| First Author | Kim HY | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 17761 |
| PubMed ID | 31780806 | Mgi Jnum | J:287177 |
| Mgi Id | MGI:6405977 | Doi | 10.1038/s41598-019-54477-4 |
| Citation | Kim HY, et al. (2019) Deletion of PLCgamma1 in GABAergic neurons increases seizure susceptibility in aged mice. Sci Rep 9(1):17761 |
| abstractText | 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 Cgamma1 (PLCgamma1) is involved in the generation of seizure, while the causal relationship between PLCgamma1 and seizure has not been firmly established yet. Here, we show that genetic deletion of PLCgamma1 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 PLCgamma1 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. |
