Contribution of Interneuron Subtype-Specific GABAergic Signaling to Emergent Sensory Processing in Mouse Somatosensory Whisker Barrel Cortex

Abstract Mammalian neocortex is important for conscious processing of sensory information with balanced glutamatergic and GABAergic signaling fundamental to this function. Yet little is known about how this interaction arises despite increasing insight into early GABAergic interneuron (IN) circuits. To study this, we assessed the contribution of specific INs to the development of sensory processing in the mouse whisker barrel cortex, specifically the role of INs in early speed coding and sensory adaptation. In wild-type animals, both speed processing and adaptation were present as early as the layer 4 critical period of plasticity and showed refinement over the period leading to active whisking onset. To test the contribution of IN subtypes, we conditionally silenced action-potential-dependent GABA release in either somatostatin (SST) or vasoactive intestinal peptide (VIP) INs. These genetic manipulations influenced both spontaneous and sensory-evoked cortical activity in an age- and layer-dependent manner. Silencing SST + INs reduced early spontaneous activity and abolished facilitation in sensory adaptation observed in control pups. In contrast, VIP + IN silencing had an effect towards the onset of active whisking. Silencing either IN subtype had no effect on speed coding. Our results show that these IN subtypes contribute to early sensory processing over the first few postnatal weeks.

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Contribution of interneuron subtype-specific GABAergic signalling to emergent sensory processing in somatosensory whisker barrel cortex in mouse

10.1101/2021.02.18.431791 ◽

2021 ◽

Author(s):

Liad J. Baruchin ◽

Michael M. Kohl ◽

Simon J.B Butt

Keyword(s):

Sensory Processing ◽

Barrel Cortex ◽

Sensory Information ◽

Gaba Release ◽

Gabaergic Interneuron ◽

Dependent Manner ◽

Sensory Adaptation ◽

Layer 4 ◽

Evoked Activity ◽

Sensory Evoked

AbstractMammalian neocortex is important for conscious processing of sensory information. Fundamental to this function is balanced glutamatergic and GABAergic signalling. Yet little is known about how this interaction arises in the developing forebrain despite increasing insight into early GABAergic interneuron (IN) circuits. To further study this, we assessed the contribution of specific INs to the development of sensory processing in the mouse whisker barrel cortex. Specifically we explored the role of INs in speed coding and sensory adaptation. In wild-type animals, both speed processing and adaptation were present as early as the layer 4 critical period of plasticity, and showed refinement over the period leading to active whisking onset. We then conditionally silenced action-potential-dependent GABA release in either somatostatin (SST) or vasoactive intestinal peptide (VIP) INs. These genetic manipulations influenced both spontaneous and sensory-evoked activity in an age and layer-dependent manner. Silencing SST+ INs reduced early spontaneous activity and abolished facilitation in sensory adaptation observed in control pups. In contrast, VIP+ IN silencing had an effect towards the onset of active whisking. Silencing either IN subtype had no effect on speed coding. Our results reveal how these IN subtypes differentially contribute to early sensory processing over the first few postnatal weeks.

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Loss of Calretinin in L5a impairs the formation of the barrel cortex leading to abnormal whisker-mediated behaviors

Molecular Brain ◽

10.1186/s13041-021-00775-w ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Mingzhao Su ◽

Junhua Liu ◽

Baocong Yu ◽

Kaixing Zhou ◽

Congli Sun ◽

...

Keyword(s):

Information Integration ◽

Pyramidal Neurons ◽

Barrel Cortex ◽

Sensory Information ◽

Membrane Excitability ◽

Novelty Preference ◽

Layer 4 ◽

Dendritic Complexity ◽

Cortex System

AbstractThe rodent whisker-barrel cortex system has been established as an ideal model for studying sensory information integration. The barrel cortex consists of barrel and septa columns that receive information input from the lemniscal and paralemniscal pathways, respectively. Layer 5a is involved in both barrel and septa circuits and play a key role in information integration. However, the role of layer 5a in the development of the barrel cortex remains unclear. Previously, we found that calretinin is dynamically expressed in layer 5a. In this study, we analyzed calretinin KO mice and found that the dendritic complexity and length of layer 5a pyramidal neurons were significantly decreased after calretinin ablation. The membrane excitability and excitatory synaptic transmission of layer 5a neurons were increased. Consequently, the organization of the barrels was impaired. Moreover, layer 4 spiny stellate cells were not able to properly gather, leading to abnormal formation of barrel walls as the ratio of barrel/septum size obviously decreased. Calretinin KO mice exhibited deficits in exploratory and whisker-associated tactile behaviors as well as social novelty preference. Our study expands our knowledge of layer 5a pyramidal neurons in the formation of barrel walls and deepens the understanding of the development of the whisker-barrel cortex system.

