The long-term goal of my lab is to understand how nicotinic acetylcholine receptors (nAChRs) regulate neural processing in auditory cortex, and to develop nicotine-based drug therapies for auditory processing disorders. Our research accomplishments highlight novel cellular and systems-level mechanisms of nicotinic modulation. These mechanisms in auditory cortex and subcortical structures (notably the thalamocortical pathway) integrate to produce a remarkable result: systemic nicotine increases gain and sharpens receptive fields in primary auditory cortex (e.g., Askew et al. 2017). Going forward, the lab has two broad goals: first, to understand which nAChR subtypes and neuron sub-classes are responsible for the effects of nicotine at the systems and behavioral-cognitive levels. In particular, we wish to determine how the most striking of nicotine’s cellular actions—selective and robust excitation VIP interneurons (Askew et al. 2019)—contributes to nicotine’s physiological effects. A second broad goal is translational: to determine if nicotine’s effects may enable a first-ever drug treatment for central auditory processing disorders that involve diminished auditory attention. Given that systemic nicotine mimics the effects of auditory attention on receptive fields in A1 of humans and nonhuman primates, we wish to determine if nicotine may enhance auditory attention, in particular during aging and disorders associated with reduced auditory-cognitive function. To these ends our research focuses on mouse in vivo and in vitro electrophysiology and, in collaboration with other labs, nicotine’s effects in behaving animals and humans.

Intskirveli, I. and Metherate, R. (2012) Nicotinic neuromodulation in auditory cortex requires MAPK activation in thalamocortical and intracortical circuits. Journal of Neurophysiology 107:2782-2793. PMCID: PMC3362282

Askew, C.E., Intskirveli, I. and Metherate, R. (2017) Systemic nicotine increases gain and narrows receptive fields in A1 via integrated cortical and subcortical actions. eNeuro 4:e0192-17.2017 1–18. PMCID: PMC5480142

Askew, C.E., Lopez, A.J., Wood, M.A and Metherate, R. (2019) Nicotine excites VIP interneurons to disinhibit pyramidal neurons in auditory cortex. Synapse 73:e22116. PMCID: PMC6767604

Pham C.Q., Kapolowicz M.R., Metherate R. and Zeng F.G. (2020) Nicotine enhances auditory processing in healthy and normal-hearing young adult nonsmokers. Psychopharmacology (Berl) 237:833-840. doi: 10.1007/s00213-019-05421-x. PMID: 31832719