SYNAPTIC MECHANISMS UNDERLYING SENSORY TRANSDUCTION

The main aim of this project is to provide a clearer understanding of the cellular and molecular events that are responsible for the transduction of sensory stimuli at the peripheral terminals of cutaneous afferent neurons. Several classes of cutaneous afferent neurons have been defined physiologically and, in many instances, the receptive properties of these neurons are correlated with morphological specializations of the peripheral endings. However, the mechanisms of transmission of information between specialized transduction cells and primary sensory endings remain unclear. Electrophysiological and immunological methods will be used to examine chemical transmission and cellular interactions at synaptic sites between two classes of transduction cell and their sensory innervation. These are the Merkel cell-sensory neuron junction and the junction between the taste bud receptor cell and its gustatory innervation. Immunological techniques will be used to identify and purify Merkel cells and taste buds and to maintain these cells in dissociated tissue culture. The biochemical, cytochemical and membrane properties of these cells will be characterized and compared with the properties of these cells in situ. Receptor cells will be grown in co-culture with appropriate classes of primary sensory neurons obtained from the dorsal root ganglion or the trigeminal ganglion, and identified using monoclonal antibodies that react with cell-surface antigens that are expressed selectively on each cell type. Pharmacological agents will be used to provide information on the identity of the transmitters released at the transduction cell-sensory neuron synapse. Intracellular recording will be used to monitor the sensitivity of sensory neurons to transmitters released from identified transduction cells. Similar approaches will be used to examine reciprocal actions on transduction cells of chemical mediators released from sensory neuron terminals.