Cellular mechanisms of memory consolidation

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Although the hippocampus has long been known to play a key role in learning and memory, long-term declarative memories (e.g. names and faces, facts about the world, etc.) are thought to reside in neocortex. It is therefore assumed that some, as yet unknown, processes occur in the interaction between the hippocampus and the neocortex that affect the influence of synaptic inputs to neocortical neurons. This process depends on the activity in the parahippocampal structures such as the entorhinal and perirhinal cortices through which the information from the hippocampus must go. There are several difficulties in investigating memory consolidation but one that is not often mentioned is the fact that connections to the neocortex coming from the parahippocampal structures target predominantly layer 1 (and parts of layer 2/3). This has the consequence that synapses most likely to be important to memory consolidation arrive at the distal tuft dendrites of cortical pyramidal neurons making them very hard to examine.In this project, we aim to investigate these synapses in vivo and in vitro using a range of methodologies that have been developed in our laboratory. We will use optogenetic tools to visualize and influence synaptic input to tuft dendrites from the entorhinal cortex. Using various dendritic recording methods (electrophysiological and imaging) we will examine the postsynaptic influence of these inputs on subthreshold and suprathreshold activity. Lastly, we will design a behavioural task for investigating these connections in the intact animal during and after learning.