Primary Department Affiliation: Neurobiology
Primary Research Area: Neurotransmitter and Neurotrophin Receptors and Cell Signaling
Learning, Memory, and Synaptic Plasticity
Ion Channels and Synaptic Function
Nicotinic Receptors in the CNS
The pivotal role of CNS nicotinic acetylcholine receptors (nAChRs) in tobacco addiction has focused our attentions on understanding the overall function of these receptors in the brain both under physiological and diseased conditions. nAChRs are ligand-gated ion channels composed of five individual protein subunits that cause neuronal excitation when bound and activated by synaptically released neurotransmitter, acetylcholine, or exogenous drugs like nicotine. Molecular biological studies have characterized at least ten receptor subunits that can be assembled together in numerous combinations giving rise to a wide variety of nAChRs with distinct functional roles. It is because of this diversity that nAChRs have been implicated in a range of CNS behaviors from pain sensation to learning and memory, and multiple pathological states such as epilepsy and schizophrenia.
High-resolution electrophysiological (patch-clamp) techniques combined with intracellular Ca2+ measurements provide the most powerful way of examining these receptors. The physiological and pharmacological properties of single and multiple nAChR channels in isolated membrane patches and whole cells can be fully resolved using these methods. The roles of nAChRs at both pre and postsynaptic zones of central synapses can be studied by recording from visually identified neurons in brain slice preparations. In collaboration with Dr. Michael W. Quick the electrophysiology is complemented by molecular biological approaches that allow the expression and characterization of known cloned nAChRs and the determination of nAChR RNAs from CNS neurons (by single cell RT-PCR). Thus, a full array of methods are available to address the following types of questions. How do nAChRs contribute to synaptic transmission and plasticity? How are nAChRs regulated by intracellular Ca2+, phosphorylation and the cytoskeleton? How does chronic nicotine affect the long-term functioning of the various nAChRs?
Robin A.J. Lester received his Ph.D. in Pharmacology from the University of Bristol, UK in 1988. Following a Research Assistant Professor position at Baylor College of Medicine, he joined UAB in 1995. He is presently a Professor of Neurobiology.