Professor, Neurobiology and Behavior
Vice Chair, Neurobiology and Behavior
|Neurophysiology, Synaptic physiology of auditory cortex|
Our long-term goal is to understand the cellular basis of auditory perception and plasticity. To this end, we study how neurons in the auditory cortex process acoustic inputs, using electrophysiological, anatomical, behavioral and molecular methods.
Our current research addresses two main questions:
1. What is the cellular basis of the functional organization of auditory cortex?
Here we investigate the physiological and anatomical basis of systems-level organization asking, in particular, "How are receptive fields made?" This research continues on two fronts: first, we have developed a novel auditory thalamocortical brain slice preparation to study the synaptic processing of inputs to auditory cortex from the auditory thalamus. Second, in parallel, we conduct studies in vivo employing intracellular and extracellular recordings to determine the synaptic responses of auditory cortex neurons to acoustic stimulation. These complementary approaches are revealing how thalamocortical inputs integrate with long-distance ("horizontal") intracortical inputs to generate frequency receptive fields.
2. What role do acetylcholine receptors play in the development and function of auditory cortex?
This work stems from our discovery of two novel cholinergic mechanisms that function during development and in the adult, respectively: i) During development, nicotinic receptors appear transiently in the cortex to regulate glutamate release at pure-NMDA ("silent") synapses. This transient regulation may delineate critical period, during which exposure to exogenous nicotine disrupts subsequent function. Such disruption leads to auditory-cognitive deficits, which models deficits in children who are exposed to nicotine prenatally. ii) In the adult, we discovered that nicotinic receptors regulate axon excitability of myelinated thalamocortical axons, thereby regulating inputs to cortex. This facilitatory effect may contribute to the cognitive-enhancing effect of nicotine on adults.
Our ultimate goal is to achieve an understanding -- integrated from molecular to cellular to systems and behavioral levels -- of the role of auditory cortex and its regulation in higher brain function.
|Publications||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)|
|Intskirveli I, Metherate R, Cramer KS. (2011) Null mutations in EphB receptors decrease sharpness of frequency tuning in primary auditory cortex. PLoS One. 6:e26192.|
|Kawai HD, Kang HA, Metherate R. (2011) Heightened nicotinic regulation of auditory cortex during adolescence. Journal of Neuroscience, 31:14367-77.|
|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.|
|Liang, K., Poytress, B.S., Chen, Y., Leslie, F.M., Weinberger, N.M. and Metherate, R. (2006) Neonatal nicotine exposure impairs nicotinic enhancement of central auditory processing and auditory learning in adult rats. European Journal of Neuroscience 24: 857-866.|
|Rose, H.J., and Metherate, R. (2005) Auditory thalamocortical transmission is reliable and temporally precise. Journal of Neurophysiology 94:2019-2030.|
|Kaur, S., Rose, H.J., Lazar, R., Liang, K. and Metherate, R. (2005) Spectral integration in primary auditory cortex: laminar processing of afferent input, in vivo and in vitro. Neuroscience 134:1033-1045.|
|Metherate, R., Kaur, S., Kawai, H., Lazar, R., Liang, K., Rose, H.J. (2005) Spectral integration in auditory cortex: mechanisms and modulation. Hearing Research 206:146-158.|
|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|
|Metherate, R. (2004) Nicotinic acetylcholine receptors in sensory cortex. Learning & Memory 11:50-59.|
|Cruikshank, S.J., Rose, H.J. and Metherate, R. (2002) Auditory thalamocortical synaptic transmission, in vitro. Journal of Neurophysiology 87:361-84.|
|Aramakis, V.B., Hsieh, C.Y., Leslie, F.M. and Metherate, R. (2000) A critical period for nicotine-induced disruption of synaptic development in rat auditory cortex. Journal of Neuroscience 20:6106-6116.|
|Aramakis, V.B. and Metherate, R. (1998) Nicotine selectively enhances NMDA receptor-mediated synaptic transmission during postnatal development in sensory neocortex. Journal of Neuroscience 18:8485-8495.|
Society for Neuroscience; Association for Research in Otolaryngology (ARO)
Neurobiology and Behavior
Interdepartmental Neuroscience Program
|Research Center||Center for Hearing Research; Center for the Neurobiology of Learning and Memory|
|Link to this profile||http://www.faculty.uci.edu/profile.cfm?faculty_id=3220|