{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Selten M"],"funding":["European Research Council"],"pagination":["173-181"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12222018"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["643(8070)"],"pubmed_abstract":["Neuronal activity must be regulated in a narrow permissive band for the proper operation of neural networks. Changes in synaptic connectivity and network activity-for example, during 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 stabilizing plasticity. However, although neuronal plasticity has been thoroughly studied in pyramidal cells4-8, little is known about how interneurons adapt to persistent changes in their activity. Here we describe a critical cellular process through which cortical parvalbumin-expressing (PV+) interneurons adapt to changes in their activity levels. We found that changes in the activity of individual PV+ interneurons drive bidirectional 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 mRNA revealed that increasing the activity of a PV+ interneuron leads to upregulation of two genes encoding multiple secreted neuropeptides: Vgf and Scg2. Functional experiments demonstrated that VGF is critically required for the activity-dependent scaling of inhibitory PV+ synapses onto PV+ interneurons. Our findings reveal an instructive role for neuropeptide-encoding genes in regulating synaptic connections among PV+ interneurons in the adult mouse neocortex."],"journal":["Nature"],"pubmed_title":["Regulation of PV interneuron plasticity by neuropeptide-encoding genes."],"pmcid":["PMC12222018"],"funding_grant_id":["787355"],"pubmed_authors":["Oozeer F","Hamid F","Selten M","Bernard C","Zimmer C","Hanusz-Godoy A","Mukherjee D","Marin O"],"additional_accession":[]},"is_claimable":false,"name":"Regulation of PV interneuron plasticity by neuropeptide-encoding genes.","description":"Neuronal activity must be regulated in a narrow permissive band for the proper operation of neural networks. Changes in synaptic connectivity and network activity-for example, during 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 stabilizing plasticity. However, although neuronal plasticity has been thoroughly studied in pyramidal cells4-8, little is known about how interneurons adapt to persistent changes in their activity. Here we describe a critical cellular process through which cortical parvalbumin-expressing (PV+) interneurons adapt to changes in their activity levels. We found that changes in the activity of individual PV+ interneurons drive bidirectional 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 mRNA revealed that increasing the activity of a PV+ interneuron leads to upregulation of two genes encoding multiple secreted neuropeptides: Vgf and Scg2. Functional experiments demonstrated that VGF is critically required for the activity-dependent scaling of inhibitory PV+ synapses onto PV+ interneurons. Our findings reveal an instructive role for neuropeptide-encoding genes in regulating synaptic connections among PV+ interneurons in the adult mouse neocortex.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Jul","modification":"2026-06-02T06:01:12.439Z","creation":"2026-04-15T03:10:02.143Z"},"accession":"S-EPMC12222018","cross_references":{"pubmed":["40307547"],"doi":["10.1038/s41586-025-08933-z"]}}