalamic Reticular Nucleus ◽

Reticular Nucleus ◽

Electrical Synapses ◽

Thalamic Relay ◽

Coupled Networks ◽

The Brain

Electrical coupling mediates interactions between neurons of the thalamic reticular nucleus (TRN), which play a critical role in regulating thalamocortical and corticothalamic communication by inhibiting thalamic relay cells. Accumulating evidence has shown that asymmetry of electrical synapses is a fundamental and dynamic property, but the effect of asymmetry on coupled networks is unexplored. Recording from patched pairs in rat brain slices, we investigate asymmetry in the subthreshold regime and show that electrical synapses can exert powerful effects on the spike times of coupled neighbors. Electrical synaptic signaling modulates spike timing by 10–20 ms, in an effect that also exhibits asymmetry. Furthermore, we show through modeling that coupling asymmetry expands the set of outputs for pairs of coupled neurons through enhanced regions of synchrony and reversals of spike order. These results highlight the power and specificity of signaling exerted by electrical synapses, which contribute to information flow across the brain.

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Neuronal Circuits in Barrel Cortex for Whisker Sensory Perception

Physiological Reviews ◽

10.1152/physrev.00019.2019 ◽

2021 ◽

Vol 101 (1) ◽

pp. 353-415

Author(s):

Jochen F. Staiger ◽

Carl C. H. Petersen

Keyword(s):

Barrel Cortex ◽

Specific Activity ◽

Sensory Information ◽

Inhibitory Neurons ◽

Future Research ◽

Cell Type ◽

Molecular Features ◽

Somatotopic Map ◽

Cell Type Specific ◽

The Impact

The array of whiskers on the snout provides rodents with tactile sensory information relating to the size, shape and texture of objects in their immediate environment. Rodents can use their whiskers to detect stimuli, distinguish textures, locate objects and navigate. Important aspects of whisker sensation are thought to result from neuronal computations in the whisker somatosensory cortex (wS1). Each whisker is individually represented in the somatotopic map of wS1 by an anatomical unit named a ‘barrel’ (hence also called barrel cortex). This allows precise investigation of sensory processing in the context of a well-defined map. Here, we first review the signaling pathways from the whiskers to wS1, and then discuss current understanding of the various types of excitatory and inhibitory neurons present within wS1. Different classes of cells can be defined according to anatomical, electrophysiological and molecular features. The synaptic connectivity of neurons within local wS1 microcircuits, as well as their long-range interactions and the impact of neuromodulators, are beginning to be understood. Recent technological progress has allowed cell-type-specific connectivity to be related to cell-type-specific activity during whisker-related behaviors. An important goal for future research is to obtain a causal and mechanistic understanding of how selected aspects of tactile sensory information are processed by specific types of neurons in the synaptically connected neuronal networks of wS1 and signaled to downstream brain areas, thus contributing to sensory-guided decision-making.

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Two dynamically distinct circuits driving inhibition in sensory thalamus

10.1101/2020.04.16.044487 ◽

2020 ◽

Author(s):

Rosa I. Martinez-Garcia ◽

Bettina Voelcker ◽

Julia B. Zaltsman ◽

Saundra L. Patrick ◽

Tanya R. Stevens ◽

...

Keyword(s):

