This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We have previously established that growth of the calyx of Held, perhaps the largest synaptic terminal in the mammalian brain, occurs over a 48 hour period from postnatal day (P) 2 to P4. These terminals grow onto and cover large portions of the somata of principal neurons in medial nucleus of the trapezoid body (MNTB) in the auditory brainstem. Calyx growth requires tremendous cellular resources to achieve the morphological expansion of the terminals and the establishment of hundreds of active zones. During this process, only one of many converging presynaptic inputs will grow and form a calyx terminal, and thus rapidly establish 1:1 innervation that persists through adulthood, well before sensory input is detected and transmitted through this circuit. Our long-range goal is to reveal structural transformations and cellular communication that characterize contact of the calycigenic growth cone with its target and the early stages of synapse assembly and stabilization at large nerve terminals in the auditory brainstem. Our central hypothesis is that competition among calycigenic inputs precedes expansion of the terminal over the cell body to form a calyx.
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