TY - JOUR
T1 - Deletion of PLCγ1 in GABAergic neurons increases seizure susceptibility in aged mice
AU - Kim, Hye Yun
AU - Yang, Yong Ryoul
AU - Hwang, Hongik
AU - Lee, Ha Eun
AU - Jang, Hyun Jun
AU - Kim, Jeongyeon
AU - Yang, Esther
AU - Kim, Hyun
AU - Rhim, Hyewhon
AU - Suh, Pann Ghill
AU - Kim, Jae Ick
N1 - Funding Information:
We thank Yun-Ji Choi, Soo-Ah Park, Soo-Hyeon Hwang for providing technical support and materials for animal experiments. We thank Seung Eun Lee and Jea Kwon for instructing EEG recording. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (2017R1E1A1A01074510 to P.-G.S., 2017R1C1B3005476 to J.-I.K.), the POSCO Science Fellowship of POSCO TJ Park Foundation (J.-I.K.), Research Fund (1.170060.01, 1.180070.01) of Ulsan National Institute of Science and Technology (J.-I.K.). This research was also supported by Korea Brain Research Institute (KBRI) basic research program through KBRI funded by the Ministry of Science and ICT (19-BR-03-02 to J.K.).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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 Cγ1 (PLCγ1) is involved in the generation of seizure, while the causal relationship between PLCγ1 and seizure has not been firmly established yet. Here, we show that genetic deletion of PLCγ1 in GABAergic neurons leads to handling-induced seizure in aged mice. In addition, aged Plcg1F/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 PLCγ1 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.
AB - 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 Cγ1 (PLCγ1) is involved in the generation of seizure, while the causal relationship between PLCγ1 and seizure has not been firmly established yet. Here, we show that genetic deletion of PLCγ1 in GABAergic neurons leads to handling-induced seizure in aged mice. In addition, aged Plcg1F/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 PLCγ1 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.
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U2 - 10.1038/s41598-019-54477-4
DO - 10.1038/s41598-019-54477-4
M3 - Article
C2 - 31780806
AN - SCOPUS:85075652032
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 17761
ER -