Cellular and Network dynamics of medial temporal lobe memory structures

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The anatomical connections between the neocortex (nCTX) and the hippocampus (HPC), centered in the medial temporal lobe (MTL), are thought to be the brain's hardware for the formation and storage of certain forms of memory.  The disruption of neural activity in these circuits causes both anterograde and retrograde amnesic symptoms. Therefore, an understanding of how memory formation and storage takes place requires an understanding of the normal activity patterns of this circuitry. During the performance and retention of memory tasks MTL neurons display prominent oscillatory synchronization whose frequency parameters depend upon behavioural state.  These different patterns of state-dependent activity are due to fluctuating levels of endogenous neuromodulators. The implication of these different oscillatory states in the MTL is that different patterns may predispose this circuitry for different information processing purposes.  In fact, certain patterns such as the theta/gamma rhythm have been shown to optimize the expression of plasticity in this circuitry.      The objective of this research is to examine, at the cellular and circuit level, the electrophysiological properties and state-dependent neuromodulation of structures within the MTL, focusing on the entorhinal cortex. The EC is a nodal element of the MTL since it forms a bi-directional interface between the nCTX and HPC. Cells within the EC are subject to state-dependent neuromodulatory influences that affect their intrinsic properties, their network interactions and thus, the processing of information. While our knowledge of the intrinsic properties of EC principal neurons is quite sophisticated, our understanding of the EC network and its dynamics is still limited. The aim of this proposal is to study the synaptic interactions between EC cells and the effects of cholinergic and serotonergic neuromodulation upon them.      The results obtained via these methods will yield insights into the dynamic processing characteristics within the MTL and may provide hints as to the brain mechanisms involved in memory formation and/or storage.