{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n INSYN1 (Inhibitory Synaptic Protein 1) is emerging as a critical molecular determinant for the proper organization and function of GABAergic synapses. Studies have shown that effective inhibitory synaptic transmission depends on the targeted delivery and stabilization of GABA receptors at postsynaptic sites, and INSYN1 plays an essential role in this process. By interacting with components of the dystroglycan complex (DGC), INSYN1 facilitates the precise localization and clustering of GABA receptors, thereby ensuring the integrity of inhibitory synaptic contacts. In support of this, CRISPR-mediated depletion of INSYN1 has been demonstrated to significantly reduce the number of inhibitory postsynaptic sites and the frequency of miniature inhibitory currents, leading to increased neuronal excitability in the hippocampus."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Furthermore, loss of INSYN1 disrupts the composition of the DGC at inhibitory synapses, correlating with abnormal neuronal network activity and deficits in cognitive functions such as fear conditioning memory."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Collectively, these findings underscore the importance of INSYN1 in targeting and maintaining inhibitory GABAergic function—an essential requirement for establishing excitatory/inhibitory balance in neural circuits—with wide-ranging implications for understanding the molecular basis of neurodevelopmental and cognitive disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Chang-Hoon Cho "}, {"type": "b", "children": [{"type": "t", "text": "Commentary: GARLH Family Proteins Stabilize GABA"}, {"type": "a", "children": [{"type": "t", "text": "sub"}], "href": "sub"}, {"type": "t", "text": "A"}, {"type": "a", "children": [{"type": "t", "text": "/sub"}], "href": "/sub"}, {"type": "t", "text": " Receptors at Synapses."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Mol Neurosci (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fnmol.2017.00169"}], "href": "https://doi.org/10.3389/fnmol.2017.00169"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28611592"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28611592"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Akiyoshi Uezu, Erin Hisey, Yoshihiko Kobayashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Essential role for InSyn1 in dystroglycan complex integrity and cognitive behaviors in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Elife (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.7554/eLife.50712"}], "href": "https://doi.org/10.7554/eLife.50712"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31829939"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31829939"}]}]}]}