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 (PLC beta 1), highly expressed in the hippocampus, reportedly serves as a convergence point for signal transduction through G protein-coupled receptors. However, the detailed role of PLC beta 1 in memory function has not been elucidated. Here, we demonstrate that PLC beta 1 in the dentate gyrus functions as a memory suppressor. We reveal that mice lacking PLC beta 1 in the dentate gyrus exhibit a heightened fear response and impaired memory extinction, and this excessive fear response is repressed by upregulation of PLC beta 1 through its overexpression or activation using a newly developed optogenetic system. Last, our results demonstrate that PLC beta 1 overexpression partially inhibits exaggerated fear response caused by traumatic experience. Together, PLC beta 1 is crucial in regulating contextual fear memory formation and potentially enhancing the resilience to trauma-related conditions.