The hippocampus and entorhinal cortex, which are part of the medial temporal lobe (MTL), support memory and spatial navigation functions. Our research focuses on neural computation underlying cognitive functions of the MTL, combining in vitro and in vivo electrophysiological recordings with computational simulations. Since the MTL is crucially involved in Alzheimer’s disease and temporal lobe epilepsy, studying neural computation in the MTL is central not only to understanding of cognitive functions and its engineering applications, but also to developing treatments for dementia and epilepsy.
The ability to associate events that are temporally apart, requires an intact hippocampus. Our current major focus is on the roles of transient receptor potential cation (TRPC) channels in temporal association memory. TRPC channels are abundant in hippocampal principal cells (Fig. 1A). We have recently shown that TRPC channels modulate dynamical properties of hippocampal pyramidal cells known as persistent firing (Fig. 1B). Computational simulations have indicated that TRPC channels play crucial roles in shaping neural network activity, allowing persistent firing to co-exist with the theta oscillations. We plan to further our understandings of the contributions of TRPC channels on behavioral levels using TRPC channel manipulations in vivo.
Fig1. (A) Immunohistochemical staining of TRPC5 channel in hippocampal CA1 cells. (B) Persistent firing in a hippocampal CA1 pyramidal cell.
Grid cells in the medial entorhinal cortex (MEC) are believed to support spatial navigation. It has been proposed that grid cell firing emerges through path integration, which is the ability to update spatial representation by using idiothetic cues. MEC layer II has mainly two different types of cells: pyramidal and stellate cells. However, the cellular mechanisms supporting path integration and grid cell formation remain unknown. Oscillatory properties of MEC layer II neurons and persistent firing may support path integration (Fig. 2). We have recently shown that properties of MEC layer II neurons such as the spike adaptation ratio are different along the dorso-ventral axis, indicating these cellular properties may underlie differences in grid cell spacing.
Fig2. (A1-3) Subthreshold membrane potential oscillations recorded from an MEC layer II neuron at different baseline membrane potentials. (B) Power spectra of subthreshold oscillations measured at different baseline membrane potentials.
It has been suggested that the MTL supports memory formation through two distinct processes: encoding and consolidation. Hippocampal neurons switch their firing mode from "place cell" or "time cell" activity during encoding to the temporally compressed "replay" activity during consolidation. The prevailing theory suggests that the level of the neuromodulator acetylcholine triggers this transition of operational modes. Our theoretical and computational work suggests that cholinergic modulations of intrinsic cellular properties, including the TRPC and potassium channels, may support the transition.
Fig3. Schematic drawing of neural network activity during consolidation (replay activity) and encoding stages (place and time cell firing).