Phospholipase C beta 1 in the dentate gyrus gates fear memory formation through regulation of neuronal excitability

Abstract

Memory processes rely on a molecular signaling system that balances the interplay between positive and negative modulators. Recent research has focused on identifying memory-regulating genes and their mechanisms. Phospholipase C beta 1 (PLCβ1), highly expressed in the hippocampus, reportedly serves as a convergence point for signal transduction through G protein-coupled receptors. However, the detailed role of PLCβ1 in memory function has not been elucidated. Here, we demonstrate that PLCβ1 in the dentate gyrus functions as a memory suppressor. We reveal that mice lacking PLCβ1 in the dentate gyrus exhibit a heightened fear response and impaired memory extinction, and this excessive fear response is repressed by upregulation of PLCβ1 through its overexpression or activation using a newly developed optogenetic system. Last, our results demonstrate that PLCβ1 overexpression partially inhibits exaggerated fear response caused by traumatic experience. Together, PLCβ1 is crucial in regulating contextual fear memory formation and potentially enhancing the resilience to trauma-related conditions.