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Pathway-, layer- and cell-type-specific thalamic input to mouse barrel cortex

eLife ◽

10.7554/elife.52665 ◽

2019 ◽

Vol 8 ◽

Cited By ~ 13

Author(s):

B Semihcan Sermet ◽

Pavel Truschow ◽

Michael Feyerabend ◽

Johannes M Mayrhofer ◽

Tess B Oram ◽

...

Keyword(s):

Thalamic Nucleus ◽

Barrel Cortex ◽

Sensory Information ◽

Cell Types ◽

Excitatory Input ◽

Higher Order ◽

Inhibitory Neurons ◽

Thalamic Nuclei ◽

Thalamic Input ◽

Layer 4

Mouse primary somatosensory barrel cortex (wS1) processes whisker sensory information, receiving input from two distinct thalamic nuclei. The first-order ventral posterior medial (VPM) somatosensory thalamic nucleus most densely innervates layer 4 (L4) barrels, whereas the higher-order posterior thalamic nucleus (medial part, POm) most densely innervates L1 and L5A. We optogenetically stimulated VPM or POm axons, and recorded evoked excitatory postsynaptic potentials (EPSPs) in different cell-types across cortical layers in wS1. We found that excitatory neurons and parvalbumin-expressing inhibitory neurons received the largest EPSPs, dominated by VPM input to L4 and POm input to L5A. In contrast, somatostatin-expressing inhibitory neurons received very little input from either pathway in any layer. Vasoactive intestinal peptide-expressing inhibitory neurons received an intermediate level of excitatory input with less apparent layer-specificity. Our data help understand how wS1 neocortical microcircuits might process and integrate sensory and higher-order inputs.

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Cellular and Synaptic Phenotype Compensations Limit Circuit Disruption in Fmr1-KO Mouse Layer 4 Barrel Cortex but Fail to Prevent Deficits in Information Processing

10.1101/403725 ◽

2018 ◽

Author(s):

Aleksander P.F. Domanski ◽

Sam A. Booker ◽

David J.A. Wyllie ◽

John T.R. Isaac ◽

Peter C. Kind

Keyword(s):

Sensory Processing ◽

Knockout Mice ◽

Barrel Cortex ◽

Fragile X ◽

Neuronal Function ◽

Sensory Hypersensitivity ◽

Layer 4 ◽

Network Simulations ◽

Sensory Encoding ◽

Critical Process

AbstractSensory hypersensitivity is a common and debilitating feature of neurodevelopmental disorders such as Fragile X Syndrome (FXS). However, how developmental changes in neuronal function ultimately culminate in the network dysfunction that underlies sensory hypersensitivities is not known. To address this, we studied the layer 4 barrel cortex circuit in Fmr1 knockout mice, a critical sensory processing circuit in this mouse model of FXS. By systematically studying cellular and synaptic properties of layer 4 neurons and combining with cellular and network simulations, we explored how the array of phenotypes in Fmr1 knockout produce circuit pathology during development that result in sensory processing dysfunction. We show that many of the cellular and synaptic pathologies in Fmr1 knockout mice are antagonistic, mitigating circuit dysfunction, and hence can be regarded as compensatory to the primary pathology. Despite this compensation, the layer 4 network in the Fmr1 knockout exhibits significant alterations in spike output in response to ascending thalamocortical input that we show results in impaired sensory encoding. We suggest that it is this developmental loss of layer 4 sensory encoding precision that drives subsequent developmental alterations in layer 4 – layer 2/3 connectivity and plasticity observed in the Fmr1 knockout, and is a critical process producing sensory hypersensitivity.

