To comprehend the brain’s dynamic physiology, we must understand the mechanisms underlying neuronal excitability, crucial for neurons’ electrical activation during synaptic communication. Of particular interest is controlled potassium current leakage via two-pore domain potassium channels which finely modulate the intrinsic excitability of neurons. TRESK, the latest discovered channel of the K2P family, has a well-characterized pivotal role in nociception. Intriguingly, it also exhibits widespread expression throughout central nervous system, yet its function within the brain has remained unexplored. We are combining in-situ hybridization RNAscope technique and electrophysiology experiments to examine the contribution of TRESK to hippocampal excitability. We observed TRESK mRNA in excitatory and inhibitory neurons along the CA1-CA3 regions and dentate gyrus. Functionally, field potential and whole-cell patch-clamp recordings in acute slices revealed that TRESK knockout mice exhibit decreased paired-pulse facilitation and impaired long-term synaptic plasticity in the Schaffer Collateral pathway. Additionally, in the absence of TRESK, CA3 pyramidal neurons displayed enhanced excitability via reduced rheobase current and a tendency for a more depolarized resting membrane potential. Accordingly, there was an increased number of cells that were spontaneously active and they had higher firing frequencies compared to control slices. We are currently exploring the role of TRESK in GABAergic cells. Our findings highlight the involvement of TRESK in hippocampal excitability and synaptic plasticity. These data serve as a foundation for future experiments to elucidate the role of TRESK channels in hippocampal intrinsic plasticity, which will provide insights into principles governing the dynamics of neural networks in memory formation.