Kim, Hye Yun Yang, Yong Ryoul Hwang, Hongik Lee, Ha-Eun Jang, Hyun-Jun Kim, Jeongyeon Yang, Esther Kim, Hyun Rhim, Hyewhon Suh, Pann-Ghill Kim, Jae-Ick 2024-01-19T19:01:35Z 2024-01-19T19:01:35Z 2021-09-04 2019-11 2045-2322 https://pubs.kist.re.kr/handle/201004/119411 Synaptic inhibition plays a fundamental role in the information processing of neural circuits. It sculpts excitatory signals and prevents hyperexcitability of neurons. Owing to these essential functions, dysregulated synaptic inhibition causes a plethora of neurological disorders, including epilepsy, autism, and schizophrenia. Among these disorders, epilepsy is associated with abnormal hyperexcitability of neurons caused by the deficits of GABAergic neuron or decreased GABAergic inhibition at synapses. Although many antiepileptic drugs are intended to improve GABA-mediated inhibition, the molecular mechanisms of synaptic inhibition regulated by GABAergic neurons are not fully understood. Increasing evidence indicates that phospholipase C gamma 1 (PLC gamma 1) is involved in the generation of seizure, while the causal relationship between PLC gamma 1 and seizure has not been firmly established yet. Here, we show that genetic deletion of PLC gamma 1 in GABAergic neurons leads to handling-induced seizure in aged mice. In addition, aged Plcg1(F/F); Dlx5/6-Cre mice exhibit other behavioral alterations, including hypoactivity, reduced anxiety, and fear memory deficit. Notably, inhibitory synaptic transmission as well as the number of inhibitory synapses are decreased in the subregions of hippocampus. These findings suggest that PLC gamma 1 may be a key determinant of maintaining both inhibitory synapses and synaptic transmission, potentially contributing to the regulation of E/I balance in the hippocampus. English Nature Publishing Group Deletion of PLC gamma 1 in GABAergic neurons increases seizure susceptibility in aged mice Article 10.1038/s41598-019-54477-4 1 Scientific Reports, v.9 Scientific Reports 9 Y scie scopus 000499678000001 2-s2.0-85075652032 Multidisciplinary Sciences Science & Technology - Other Topics Article DYSFUNCTION MESSENGER-RNA EXPRESSION POSITIVE INTERNEURONS RAT FOREBRAIN FEAR MEMORY EPILEPSY BDNF BRAIN TRKB IMMUNOREACTIVITY