A ROLE FOR CAMP IN LONG-TERM DEPRESSION AT HIPPOCAMPAL MOSSY FIBER SYNAPSES

Mossy fiber synapses on hippocampal CA3 pyramidal cells, in addition t o expressing an NMDA receptor-independent form of long-term potentiati on (LTP), have recently been shown to express a novel presynaptic form of long-term depression (LTD). We have studied the mechanisms underly ing mossy fiber LTD and present evidence that it is triggered, at leas t in part, by a metabotropic glutamate receptor-mediated decrease in a denylyl cyclase activity, which leads to a decrease in the activity of the cAMP-dependent protein kinase (PKA) and a reversal of the presyna ptic processes responsible for mossy fiber LTP. The bidirectional cont rol of synaptic strength at mossy fiber synapses by activity therefore appears to be due to modulation of the cAMP-PKA signaling pathway in mossy fiber boutons.