TRPC4 Channel Knockdown in the Hippocampal CA1 Region Impairs Modulation of Beta Oscillations in Novel Context

SIMPLE SUMMARY: Memory is a fundamental cognitive function we need for everyday life. Since we process so much information each day, it is believed that our memory system selects only relevant information to encode in order to avoid overload. In this work, we study the molecular mechanism supporting this selective memory encoding. It is believed that memory encoding occurs mainly when we encounter a new unexpected condition: a novel context. In a novel context, the hippocampus, which is crucial for memory function, intensifies a specific rhythmic activity called beta oscillations. While these beta oscillations are believed to support memory encoding, the molecular mechanisms underlying this increase in beta oscillations are not yet understood. We demonstrate that a specific type of membrane ionic channel called transient receptor potential canonical 4 (TRPC4) supports the modulation of beta oscillation in the hippocampus, indicating that TRPC4 channels play a role in novelty-related memory encoding. ABSTRACT: Hippocampal local field potentials (LFP) are highly related to behavior and memory functions. It has been shown that beta band LFP oscillations are correlated with contextual novelty and mnemonic performance. Evidence suggests that changes in neuromodulators, such as acetylcholine and dopamine, during exploration in a novel environment underlie changes in LFP. However, potential downstream mechanisms through which neuromodulators may alter the beta band oscillation in vivo remain to be fully understood. In this paper, we study the role of the membrane cationic channel TRPC4, which is modulated by various neuromodulators through G-protein-coupled receptors, by combining shRNA-mediated TRPC4 knockdown (KD) with LFP measurements in the CA1 region of the hippocampus in behaving mice. We demonstrate that the increased beta oscillation power seen in the control group mice in a novel environment is absent in the TRPC4 KD group. A similar loss of modulation was also seen in the low-gamma band oscillations in the TRPC4 KD group. These results demonstrate that TRPC4 channels are involved in the novelty-induced modulation of beta and low-gamma oscillations in the CA1 region.