Sensory Information ◽

Cell Types ◽

Higher Order ◽

Inhibitory Neurons ◽

Thalamic Reticular Nucleus ◽

Reticular Nucleus ◽

Order Structure ◽

Multiple Sources ◽

Cell Groups ◽

And Function

AbstractMost sensory information destined for the neocortex is relayed through the thalamus, where considerable transformation occurs1,2. One powerful means of transformation involves interactions between excitatory thalamocortical neurons that carry data to cortex and inhibitory neurons of the thalamic reticular nucleus (TRN) that regulate flow of those data3-6. Despite enduring recognition of its importance7-9, understanding of TRN cell types, their organization, and their functional properties has lagged that of the thalamocortical systems they control.Here we address this, investigating somatosensory and visual circuits of the TRN. In the somatosensory TRN we observed two groups of genetically defined neurons that are topographically segregated, physiologically distinct, and connect reciprocally with independent thalamocortical nuclei via dynamically divergent synapses. Calbindin-expressing cells, located in the central core, connect with the ventral posterior nucleus (VP), the primary somatosensory thalamocortical relay. In contrast, somatostatin-expressing cells, residing along the surrounding edges of TRN, synapse with the posterior medial thalamic nucleus (POM), a higher-order structure that carries both top-down and bottom-up information10-12. The two TRN cell groups process their inputs in pathway-specific ways. Synapses from VP to central TRN cells transmit rapid excitatory currents that depress deeply during repetitive activity, driving phasic spike output. Synapses from POM to edge TRN cells evoke slower, less depressing excitatory currents that drive more persistent spiking. Differences in intrinsic physiology of TRN cell types, including state-dependent bursting, contribute to these output dynamics. Thus, processing specializations of two somatosensory TRN subcircuits appear to be tuned to the signals they carry—a primary central subcircuit to discrete sensory events, and a higher-order edge subcircuit to temporally distributed signals integrated from multiple sources. The structure and function of visual TRN subcircuits closely resemble those of the somatosensory TRN. These results provide fundamental insights about how subnetworks of TRN neurons may differentially process distinct classes of thalamic information.

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Losing Dnmt3a dependent methylation in inhibitory neurons impairs neural function by a mechanism impacting Rett syndrome

eLife ◽

10.7554/elife.52981 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 8

Author(s):

Laura A Lavery ◽

Kerstin Ure ◽

Ying-Wooi Wan ◽

Chongyuan Luo ◽

Alexander J Trostle ◽

...

Keyword(s):

Rett Syndrome ◽

Strong Dependence ◽

Neurological Dysfunction ◽

Inhibitory Neurons ◽

Neural Function ◽

Transcriptional Alterations ◽

Epigenetic Gene Regulation ◽

Distinct Features ◽

The Impact ◽

The Brain

Methylated cytosine is an effector of epigenetic gene regulation. In the brain, Dnmt3a is the sole ‘writer’ of atypical non-CpG methylation (mCH), and MeCP2 is the only known ‘reader’ for mCH. We asked if MeCP2 is the sole reader for Dnmt3a dependent methylation by comparing mice lacking either protein in GABAergic inhibitory neurons. Loss of either protein causes overlapping and distinct features from the behavioral to molecular level. Loss of Dnmt3a causes global loss of mCH and a subset of mCG sites resulting in more widespread transcriptional alterations and severe neurological dysfunction than MeCP2 loss. These data suggest that MeCP2 is responsible for reading only part of the Dnmt3a dependent methylation in the brain. Importantly, the impact of MeCP2 on genes differentially expressed in both models shows a strong dependence on mCH, but not Dnmt3a dependent mCG, consistent with mCH playing a central role in the pathogenesis of Rett Syndrome.

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Thalamocortical spectral transmission relies on balanced input strengths

10.1101/2020.09.20.305136 ◽

2020 ◽

Author(s):

Matteo Saponati ◽

Jordi Garcia-Ojalvo ◽

Enrico Cataldo ◽

Alberto Mazzoni

Keyword(s):

