Professor, Neurobiology and Behavior
School of Biological Sciences

Associate Dean of Undergraduate Education
School of Biological Sciences

Neurophysiology, Synaptic physiology of auditory cortex, Nicotinic acetylcholine receptors

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.

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

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

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

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

Bieszczad KM, Kant R, Constantinescu CC, Pandey SK, Kawai HD, Metherate R, Weinberger NM, Mukherjee J. (2011) Nicotinic acetylcholine receptors in rat forebrain that bind (18) F-nifene: Relating PET imaging, autoradiography and behavior. Synapse. (in press)

Liang, K., Poytress, B.S., Weinberger, N.M. and Metherate, R. (2008) Nicotinic modulation of tone-evoked responses in auditory cortex reflects the strength of prior auditory learning. Neurobiology of Learning and Memory 90:138-146.

Kawai, H, Lazar, R. and Metherate, R. (2007) Nicotinic control of axon excitability regulates thalamocortical transmission. Nature Neuroscience 10:1168-1175.

Kaur, S., Lazar, R. and Metherate, R. (2004) Intracortical pathways determine breadth of subthreshold frequency receptive fields in primary auditory cortex. Journal of Neurophysiology 91:2551-2567

Cruikshank, S.J., Rose, H.J. and Metherate, R. (2002) Auditory thalamocortical synaptic transmission, in vitro. Journal of Neurophysiology 87:361-84.

Society for Neuroscience; Association for Research in Otolaryngology (ARO)

Interdepartmental Neuroscience Program

Neurobiology and Behavior

Center for Hearing Research; Center for the Neurobiology of Learning and Memory

Link to this profile
https://faculty.uci.edu/profile/?facultyId=3220

Last updated
07/08/2020