Cholinergic Modulation of Reward Pathways. Acetylcholine transmission is crucial for learning/memory, attention, and cognitive processes, yet we know surprisingly little about the mechanisms by which ACh modulates circuits/behavior. The Drenan lab employs an interdisciplinary approach to understanding how ACh acts through receptors and circuits to modify cellular excitability, circuit function, and behavior.
Reward Pathway Nicotinic Receptors. We are interested in identifying nicotinic ACh receptors (nAChRs) in the mesolimbic reward pathway that mediate cholinergic modulation as well as the response to nicotine during tobacco product use. This includes studying nAChR interaction with diverse VTA cell types such as VTA glutamatergic neurons. We use physiology, CRISPR/Cas9 viral approaches, and behavior.
Mechanisms of Nicotine Withdrawal. We study neural circuits and nAChR neuropharmacology in the medial habenula-interpeduncular nucleus pathway, a key system involved in nicotine dependence and withdrawal. We use physiology, 2-photon microscopy, photoactivatable compounds, and in vivo Ca2+ imaging during behavior. Our goal is to identify how chronic nicotine changes circuits, leading to withdrawal symptoms during smoking cessation. Reducing withdrawal symptoms may improve smoking cessation rates.
Optical Approaches in Neuropharmacology. We are interested in developing novel optical techniques for studying channels and receptors in native tissue slices and in vivo. This includes photoactivatable versions of drugs and label-free methods for imaging neuronal membrane potential. We use 2-photon laser scanning microscopy and point photoactivation with additional laser lines (405, 470 nm).