The inferior colliculus (IC) is a midbrain structure where virtually all ascending auditory information terminates in route to the auditory cortex. Our ultimate objective is to understand the cellular mechanisms that underlie sound processing in the IC. This research project will employ a diverse set of experimental approaches. (1) Experiments in the intact animal using physiological and neuroanatomical methods will show that the IC contains functional zones where the response properties of the neurons are directly related to the brainstem inputs. Experiments using axonal labels will show that major inhibitory inputs to the IC terminate in separate functional zones. Experiments using retrograde cell markers will show which inputs to the IC are related to neurons with different binaural and monaural response properties. (2) Experiments in the intact animal will study the outputs of the functional zones in the IC and may implicate the IC in pathways that lead to two different types of higher-level auditory processing: a binaural pathway conveying information about sound location, and a monaural pathway that conveys information about the spectral properties of complex sounds. (3) Experiments in a brain slice preparation of the IC will investigate neuron types defined by unique discharge patterns and specific potassium currents. These cell types also differ in their synaptic responses. The experiments will determine if the different synaptic responses are due to the synaptic inputs (mediated by ligand-gated postsynaptic receptors) or to the membrane properties (related to voltage-activated ion channels). Responses will be examined to synaptic inputs (evoked by stimulation of the lateral lemniscus) and to artificial synaptic inputs (that simulate the synaptic currents without activating the postsynaptic receptors). (4) Experiments in a brain slice preparation will investigate structure-function relationships at the morphological, molecular, and transmitter level. These experiments will morphologically label functional cell types and then test them for expression of ion channel subunits and transmitter content. (5) Finally, experiments in the intact animal will use intracellular recording to allow direct comparisons to the brain slice. We will learn whether the IC cell types are found in the adult animal, and how the intracellular responses are related to electrical stimulation of the lateral lemniscus and stimulation by monaural and binaural sounds.
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