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Neocortex Network Activation and Deactivation States Controlled by the Thalamus

Journal of Neurophysiology ◽

10.1152/jn.00955.2009 ◽

2010 ◽

Vol 103 (3) ◽

pp. 1147-1157 ◽

Cited By ~ 63

Author(s):

Akio Hirata ◽

Manuel A. Castro-Alamancos

Keyword(s):

Brain Stem ◽

Sensory Processing ◽

Basal Forebrain ◽

Barrel Cortex ◽

Sensory Information ◽

Network Activity ◽

Tonic Firing ◽

Network Activation ◽

Activated State

Neocortex network activity varies from a desynchronized or activated state typical of arousal to a synchronized or deactivated state typical of quiescence. Such changes are usually attributed to the effects of neuromodulators released in the neocortex by nonspecific activating systems originating in basal forebrain and brain stem reticular formation. As a result, the only role attributed to thalamocortical cells projecting to primary sensory areas, such as barrel cortex, is to transmit sensory information. However, thalamocortical cells can undergo significant changes in spontaneous tonic firing as a function of state, although the role of such variations is unknown. Here we show that the tonic firing level of thalamocortical cells, produced by cholinergic and noradrenergic stimulation of the somatosensory thalamus in urethane-anesthetized rats, controls neocortex activation and deactivation. Thus in addition to its well-known role in the relay of sensory information, the thalamus can control the state of neocortex activation, which may complement the established roles in this regard of basal forebrain and brain stem nuclei. Because of the topographical organization of primary thalamocortical pathways, this mechanism provides a means by which area-specific neocortical activation can occur, which may be useful for modality-specific sensory processing or selective attention.

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Local and thalamic origins of ongoing and sensory evoked cortical correlations

10.1101/058727 ◽

2016 ◽

Cited By ~ 1

Author(s):

Katayun Cohen-Kashi Malina ◽

Boaz Mohar ◽

Akiva N. Rappaport ◽

Miao Liu

Keyword(s):

Barrel Cortex ◽

Field Potential ◽

Sensory Response ◽

Cortical Cells ◽

Synaptic Inputs ◽

Correlated Activity ◽

Layer 4 ◽

Lower Variability ◽

Intact Cortex ◽

Sensory Evoked

Thalamic inputs of layer 4 (L4) cells in sensory cortices are outnumbered by local connections. Thus, it was suggested that robust sensory response in L4 emerges due to synchronized thalamic activity. In order to investigate the role of both inputs in generation of cortical synchronization, we isolated the thalamic excitatory inputs of cortical cells by optogenetically silencing cortical firing. In anesthetized mice, we measured the correlation between isolated thalamic synaptic inputs of simultaneously patched nearby L4 cells of the barrel cortex. In contrast to correlated activity of excitatory synaptic inputs in the intact cortex, isolated thalamic inputs exhibit lower variability and asynchronous spontaneous and sensory evoked inputs. These results were further supported in awake mice when we recorded the excitatory inputs of individual cortical cells simultaneously with the local field potential (LFP) in a nearby site. Our results therefore indicate that cortical synchronization emerges by intracortical coupling.

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Deep Cortical Layers Are Activated Directly by Thalamus

Science ◽

10.1126/science.1236425 ◽

2013 ◽

Vol 340 (6140) ◽

pp. 1591-1594 ◽

Cited By ~ 242

Author(s):

Christine M. Constantinople ◽

Randy M. Bruno

Keyword(s):

Synaptic Input ◽

Sensory Information ◽

Evoked Responses ◽

Cortical Column ◽

Cortical Layers ◽

Thalamic Neurons ◽

Main Route ◽

Layer 4 ◽

Sensory Evoked

The thalamocortical (TC) projection to layer 4 (L4) is thought to be the main route by which sensory organs communicate with cortex. Sensory information is believed to then propagate through the cortical column along the L4→L2/3→L5/6 pathway. Here, we show that sensory-evoked responses of L5/6 neurons in rats derive instead from direct TC synapses. Many L5/6 neurons exhibited sensory-evoked postsynaptic potentials with the same latencies as L4. Paired in vivo recordings from L5/6 neurons and thalamic neurons revealed substantial convergence of direct TC synapses onto diverse types of infragranular neurons, particularly in L5B. Pharmacological inactivation of L4 had no effect on sensory-evoked synaptic input to L5/6 neurons. L4 is thus not an obligatory distribution hub for cortical activity, and thalamus activates two separate, independent “strata” of cortex in parallel.

