Activity-dependent gene regulations in PV+ interneurons
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ABSTRACT:
PROVIDER: PRJNA924748 | ENA |
REPOSITORIES: ENA
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Project description:Neuronal activity is regulated in a narrow permissive band for the proper operation of biological neural networks. Changes in synaptic connectivities and network processes during key cognitive activity such as learning might disturb this balance, eliciting compensatory mechanisms to maintain network function1–3. In the neocortex, excitatory pyramidal cells and inhibitory interneurons exhibit robust forms of stabilising plasticity. However, while neuronal plasticity has been thoroughly studied in pyramidal cells4–8, comparatively little is known about how interneurons adapt to ongoing changes in their activity. Here we uncover critical cellular and molecular mechanisms underlying homeostatic regulation of parvalbumin-expressing (PV+) interneurons activity in mouse neocortex. We found that changes in the activity of PV+ interneurons drive cell-autonomous, bi-directional compensatory adjustments of the number and strength of inhibitory synapses received by these cells, specifically from other PV+ interneurons. High-throughput profiling of ribosome-associated mRNAs revealed that increasing the activity of PV+ interneurons leads to the cell-autonomous upregulation of Vgf, a gene encoding multiple neuropeptides. Functional experiments conclusively point towards the role VGF in mediating activity-dependent scaling of inhibitory synapses in PV+ interneurons. Our findings reveal an instructive role for VGF in regulating the connectivity among PV+ interneurons in the adult neocortex.
2025-01-28 | GSE223038 | GEO
Project description:CUT&RUN for MEF2C in mature PV+ and SST+ cortical interneurons to characterize the differential usage of this transcription factor by these populations.
2021-09-22 | GSE165018 | 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:Gamma-aminobutyric acid-containing (GABAergic) interneurons are the major source of inhibition in the mammalian brain. They control the output of principal neurons, shaping brain oscillations and maintaining excitation/inhibition balance. PV+ interneurons play a major role in the regulation of the excitatory/inhibitory balance in the cortex. One gene of the oxidative phosphorylation machinery shows particularly specific expression in PV+ interneurons, Cox6a2. The gene codes for the isoform 2 of the subunit Cox6a in cytochrome c oxidase, also known as complex IV (CIV), of oxidative phosphorylation. Cox6a2 had been shown to regulate the generation of energy in the heart and skeletal muscle to meet the high energy demands. To unravel the molecular signaling that contributes to the increase in oxidative stress and metabolic dysregulation following Cox6a2 knockout, we sorted PV+ interneurons from wild-type and Cox6a2-/- mice using the PV-EGFP transgenic mouse line and compared the neuronal transcriptome between the two phenotypes by RNA sequencing. We noted significant transcriptional changes in Cox6a2-/- PV+ interneurons relative to WT. Thus, we found deregulated expression of a number of genes that are involved in synaptic transmission and cellular metabolism.
2020-01-01 | E-MTAB-7879 | biostudies-arrayexpress
Project description:One of the earliest pathophysiological perturbations in Alzheimer’s Disease (AD) may arise from dysfunction of fast-spiking parvalbumin (PV) interneurons (PV-INs). Defining early protein-level (proteomic) alterations in PV-INs can provide key biological and translationally relevant insights. Here, we use cell-type-specific in vivo biotinylation of proteins (CIBOP) coupled with mass spectrometry to obtain native-state proteomes of PV interneurons. PV-INs exhibited proteomic signatures of high metabolic, mitochondrial, and translational activity, with over-representation of causally linked AD genetic risk factors. Analyses of bulk brain proteomes indicated strong correlations between PV-IN proteins with cognitive decline in humans, and with progressive neuropathology in humans and mouse models of Aβ pathology. Furthermore, PV-IN-specific proteomes revealed unique signatures of increased mitochondrial and metabolic proteins, but decreased synaptic and mTOR signaling proteins in response to early Aβ pathology. PV-specific changes were not apparent in whole-brain proteomes. These findings showcase the first nativestate PV-IN proteomes in mammalian brain, revealing a molecular basis for their unique vulnerabilities in AD
2024-03-04 | PXD043963 | Pride
Project description:The emerging role of epigenetic mechanisms like DNA methylation executed by DNA methyltransferases (DNMTs) in synaptic function irrevocably raises the question for the targeted subcellular processes and mechanisms. We here sequenced FAC-sorted PVergic interneurons of 6 month and 18month old PV-Cre/tdTomato/Dnmt1loxp wildtype and knockout mice and performed RNA-Seq and MeDIP-Seq.
2020-07-06 | GSE145026 | GEO
Project description:The emerging role of epigenetic mechanisms like DNA methylation executed by DNA methyltransferases (DNMTs) in synaptic function irrevocably raises the question for the targeted subcellular processes and mechanisms. We here sequenced FAC-sorted PVergic interneurons of 6 month and 18month old PV-Cre/tdTomato/Dnmt1loxp wildtype and knockout mice and performed RNA-Seq.
2020-07-06 | GSE145025 | GEO
Project description:The emerging role of epigenetic mechanisms like DNA methylation executed by DNA methyltransferases (DNMTs) in synaptic function irrevocably raises the question for the targeted subcellular processes and mechanisms. We here sequenced FAC-sorted PVergic interneurons of 6 month and 18month old PV-Cre/tdTomato/Dnmt1loxp wildtype and knockout mice and performed MeDIP-Seq.
2020-07-06 | GSE145024 | GEO
Project description:Nova proteins direct synaptic integration of somatostatin interneurons through activity- dependent alternative splicing
| PRJNA600006 | 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