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    Functional thalamocortical innervation of VIP- and SST-expressing GABAergic interneurons in mouse barrel cortex

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    http://dx.doi.org/10.13039/501100001659 German Research FoundationOpen-Access-Publikationsfonds 202

    Distribution Patterns of Three Molecularly Defined Classes of GABAergic Neurons Across Columnar Compartments in Mouse Barrel Cortex

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    The mouse somatosensory cortex is an excellent model to study the structural basis of cortical information processing, since it possesses anatomically recognizable domains that receive different thalamic inputs, which indicates spatial segregation of different processing tasks. In this work we examined three genetically labeled, non-overlapping subpopulations of GABAergic neurons: parvalbumin- (PV+), somatostatin- (SST+), and vasoactive intestinal polypeptide-expressing (VIP+) cells. Each of these subpopulations displayed a unique cellular distribution pattern across layers. In terms of columnar localization, the distribution of these three populations was not quantitatively different between barrel-related versus septal compartments in most layers. However, in layer IV (LIV), SST+, and VIP+, but not PV+ neurons preferred the septal compartment over barrels. The examined cell types showed a tendency toward differential distribution in supragranular and infragranular barrel-related versus septal compartments, too. Our data suggests that the location of GABAergic neuron cell bodies correlates with the spatial pattern of cortical domains receiving different kinds of thalamic input. Thus, at least in LIV, lemniscal inputs present a close spatial relation preferentially to PV+ cells whereas paralemniscal inputs target compartments in which more SST+ and VIP+ cells are localized. Our findings suggest pathway-specific roles for neocortical GABAergic neurons

    Characterizing VIP Neurons in the Barrel Cortex of VIPcre/tdTomato Mice Reveals Layer-Specific Differences

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    Neocortical GABAergic interneurons have a profound impact on cortical circuitry and its information processing capacity. Distinct subgroups of inhibitory interneurons can be distinguished by molecular markers, such as parvalbumin, somatostatin, and vasoactive intestinal polypeptide (VIP). Among these, VIP-expressing interneurons sparked a substantial interest since these neurons seem to operate disinhibitory circuit motifs found in all major neocortical areas. Several of these recent studies used transgenic Vip-ires-cre mice to specifically target the population of VIP-expressing interneurons. This makes it necessary to elucidate in detail the sensitivity and specificity of Cre expression for VIP neurons in these animals. Thus, we quantitatively compared endogenous tdTomato with Vip fluorescence in situ hybridization and alpha VIP immunohistochemistry in the barrel cortex of VIPcre/tdTomato mice in a layer-specific manner. We show that VIPcre/tdTomato mice are highly sensitive and specific for the entire population of VIP-expressing neurons. In the barrel cortex, approximately 13% of all GABAergic neurons are VIP expressing. Most VIP neurons are found in layer II/III (similar to 60%), whereas approximately 40% are found in the other layers of the barrel cortex. Layer II/III VIP neurons are significantly different from VIP neurons in layers IV-VI in several morphological and membrane properties, which suggest layer-dependent differences in functionality

    VIP-to-SST cell circuit motif shows differential short-term plasticity across sensory areas of mouse cortex

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    Inhibition of GABAergic interneurons has been found to critically fine-tune the excitation-inhibition balance of the cortex. Inhibition is mediated by many connectivity motifs formed by GABAergic neurons. One such motif is the inhibition of somatostatin (SST)-expressing neurons by vasoactive intestinal polypeptide (VIP)-expressing neurons. We studied the synaptic properties of layer (L) 2/3 VIP cells onto L4 SST cells in somatosensory (S1) and visual (V1) cortices of mice of either sex using paired whole-cell patch clamp recordings, followed by morphological reconstructions. We identified strong differences in the morphological features of L4 SST cells, wherein cells in S1 fell into the non-Martinotti cell (nMC) subclass, while in V1 presented with Martinotti cell (MC)-like features. Around 40-45% of tested SST cells were inhibited by VIP cells in both cortices. While unitary connectivity properties of the VIP-to-nMC and VIP-to-MC motif were comparable, we observed stark differences in short-term plasticity. During high-frequency stimulation of both motifs, some connections showed short-term facilitation while others showed a stable response, with a fraction of VIP-to-nMC connections showing short-term depression. We thus provide evidence that VIP cells target morphological subclasses of SST cells differentially, forming cell-type specific inhibitory motifs. Significance statement Inhibitory circuits are involved in a wide variety of cortical computations. In particular, the inhibition of somatostatin-expressing (SST) neurons by vasoactive intestinal polypeptide- expressing (VIP) neurons has been well-documented in L2/3 of sensory cortices. It was recently identified that L4 SST neurons of S1 and V1 exhibit two different morphological subtypes, namely, non-Martinotti (nMC) cells in S1 and Martinotti (MC) cells in V1. We show that L2/3 VIP neurons inhibit both SST subtypes in L4 with similar dynamics. However, we also find that under high frequency stimulations, the VIP-to-nMC motif exhibits strong short-term depression, but this was not observed in VIP-to-MC motifs. Therefore, we identified morphologically distinct, inhibitory cell-type specific motifs in sensory cortices of mouse

