This new research proposal intends to clarify the precise organization, input and output, and evolutionary significance of the cerebellar-like neuronal microcircuit recently identified in the mammalian cochlear nuclear complex, thus complementing previous accomplishments of the P.I.'s laboratory. The projects will utilize classical neuranatomical problem solving procedures (quantitative electron microscopy and tract-tracing ), coupled to immunocytochemical detection of chemical neuronal phenotypes and cell population specific neuronal labeling, two modern approaches made possible by advances in molecular neurobiology. The program attempts to: 1) morphologically identify and chemically characterize the multiple sources of the afferent fibers that activate the granule-cartwheel-neuron system in the superficial regions of the ventral and dorsal cochlear nucleus, including the olivocochlear neurons; 2) determine whether the inhibitory cartwheel neurons, in addition to the known synapses to the principal, excitatory, pyramidal (or fusiform) cells, provide synapses also to the deep, tuberculoventral neurons that produce inhibition in the ventral cochlear nucleus; 3) clarify the cytology and synaptology of the newly discovered cholinergic system of the cochlear nucleus, and the relations of the cholinergic innervation to the granule-cartwheel cell system; 4) study the granule-cartwheel-- pyramidal-tuberculoventral cell system in an animal (the muskrat-like """"""""mountain beaver"""""""", the most primitive among rodents, not to be confused with the common beaver!) where the granule cell domain is extraordinarily developed; 5) exploit the new data on the morphological and chemical phenotypes of neurons in the deep dorsal cochlear nucleus and the superior olivary complex to more clearly establish the typology of neurons in these regions and their respective synaptic networks. This research program has several neurological implications: by clarifying the neurobiology of the cochlear nucleus microcircuits, which are the first to undergo atrophy after peripheral nerve lesion, it helps understanding the mechanisms for its maintenance, and the evolutionary changes leading to perinatal degeneration of the granule cell system in the normal human; by unraveling the complexities of the olivocochlear system, it will contribute to understanding the mechanisms of central control and acoustic injury.
