Modulation of medial entorhinal cortex layer II neurons by two cation non-specific currents : IH and INCM

Neurons from layer II of the entorhinal cortex (EC} occupy a pivotal position in the medial temporal lobe gating the flow of neocortical information into the hippocampus. Previous "in vivo" studies had shown that EC layer II generates theta rhythmicity, and "in vitro" investigations have demonstrated that the main population of layer II projection neurons, the stellate cells, display intrinsic theta-like autopacemaker properties. EC layer II cells receive important subcortical serotoninergic and cholinergic input from the dorsal raphe and basal forebrain, respectively, and these inputs are known to affect the population oscillatory behaviour of cortical neurons, including the "theta" rhythm. Using pharmacological and voltage-clamp techniques in the EC slice preparation, the ionic mechanisms that contribute to the generation of intrinsic oscillations in the layer II stellate cells, and whether this mechanism was affected by serotoninergic neuromodulatory influences was investigated. As well, the aspects of how cholinergic muscarinic actions depolarize EC layer II neurons and may affect the oscillatory firing properties of these cells were also investigated. This Thesis confirmed that EC layer II stellate cells display a robust time-dependent inward rectification and demonstrated that this rectification is generated by a hyperpolarization activated non-specific inward cation current known as IH. I H, in conjunction with a low threshold persistent Na+ current was established to play a crucial role in the generation of the theta-like subthreshold oscillations. Next, similar to other cortical neurons, serotonin enhances IH by producing a small but significant positive shift in its activation curve. Finally, and with respect to cholinergic actions, the mechanism of cholinergic depolarization consists of both the block of a K+ conductance and, primarily, the activation of a noise non-specific cationic conductance, distinct from IH, named I NCM.