Cellular mechanisms underlying spatial processing in medial entorhinal cortex
Heys, James Gerard
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Functional brain recordings from several mammalian species including rodents, bats and humans demonstrate that neurons in the medial entorhinal cortex (mEC) represent space in a similar way. Single neurons in mEC, termed 'grid cells' (GCs), fire at regular repeating spatial intervals as the animal moves throughout the environment. In rodents, models GCs have been inspired by research that suggests a relationship between theta rhythmic electrophysiology in mEC and GC firing behavior. The h current time constant and frequency of membrane potential resonance (MPR) changes systematically along the dorsal to ventral axis of mEC, which correlates with systematic gradations in the spacing of the GC firing fields along the same anatomical axis. Despite significant efforts, the mechanism generating this periodic spatial representation remains an open question and the work presented in this thesis is directed towards answering this question One major class of models that have been put forth to explain the grid pattern use interference between oscillations that are frequency modulated as a function of the animal's heading direction and running speed. Parts one and two of this thesis demonstrate how cholinergic modulation of MPR frequency could account for the expansion of grid field spacing that occurs during exploration of a novel environment. The result from these experiments demonstrate that activation of muscarinic acetylcholin receptors produces a decrease in the h current amplitude which causes a decrease in the MPR frequency. Recently unit recordings have shown that GC firing pattern may exist in the mEC of the bat in the absence of these characteristic theta-rhythmic physiological mechanisms. The third section of the thesis details experiments in bat brain slices that were conducted to investigate the cellular physiology of principal neurons in layer II of mEC in the bat and directly test or intrinsic cellular mechanisms that could generate theta in mEC of the bat. Together this work reveals that significant h current is present in rodents and bats. However, the time course of the h current may differ between species such that theta band membrane potential resonance is present in the rodents but is not produced in bat neurons in mEC.
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