    Inhibitory circuit motifs of cortical somatosensory layer 5 SST interneurons are uniform within layers but specific across layers

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    Abstract Layer (L) 5 is a hub in the cortical column in which a multitude of feedforward and feedback pathways converge. These inputs are then transmitted to distant sites by resident pyramidal neurons (PN). L5 PN are under the strong influence of local somatostatin (SST)‐expressing interneurons (IN). To better understand the inhibitory control of L5 SST cells, which leads to disinhibition of excitatory cells, we used paired whole‐cell patch‐clamp recordings in acute brain slices. We investigated whether they receive intra‐ and translaminar inputs by parvalbumin (PV) and vasoactive intestinal polypeptide (VIP) IN and what type of short‐term synaptic plasticity these inputs display. In triple transgenic mice we found that intralaminarly both PV and VIP IN effectively target L5 SST IN. PV to SST connections were depressing at all tested frequencies, whereas VIP to SST connections were facilitating at high‐frequency VIP IN stimulation. In addition translaminar inputs from L2/3 VIP to L5 SST IN showed similar connectivity rates and short‐term plasticity compared to their L5 counterparts. However L2/3 PV IN, despite numerous descending axon collaterals, showed hardly any connection. In summary we are able to show that intralaminar circuit motifs of L5 SST IN resemble those previously studied in L2/3. Furthermore we demonstrate a selective translaminar targeting by L2/3 VIP IN that was missing from PV IN. These results shine new light on the circuit layout that enables intra‐ and translaminar dis/inhibitory processing in the cortical column. image Key points L5 somatostatin (SST)‐expressing interneurons (IN) are widely targeted by other GABAergic IN in their home layer. The origin of this afferent inhibition is from parvalbumin (PV), as well as vasoactive intestinal peptide (VIP)‐expressing GABAergic IN within L5, whereas L2/3 translaminar input originates from VIP but not from PV IN. Many of these connections are formed in a bidirectional manner. PV to SST and VIP to SST connections displayed cell type‐specific differences in unitary synaptic properties and short‐term plasticity. Our results help us to better understand intra‐ and translaminar dis/inhibitory processing, which might optimize tactile information processing in the cortical column.Deutsche Forschungsgemeinschaft https://doi.org/10.13039/50110000165

    Thalamocortical Connections Drive Intracortical Activation of Functional Columns in the Mislaminated Reeler Somatosensory Cortex

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    Neuronal wiring is key to proper neural information processing. Tactile information from the rodent's whiskers reaches the cortex via distinct anatomical pathways. The lemniscal pathway relays whisking and touch information from the ventral posteromedial thalamic nucleus to layer IV of the primary somatosensory "barrel" cortex. The disorganized neocortex of the reeler mouse is a model system that should severely compromise the ingrowth of thalamocortical axons (TCAs) into the cortex. Moreover, it could disrupt intracortical wiring. We found that neuronal intermingling within the reeler barrel cortex substantially exceeded previous descriptions, leading to the loss of layers. However, viral tracing revealed that TCAs still specifically targeted transgenically labeled spiny layer IV neurons. Slice electrophysiology and optogenetics proved that these connections represent functional synapses. In addition, we assessed intracortical activation via immediate-early-gene expression resulting from a behavioral exploration task. The cellular composition of activated neuronal ensembles suggests extensive similarities in intracolumnar information processing in the wild-type and reeler brains. We conclude that extensive ectopic positioning of neuronal partners can be compensated for by cell-autonomous mechanisms that allow for the establishment of proper connectivity. Thus, genetic neuronal fate seems to be of greater importance for correct cortical wiring than radial neuronal position

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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