Sensory Information ◽

Field Potential ◽

Sensory Cortex ◽

Inhibitory Neurons ◽

Spectral Transmission ◽

Sensory Transmission ◽

Thalamocortical Connections ◽

Primary Sensory Cortex ◽

Spiking Network ◽

The Brain

AbstractThe thalamus is a key element of sensory transmission in the brain, as all sensory information is processed by the thalamus before reaching the cortex. The thalamus is known to gate and select sensory streams through a modulation of its internal activity in which spindle oscillations play a preponderant role, but the mechanism underlying this process is not completely understood. In particular, how do thalamocortical connections convey stimulus-driven information selectively over the background of thalamic internally generated activity (such as spindle oscillations)? Here we investigate this issue with a spiking network model of connectivity between thalamus and primary sensory cortex reproducing the local field potential of both areas. We found two features of the thalamocortical dynamics that filter out spindle oscillations: i) spindle oscillations are weaker in neurons projecting to the cortex, ii) the resonance dynamics of cortical networks selectively blocks frequency in the range encompassing spindle oscillations. This latter mechanism depends on the balance of the strength of thalamocortical connections toward excitatory and inhibitory neurons in the cortex. Our results pave the way toward an integrated understanding of the sensory streams traveling between the periphery and the cortex.

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GABABR Modulation of Electrical Synapses and Plasticity in the Thalamic Reticular Nucleus

International Journal of Molecular Sciences ◽

10.3390/ijms222212138 ◽

2021 ◽

Vol 22 (22) ◽

pp. 12138

Author(s):

Huaixing Wang ◽

Julie S. Haas

Keyword(s):

Signaling Pathways ◽

Neuronal Activity ◽

Gabab Receptor ◽

Receptor Activation ◽

Gabab Receptors ◽

Electrical Synapse ◽

Thalamic Reticular Nucleus ◽

Reticular Nucleus ◽

Electrical Synapses ◽

The Impact

Two distinct types of neuronal activity result in long-term depression (LTD) of electrical synapses, with overlapping biochemical intracellular signaling pathways that link activity to synaptic strength, in electrically coupled neurons of the thalamic reticular nucleus (TRN). Because components of both signaling pathways can also be modulated by GABAB receptor activity, here we examined the impact of GABAB receptor activation on the two established inductors of LTD in electrical synapses. Recording from patched pairs of coupled rat neurons in vitro, we show that GABAB receptor inactivation itself induces a modest depression of electrical synapses and occludes LTD induction by either paired bursting or metabotropic glutamate receptor (mGluR) activation. GABAB activation also occludes LTD from either paired bursting or mGluR activation. Together, these results indicate that afferent sources of GABA, such as those from the forebrain or substantia nigra to the reticular nucleus, gate the induction of LTD from either neuronal activity or afferent glutamatergic receptor activation. These results add to a growing body of evidence that the regulation of thalamocortical transmission and sensory attention by TRN is modulated and controlled by other brain regions. Significance: We show that electrical synapse plasticity is gated by GABAB receptors in the thalamic reticular nucleus. This effect is a novel way for afferent GABAergic input from the basal ganglia to modulate thalamocortical relay and is a possible mediator of intra-TRN inhibitory effects.

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Modulation of tactile feedback for the execution of dexterous movement

10.1101/2021.03.04.433649 ◽

2021 ◽

Author(s):

James M Conner ◽

Andrew Bohannon ◽

Masakazu Igarashi ◽

James Taniguchi ◽

Nicholas Baltar ◽

...

Keyword(s):

Cortical Neurons ◽

Molecular Genetic ◽

Sensory Information ◽

Tactile Feedback ◽

Inhibitory Neurons ◽

Tactile Information ◽

Inhibitory Circuits ◽

Complementary Pattern ◽

Local Circuits ◽

The Brain

While dexterity relies on the constant transmission of sensory information, unchecked feedback can be disruptive to behavior. Yet how somatosensory feedback from the hands is regulated as it first enters the brain, and whether this modulation exerts any influence on movement, remain unclear. Leveraging molecular-genetic access in mice, we find that tactile afferents from the hand recruit neurons in the brainstem cuneate nucleus whose activity is modulated by distinct classes of local inhibitory neurons. Selective manipulation of these inhibitory circuits can suppress or enhance the transmission of tactile information, affecting behaviors that rely on movement of the hands. Investigating whether these local circuits are subject to top-down control, we identify distinct descending cortical pathways that innervate cuneate in a complementary pattern. Somatosensory cortical neurons target the core tactile region of cuneate, while a large rostral cortical population drives feed-forward inhibition of tactile transmission through an inhibitory shell. These findings identify a circuit basis for tactile feedback modulation, enabling the effective execution of dexterous movement.

