Nicotinic ACh receptors in the hippocampus: role in excitability and plasticity

The nicotinic ACh receptors (nAChRs) are in the cys-loop family of ligand-gated ion channels. They are widely expressed throughout the brain, including in the hippocampus where they are thought to be involved in regulating excitability, plasticity, and cognitive function. In addition, dysfunction in hippocampal nAChRs has been linked to a variety of neurological disorders and diseases, including Alzheimer's disease, schizophrenia, and epilepsy. In order to understand how to treat nAChR-related disorders and diseases, it is critical to understand how these receptors participate in normal brain function; this entails not only understanding the biophysical properties of ion channel function and their pattern of expression but also how these receptors are regulating excitability and circuit behavior.

The primary cholinergic input to the hippocampus comes from the medial septum and diagonal band of Broca; however, the mechanistic details are unknown of how activation of cholinergic receptors, either through exogenous nAChR ligands or the activation of endogenous acetylcholine release, regulates hippocampal network activity. This entails direct study of the excitatory and inhibitory neuronal networks, as well as the role of nonneuronal cells, in regulating hippocampal function.

Here, I will review the latest work from my laboratory in which we have attempted to do just that, with the overall goal of learning more about the role of the hippocampal nAChR in synaptic plasticity.