Abstract

ABSTRACT

Cholinergic modulation of the superficial layers of the parasubiculum

Stephen D. Glasgow, Ph.D.
Concordia University, 2011

Recent evidence suggests that the parahippocampal area, including the entorhinal cortex and parasubiculum, may play a crucial role in spatial processing and memory formation. However, little is known about the basic cellular and network properties of the parasubiculum, an isocortical brain region that receives input from the hippocampus and other subcortical regions associated with spatial navigation, and projects exclusively to the superficial layers of the entorhinal cortex. Neurons in layer II of the parasubiculum demonstrate theta-frequency membrane potential oscillations at near-threshold voltages that are generated via an interplay between a persistent Na+ current and the hyperpolarization-activated cationic current Ih, and these rhythmic fluctuations in membrane potential may contribute to the generation of oscillatory local field potentials. Further, the parasubiculum receives strong cholinergic projections from the medial septum. Acetylcholine has been linked to theta-frequency oscillations via regulation of cellular and network dynamics through membrane depolarization, while concurrently suppressing excitatory synaptic transmission, and it is likely that cholinergic receptor activation has similar effects in the parasubiculum. I found that activation of cholinergic receptors depolarizes layer II cells of the parasubiculum by exerting numerous effects on K+ channels, including IM and IKir, however also suppresses incoming excitatory synaptic transmission from the CA1. These results indicate that increases in cholinergic tone during network-level theta-frequency oscillations in the parasubiculum may increase neuronal excitability by exerting strong effects on postsynaptic conductances, but may also regulate network dynamics by reducing the strength of incoming afferents.