Deletion of PLCγ1 in GABAergic neurons increases seizure susceptibility in aged mice

Hye Yun Kim, Yong Ryoul Yang, Hongik Hwang, Ha Eun Lee, Hyun Jun Jang, Jeongyeon Kim, Esther Yang, Hyun Kim, Hyewhon Rhim, Pann Ghill Suh, Jae Ick Kim

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Abstract

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.

Original languageEnglish
Article number17761
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 2019 Dec 1

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    Kim, H. Y., Yang, Y. R., Hwang, H., Lee, H. E., Jang, H. J., Kim, J., Yang, E., Kim, H., Rhim, H., Suh, P. G., & Kim, J. I. (2019). Deletion of PLCγ1 in GABAergic neurons increases seizure susceptibility in aged mice. Scientific reports, 9(1), [17761]. https://doi.org/10.1038/s41598-019-54477-4