The role of TRPV4 in acute sleep deprivation-induced fear memory impairment

Abstract

Acute sleep deprivation (ASD) negatively impacts fear memory, but the underlying mechanisms are not fully understood. Transient receptor potential vanilloid 4 (TRPV4), a cation channel which is closely correlated with the concentration of Ca2+, and neuronal Ca2+ overloading is a crucial inducement of learning and memory impairment. This study utilized an acute sleep-deprived mouse model combined with fear conditioning to investigate these mechanisms. mRNA sequencing revealed increased expression of TRPV4 in mice with ASD-induced fear memory impairment. Notably, knockdown of TRPV4 reversed ASD-induced fear memory impairment. ASD leads to the increased concentration of Ca2+. Additionally, we observed a reduction in spine density and a significant decrease in postsynaptic density protein 95 (PSD95), which is associated with synaptic plasticity, in sleep-deprived fear memory impairment mice. This indicates that ASD may cause overloaded Ca2+, disrupting synaptic plasticity and impairing fear memory. Moreover, TRPV4 knockdown significantly decreased Ca2+ concentration, mitigated the loss of dendritic spines and reduction of PSD95, contributing to the restoration of fear memory. These findings indicate a potential protective role of TRPV4 knockdown in counteracting ASD-induced fear memory deficits. Collectively, our results highlight that TRPV4 may be a potential therapeutic target in mediating fear memory impairment due to ASD and underscore the importance of sleep management for conditions like PTSD.