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Projection-specific Activity of Layer 2/3 Neurons Imaged in Mouse Primary Somatosensory Barrel Cortex During a Whisker Detection Task

Function ◽

10.1093/function/zqaa008 ◽

2020 ◽

Vol 1 (1) ◽

Cited By ~ 2

Author(s):

Angeliki Vavladeli ◽

Tanya Daigle ◽

Hongkui Zeng ◽

Sylvain Crochet ◽

Carl C H Petersen

Keyword(s):

Motor Cortex ◽

Task Performance ◽

Somatosensory Cortex ◽

Barrel Cortex ◽

Specific Activity ◽

Sensory Information ◽

Dependent Manner ◽

Sensory Stimuli ◽

Sensorimotor Transformations ◽

Longitudinal Imaging

Abstract The brain processes sensory information in a context- and learning-dependent manner for adaptive behavior. Through reward-based learning, relevant sensory stimuli can become linked to execution of specific actions associated with positive outcomes. The neuronal circuits involved in such goal-directed sensory-to-motor transformations remain to be precisely determined. Studying simple learned sensorimotor transformations in head-restrained mice offers the opportunity for detailed measurements of cellular activity during task performance. Here, we trained mice to lick a reward spout in response to a whisker deflection and an auditory tone. Through two-photon calcium imaging of retrogradely labeled neurons, we found that neurons located in primary whisker somatosensory barrel cortex projecting to secondary whisker somatosensory cortex had larger calcium signals than neighboring neurons projecting to primary whisker motor cortex in response to whisker deflection and auditory stimulation, as well as before spontaneous licking. Longitudinal imaging of the same neurons revealed that these projection-specific responses were relatively stable across 3 days. In addition, the activity of neurons projecting to secondary whisker somatosensory cortex was more highly correlated than for neurons projecting to primary whisker motor cortex. The large and correlated activity of neurons projecting to secondary whisker somatosensory cortex might enhance the pathway-specific signaling of important sensory information contributing to task execution. Our data support the hypothesis that communication between primary and secondary somatosensory cortex might be an early critical step in whisker sensory perception. More generally, our data suggest the importance of investigating projection-specific neuronal activity in distinct populations of intermingled excitatory neocortical neurons during task performance.

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Layer 1 NDNF+ Interneurons Control Bilateral Sensory Processing in a Layer-dependent Manner

10.1101/2021.12.02.470902 ◽

2021 ◽

Author(s):

Rasmus Vighagen ◽

Lorenzo Gesuita ◽

Angeliki Damilou ◽

Anna Cavaccini ◽

Lila Banterle ◽

...

Keyword(s):

Sensory Processing ◽

Cortical Neurons ◽

Essential Role ◽

Sensory Information ◽

Dependent Manner ◽

Regulatory Pathway ◽

Ipsilateral Side ◽

The World ◽

Layer 2 ◽

Contralateral Cortex

ABSTRACTBilateral sensory information is indispensable for navigating the world. In most mammals, signals sensed by either side of the midline will ultimately reach the cortex where they will be integrated for perception and appropriate action selection. Even though information transferred across the hemispheres is routed through the corpus callosum, how and which microcircuits are key in integrating it is not well understood. Here we identify an essential role for layer 1 NDNF+ inhibitory cells of mice in integrating bilateral whisker-evoked information in an NMDA receptor-dependent manner. Direct connections from the contralateral cortex and the ipsilateral side activate NDNF+ neurons, which subsequently inhibit the late spiking activity of underlying layer 2/3 neurons, but not layer 5. Our results identify a feed-forward regulatory pathway for bilateral cortical sensory processing of upper layer cortical neurons actuated via layer 1 NDNF+ interneurons.

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Thalamus drives two complementary input strata of the neocortex in parallel

10.1101/524298 ◽

2019 ◽

Author(s):

R. Egger ◽

R.T. Narayanan ◽

D. Udvary ◽

A. Bast ◽

J.M. Guest ◽

...

Keyword(s):

Cortical Area ◽

Sensory Information ◽

Evoked Responses ◽

Cortical Processing ◽

Thalamocortical Axons ◽

Starting Point ◽

Input Layer ◽

Layer 4 ◽

Sensory Evoked ◽

Parallel Activation

Sensory information enters the neocortex via thalamocortical axons that define the major ‘input’ layer 4. The same thalamocortical axons, however, additionally innervate the deep ‘output’ layers 5/6. How such bistratification impacts cortical processing remains unknown. Here, we find a class of neurons that cluster specifically around thalamocortical axons at the layer 5/6 border. We show that these border stratum cells are characterized by extensive horizontal axons, that they receive strong convergent input from the thalamus, and that this input is sufficient to drive reliable sensory-evoked responses, which precede those in layer 4. These cells are hence strategically placed to amplify and relay thalamocortical inputs across the cortical area, for example to drive the fast onsets of cortical output patterns. Layer 4 is therefore not the sole starting point of cortical processing. Instead, parallel activation of layer 4 and the border stratum is necessary to broadcast information out of the neocortex.

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