Entorhinal cortex, acetylcholine and the coding of time and space for memory

Michael Hasselmo

(Boston Univeristy)

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Date: Wednesday March 4, 2015


Memory function is impaired by lesions of the entorhinal cortex, and also by lesions of the modulatory input from medial septum. My research focuses on understanding circuit mechanisms in the entorhinal cortex that might contribute to memory function. Neurophysiological data demonstrates cholinergic activation of intrinsic persistent spiking in entorhinal neurons. This persistent spiking could maintain memory over time in tasks such as delayed matching to sample and trace conditioning and enhance encoding of episodic memory. These effects might also contribute to coding of time in the phenomenon of “time cells” in the entorhinal cortex and hippocampus. Cellular mechanisms might also be relevant to the coding of spatial dimensions by grid cells. Attractor dynamic models of grid cells need a mechanism for spiking interactions to persist over interspike intervals. The maintenance of attractors could be supported by persistent spiking or rebound spiking in entorhinal neurons. Loss of cholinergic activation of persistent spiking could underlie the loss of grid cells during inactivation of medial septum, as supported by loss of grid cell firing after cholinergic blockade. These intrinsic properties could also contribute to the phenomenon of theta phase precession in grid cells and theta cycle skipping observed in rodent medial septum and entorhinal cortex.

Created: Wednesday, March 4th, 2015