Parallel Auditory Pathways in the Brain Stem

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DESCRIPTION (provided by applicant): The general goal of the proposed research is to understand how the function of the mammalian auditory midbrain, inferior colliculus (IC), relates to behavior. The IC integrates information from multiple auditory centers in the lower brainstem, from non-ascending auditory inputs from the opposite IC and auditory cortex and from motor-related structures. This integration is a first step in selecting for behaviorally relevant sounds. The non-ascending auditory inputs may modulate the sound-evoked responses of IC neurons, or even create specialized response properties. Although the inputs from all sources overlap to some degree, there are differences in their gradients of terminal density, which probably create functional gradients. We propose three specific aims, each designed to test a broad hypothesis related to the integration of the various auditory and motor inputs to the IC. Hypothesis 1: Response properties of IC neurons are determined by the ratios of input from different sources along a dorsoventral gradient. Specific Aim 1: We will use extracellular and intracellular recording of sound-evoked responses to examine the relation between selectivity for behaviorally relevant sound parameters, general response properties, gradients in input patterns, and immunocytochemical markers. Hypothesis 2: Sound-evoked responses of at least some IC neurons are modulated or created by input from non-ascending pathways. Specific Aim 2: To evaluate the contribution of these inputs to auditory processing, we will record sound-evoked responses of IC neurons before, during, and after reversible inactivation or electrical stimulation of the opposite IC or auditory cortex. Hypothesis 3: Sensory processing in the IC is modulated by motor-related inputs. Specific Aim 3: We will trace the projections of substantia nigra and globus pallidus to the IC, determine whether the inputs are excitatory or inhibitory, and record sound-evoked responses of IC neurons before, during and after reversible inactivation of substantia nigra. It is likely that the results of these experiments will be widely applicable to mammalian hearing. All mammals appear to have similar input gradients in the IC as well as inputs from motor pathways. Understanding how information from different sources is integrated in the IC could ultimately have implications for diagnosis and treatment of central hearing and language disorders.