Complementary networks of cortical somatostatin interneurons enforce layer specific control
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PROVIDER: PRJNA644462 | ENA |
REPOSITORIES: ENA
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Project description:The neocortex is functionally organized into layers. Layer four receives the densest bottom up sensory inputs, while layers 2/3 and 5 receive top down inputs that may convey predictive information. A subset of cortical somatostatin (SST) neurons, the Martinotti cells, gate top down input by inhibiting the apical dendrites of pyramidal cells in layers 2/3 and 5, but it is unknown whether an analogous inhibitory mechanism controls activity in layer 4. Using high precision circuit mapping, in vivo optogenetic perturbations, and single cell transcriptional profiling, we reveal complementary circuits in the mouse barrel cortex involving genetically distinct SST subtypes that specifically and reciprocally interconnect with excitatory cells in different layers: Martinotti cells connect with layers 2/3 and 5, whereas non-Martinotti cells connect with layer 4. By enforcing layer-specific inhibition, these parallel SST subnetworks could independently regulate the balance between bottom up and top down input.
2020-07-07 | GSE153824 | GEO
Project description:The neocortex is functionally organized into layers. Layer four receives the densest bottom up sensory inputs, while layers 2/3 and 5 receive top down inputs that may convey predictive information. A subset of cortical somatostatin (SST) neurons, the Martinotti cells, gate top down input by inhibiting the apical dendrites of pyramidal cells in layers 2/3 and 5, but it is unknown whether an analogous inhibitory mechanism controls activity in layer 4. Using high precision circuit mapping, in vivo optogenetic perturbations, and single cell transcriptional profiling, we reveal complementary circuits in the mouse barrel cortex involving genetically distinct SST subtypes that specifically and reciprocally interconnect with excitatory cells in different layers: Martinotti cells connect with layers 2/3 and 5, whereas non-Martinotti cells connect with layer 4. By enforcing layer-specific inhibition, these parallel SST subnetworks could independently regulate the balance between bottom up and top down input.
| S-EPMC6422636 | biostudies-literature
Project description:Total RNA-sequencing of FACs isolated nucleus accumbens somatostatin interneuron nuclei Somatostatin interneuron loss in multiple cortical brain regions has been observed postmortem in humans with several neuropsychiatric disorders and their loss is proposed to underlie some common pathological changes in circuit function across numerous syndromes. However, somatostatin interneurons in the nucleus accumbens (NAc), a key brain reward region, remain poorly understood due to the fact that these cells account for <1% of NAc neurons. Here, we used Flouresence activated cell sorting to isolate nuclei of somatostatin-expressing interneurons in the Nucleus Accumbens from individual SST-TLG498 reporter mice that express membrane bound EGFP-F specifically in somatostatin-expressing neurons. We then performed cell-type specific Total RNA-sequencing to characterize the entire transcriptome of NAc somatostatin interneurons after repeated exposure (7 days) to either saline or cocaine. We identified a wide variety of coding and non-coding transcripts that were expressed at high levels and were differentially expressed between saline and cocaine treated mice. Repeated cocaine administration induces transcriptome-wide changes in gene expression within NAc somatostatin interneurons, with particular regulation of transcripts related to neural plasticity. Our results identify alterations in NAc induced by cocaine in a sparse population of somatostatin interneurons, and illustrate the value of studying brain diseases using cell type-specific whole transcriptome RNA-sequencing to identify novel neurpathophysiology.
2018-07-03 | GSE116484 | GEO
Project description:Somatostatin interneurons are the earliest born population of inhibitory cells. They are crucial to support normal brain development and function; however, the mechanisms underlying their integration into nascent cortical circuitry are not well understood. In this study, we begin by demonstrating that the maturation of somatostatin interneurons is activity dependent. We then investigated the relationship between activity, alternative splicing and synapse formation within this population. Specifically, we discovered that the Nova family of RNA-binding proteins are activity-dependent and are essential for the maturation of somatostatin interneurons, as well as their afferent and efferent connectivity. Moreover, in somatostatin interneurons, Nova2 preferentially mediates the alternative splicing of genes required for axonal formation and synaptic function. Hence, our work demonstrates that the Nova family of proteins are centrally involved in coupling developmental neuronal activity to cortical circuit formation.
2023-06-20 | GSE143316 | GEO
Project description:The mammalian cerebral cortex contains an extraordinary diversity of cell types that emerge through the implementation of different developmental programs. Delineating when and how cellular diversification occurs is particularly challenging for cortical inhibitory neurons, as they represent a relatively small proportion of all cortical cells, migrate tangentially from their embryonic origin to the cerebral cortex, and have a protracted development. Here we combine single-cell RNA sequencing and spatial transcriptomics to characterize the emergence of neuronal diversity among somatostatin-expressing (SST+) cells, the most diverse subclass of inhibitory neurons in the mouse cerebral cortex. We found that SST+ inhibitory neurons segregate during embryonic stages into long-range projection (LRP) neurons and two types of interneurons, Martinotti cells and non-Martinotti cells, following distinct developmental trajectories. Two main subtypes of LRP neurons and several subtypes of interneurons are readily distinguishable in the embryo, although interneuron diversity is further refined during early postanal life. Our results suggest that the timing for cellular diversification is unique for different subtypes of SST+ neurons and particularly divergent for LRP neurons and interneurons. Thus, the diversification of SST+ inhibitory neurons involves a temporal cascade of unique molecular programs driving their divergent developmental trajectories.
2023-11-01 | GSE217065 | GEO
Project description:ARNT2 Controls Prefrontal Somatostatin Interneurons Mediating Affective Empathy
| PRJNA1042633 | ENA
Project description:People with schizophrenia show hyperactivity in the ventral hippocampus (vHipp) and we have previously demonstrated distinct behavioral roles for vHipp cell populations. Here, we test the hypothesis that parvalbumin (PV) and somatostatin (SST) interneurons differentially innervate and regulate hippocampal pyramidal neurons based on their projection target. First, we use eGRASP to show that PV-positive interneurons form a similar number of synaptic connections with pyramidal cells regardless of their projection target while SST-positive interneurons preferentially target nucleus accumbens (NAc) projections. To determine if these anatomical differences result in functional changes, we used in vivo opto-electrophysiology to show that SST cells also preferentially regulate the activity of NAc-projecting cells. These results suggest vHipp interneurons differentially regulate that vHipp neurons that project to the medial prefrontal cortex (mPFC) and NAc. Characterization of these cell populations may provide potential molecular targets for the treatment schizophrenia and other psychiatric disorders associated with vHipp dysfunction.
2023-11-09 | GSE244159 | GEO
Project description:Cortical interneurons display a remarkable diversity in their morphology, physiological properties and connectivity. Elucidating the molecular determinants underlying this heterogeneity is essential for understanding interneuron development and function. We discovered that alternative splicing differentially regulates the integration of somatostatin- and parvalbumin-expressing interneurons into nascent cortical circuits through the cell-type specific tailoring of mRNAs. Specifically, we identified a role for the activity-dependent splicing regulator Rbfox1 in the development of cortical interneuron subtype specific efferent connectivity. Our work demonstrates that Rbfox1 mediates largely non-overlapping alternative splicing programs within two distinct but related classes of interneurons.
2018-10-12 | GSE119998 | GEO
Project description:Discrete hippocampal projections are differentially regulated by parvalbumin and somatostatin interneurons
| PRJNA1021548 | ENA
Project description:Transcriptional alterations in Nucleus Accumbens somatostatin interneurons following exposure to cocaine
| PRJNA478793 | ENA