Research

Our research group investigates the assembly of auditory brainstem circuitry during normal development and its reorganization after injury.  We are particularly interested in the circuitry underlying sound source localization.  In birds, the pathway consists of projections from n. magnocellularis (NM) to n. laminaris (NL).  Axons from NM branch and contact NL on both sides of the brain.  Contralateral NM axon branches target ventral NL dendrites while ipsilateral NM axon branches target dorsal NL dendrites.  Delay lines in the contralateral axon branches, together with coincidence detection in NL neurons, allows for computation of interaural time differences, used in sound localization.  NL is a sheet of cells, about one cell thick, that is surrounded by a dense glial margin.  How does this circuit form?  What are the factors that guide NM axons to the appropriate targets in NL?  We study axon guidance molecules and other factors that regulate the formation of these nuclei and their synaptic connections.

An analogous pathway in the mammalian brainstem involves the ventral cochlear nucleus (VCN) and the medial superior olive (MSO).  In addition, in the lateral superior olive (LSO), the balance of excitation from the ipsilateral side and inhibition from the contralateral side are used to infer interaural level differences (ILDs), which are also used in sound localization.  A major component of both pathways includes inhibition from the ipsilateral medial nucleus of the trapezoid body (MNTB), which excitatory input from globular bushy cells in contralateral VCN.  Axons from these cells are long and terminate in a specialized ending known as the calyx of Held.

Early in development, MNTB cells receive multiple small inputs.  Some inputs are systematically eliminated until a single large calyx emerges on each MNTB cell.  How are excess synapses eliminated?  How do calyces form?  And how do new calyces form when input from VCN is removed?  We are currently investigating the roles of microglia in the maturation of these pathways.