Raju Metherate

metherateOur 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.

UCI Faculty Profile