After a decade of fixation on long-term potentiation, neuroscientists are increasingly interested in other forms of persistent modulation of neurotransmission. We have recently observed a persistent 3-fold enhancement of Purkinje cell response to stimulation of parallel fibers minutes after a single 3-minute exposure of the isolated turtle cerebellum to a mild dose of glutamate. We propose here (1) to accurately document and characterize this form of neuromodulation and to ascertain whether it is related to long-term potentiation (very rarely reported in the cerebellum) or a distinct event; (2) to determine the glutamate receptor subtypes involved and the time-course of their interaction or possible interconversion; and (3) to determine whether the enhancement results from modulation of presynaptic neurotransmitter release mechanisms or from alteration of postsynaptic glutamate chemosensitivity, by comparing increases in postsynaptic potentials to the possible increases in responses to externally applied glutamate. Intracellular recording and iontophoretic techniques and specific receptor ligands or antagonists will be used. The study proposed here will contribute definitive findings to the better understanding of neuromodulation and also of inter-neuronal communication in the cerebellum.
NIH ExPorter
NIH ExPorter