The long term goal of this project is to understand the structural and neurochemical circuitry of the auditory brainstem in sufficient detail that we can make intelligent structure/function correlations and predict how each part contributes to auditory signal processing. In the present proposal, we will concentrate on the nuclei of the lateral lemniscus (NLL). The NLL provide both monaural and binaural inputs to the auditory midbrain, i.e., the central nucleus of the inferior colliculus (ICc). They are the second largest source of inputs to the ICc (surpassed only by projections from the cochlear nucleus) and are its single largest source of inhibitory inputs. Emerging evidence suggests that inhibition may have many roles in shaping the responses of ICc neurons, including frequency tuning, temporal response patterns, and rate-intensity functions. Inhibition from the dorsal nucleus of the NLL has been implicated in binaural suppression in the ICc. In addition to their main projections to the ICc, the NLL also contribute extralemniscal projections to the auditory thalamus and superior colliculus, and descending projections to the cochlear nucleus and superior olivary complex. Yet, of all regions of the central auditory system, the NLL are the least understood in terms of their cellular composition and cellular connectivity. In the present proposal, we will characterize the cellular architecture of the NLL and correlate these findings with cellular differences in transmitter type and synaptic target. We will also examine the afferent inputs to the crossed and uncrossed projections of the dorsal nucleus of the NLL, so that we can infer something about the types of information being carried to the ICc by each component of its projections. These experiments are designed to bridge the gap between purely morphological and purely neurochemical studies by examining the cytochemistry of morphologically defined neurons in the NLL. In addition, by examining the afferent and efferent connections of these morphologically and cytochemically defined neurons, we hope to learn something about the types of information that each transmits to its synaptic targets. This should better enable us to relate our observations to neurophysiological and neuropharmacological investigations, and to predict how each component of the NLL projections contributes to monaural and binaural signal processing.