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A circuit motif in the zebrafish hindbrain for a two alternative behavioral choice to turn left or right

eLife ◽

10.7554/elife.16808 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 31

Author(s):

Minoru Koyama ◽

Francesca Minale ◽

Jennifer Shum ◽

Nozomi Nishimura ◽

Chris B Schaffer ◽

...

Keyword(s):

Escape Behavior ◽

Network Motif ◽

Sensory Information ◽

Network Connectivity ◽

Inhibitory Neurons ◽

Behavioral Studies ◽

Behavioral Choices ◽

The Right ◽

The Brain

Animals collect sensory information from the world and make adaptive choices about how to respond to it. Here, we reveal a network motif in the brain for one of the most fundamental behavioral choices made by bilaterally symmetric animals: whether to respond to a sensory stimulus by moving to the left or to the right. We define network connectivity in the hindbrain important for the lateralized escape behavior of zebrafish and then test the role of neurons by using laser ablations and behavioral studies. Key inhibitory neurons in the circuit lie in a column of morphologically similar cells that is one of a series of such columns that form a developmental and functional ground plan for building hindbrain networks. Repetition within the columns of the network motif we defined may therefore lie at the foundation of other lateralized behavioral choices.

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Relation Between Level of Prefrontal Activity and Subject's Performance

Journal of Psychophysiology ◽

10.1027//0269-8803.13.2.117 ◽

1999 ◽

Vol 13 (2) ◽

pp. 117-125 ◽

Cited By ~ 14

Author(s):

Laurence Casini ◽

Françoise Macar ◽

Marie-Hélène Giard

Keyword(s):

Brain Activity ◽

Sensory Information ◽

Practice Phase ◽

Trained Subjects ◽

Anagram Task ◽

Economic Information ◽

Long Duration ◽

Level Of Activity ◽

The Brain ◽

Processing Mechanism

Abstract The experiment reported here was aimed at determining whether the level of brain activity can be related to performance in trained subjects. Two tasks were compared: a temporal and a linguistic task. An array of four letters appeared on a screen. In the temporal task, subjects had to decide whether the letters remained on the screen for a short or a long duration as learned in a practice phase. In the linguistic task, they had to determine whether the four letters could form a word or not (anagram task). These tasks allowed us to compare the level of brain activity obtained in correct and incorrect responses. The current density measures recorded over prefrontal areas showed a relationship between the performance and the level of activity in the temporal task only. The level of activity obtained with correct responses was lower than that obtained with incorrect responses. This suggests that a good temporal performance could be the result of an efficacious, but economic, information-processing mechanism in the brain. In addition, the absence of this relation in the anagram task results in the question of whether this relation is specific to the processing of sensory information only.

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Measuring the World

10.1093/oso/9780198779636.003.0017 ◽

2018 ◽

Author(s):

Ann-Sophie Barwich

Keyword(s):

Sensory Information ◽

Network Models ◽

Model System ◽

Stimulus Input ◽

Expectancy Effects ◽

Neural Network Models ◽

Perceptual Object ◽

External Objects ◽

The Common ◽

The Brain

How much does stimulus input shape perception? The common-sense view is that our perceptions are representations of objects and their features and that the stimulus structures the perceptual object. The problem for this view concerns perceptual biases as responsible for distortions and the subjectivity of perceptual experience. These biases are increasingly studied as constitutive factors of brain processes in recent neuroscience. In neural network models the brain is said to cope with the plethora of sensory information by predicting stimulus regularities on the basis of previous experiences. Drawing on this development, this chapter analyses perceptions as processes. Looking at olfaction as a model system, it argues for the need to abandon a stimulus-centred perspective, where smells are thought of as stable percepts, computationally linked to external objects such as odorous molecules. Perception here is presented as a measure of changing signal ratios in an environment informed by expectancy effects from top-down processes.

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