Roles of TRPC4 Channels in the Hippocampal CA1 Region in Spatial Working Memory and Contextual Novelty

Abstract

Working memory is the retainability of a small amount of information available for ongoing activities. Transient receptor potential channels (TRPC1–7) may be involved in this process. This study explores the role of hippocampal CA1 region’s TRPC4 in spatial working memory and modulation of oscillations in novel context. After injecting the developed shRNA TRPC4 into the mice CA1 area, behavioral and electrophysiological data were recorded in T-maze and linear track to study spatial working memory and oscillations modulation, respectively. While behavioral results showed a significant decrease (p<0.001) in spatial working memory performance, theta- gamma coupling analysis revealed a significant reduction (p<0.001) in theta-gamma coupling for TRPC4KD group compared to scramble group. The groups exhibited significant differences in cells' spatial information. In addition, the spike phase histogram showed different distribution, mean phase, and resultant vector length in the main stem for TRPC4 compared to scramble. Local field potential analysis in linear track revealed the modulation of beta oscillations via hippocampal CA1 TRPC4 channels. Collectively, the study results indicate that TRPC4 impairs gamma and beta oscillations, theta-gamma coupling, spikes' theta phase, and firing rate. While the impairment in gamma oscillations may alter plasticity according to previous reports, theta-gamma coupling was the main mechanism impaired during the spatial working memory task, leading to behavioral deficits.