Transcriptomics

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Activity-dependent gene regulations in PV+ interneurons


ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE223038 | GEO | 2025/01/28

REPOSITORIES: GEO

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