{"doi":"10.1101/2022.12.06.519295","title":"Syngap1 Regulates Cortical Circuit Assembly by Controlling Membrane Excitability","abstract":"Summary Gene expression intersects with neural activity to produce cortical circuits during brain development. However, the cell biological mechanisms linking gene expression to activity-dependent cortical circuit assembly remain unclear. Here, we demonstrate in mice that a newly discovered function of the neurodevelopmental disorder gene, Syngap1 , is to cell-autonomously control intrinsic membrane excitability (IME) in developing cortical glutamatergic neurons. Syngap1 regulation of IME was mechanistically linked to wiring of a cortical circuit motif required for sensory processing and behavioral action. Restoring depressed IME in Syngap1 deficient neurons through genetic targeting of hyper-functional potassium currents unleashed deficient dendritic morphogenesis in upper lamina sensory cortex pyramidal neurons. Furthermore, enhancing dendritic morphogenesis was sufficient to stimulate assembly of translaminar feed-forward excitatory circuit motifs. Thus, Syngap1 promotes excitatory circuit assembly during cortical development by maintaining IME in a range that enables trophic neuronal activity to maximize pyramidal cell somatodendritic maturation and subsequent synapse formation. Highlights Syngap1 cell-autonomously tunes cortical pyramidal neuron IME in vivo Syngap1 -IME is regulated in part by control of neuronal potassium currents Syngap1 enhancement of IME drives dendritic maturation in pyramidal cells Syngap1 tuning of IME-regulated dendritic maturation promotes circuit assembly","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":297609,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9506,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":365892,"name":"Sheldon D. Michaelson","orcid":null,"position":1,"is_corresponding":false},{"id":907036,"name":"Massimiliano Aceti","orcid":"0000-0002-6632-1398","position":2,"is_corresponding":false},{"id":986190,"name":"Murat Kilinic","orcid":null,"position":3,"is_corresponding":false},{"id":300768,"name":"Courtney A. Miller","orcid":"0000-0001-8628-4902","position":4,"is_corresponding":false},{"id":296428,"name":"Gavin Rumbaugh","orcid":"0000-0001-6360-3894","position":5,"is_corresponding":false},{"id":300763,"name":"Vineet Arora","orcid":"0000-0001-7856-0401","position":0,"is_corresponding":true}],"reference_count":91,"raw_metadata":null,"created_at":"2026-07-19T00:31:26.161109Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}