Elucidating the memory function of phospholipase C beta 1 in the hippocampus using an optogenetic system

Abstract

Memory processes rely on molecular signaling system that carefully balances the interplay between positive and negative modulators. Accordingly, recent research has focused on identifying the memory regulator genes and their mechanisms. Phospholipase C beta 1 ($PLC \beta 1$) is an initial enzyme for signaling delivery from environmental information to subcellular organelles by producing second messengers, IP3 and DAG, inducing $Ca^{2+}$ signaling or recruiting protein kinase C family, respectively. The $PLC \beta 1$ serves as a convergent point for signal transduction through G protein-coupled receptors, receiving signals from neurotransmitters, and is highly expressed in the hippocampus. However, the role of $PLC \beta 1$ in memory function has not been confirmed yet. Here, we demonstrate that $PLC \beta 1$ functions as a memory suppressor in the dentate gyrus. We found that mice lacking $PLC \beta 1$ in the dentate gyrus exhibit an heightened fear response and slower memory extinction. Conversely, the upregulation of $PLC \beta 1$ through overexpression and activation using a newly developed optogenetic system represses excessive fear response. furthermore, our results show that $PLC \beta 1$ constraints exaggerated fear response caused by traumatic experience, suggesting that $PLC \beta 1$ plays a crucial role in regulating the fear memory encoding, potentially enhancing resilience to trauma-related conditions.