A PRESYNAPTIC LOCUS FOR LONG-TERM POTENTIATION OF ELEMENTARY SYNAPTICTRANSMISSION AT MOSSY FIBER SYNAPSES IN CULTURE

The complex circuitry of the CA3 region and the abundance of collatera l connections has made it difficult to study the messy fiber pathway i n hippocampal slices and therefore to establish the site of expression of long-term potentiation at these synapses. Using a novel cell cultu re system, we have produced long-term potentiation of the elementary s ynaptic connections on single CA3 pyramidal neurons following tetanic stimulation of individual dentate gyrus granule cells. As is the case for the hippocampal slice, this potentiation was independent of N-meth yl-D-aspartate receptor activation, was simulated by application of fo rskolin, and its induction did not require any modulatory input. The i ncrease in synaptic strength was accompanied by a reduction in the num ber of failures of transmission and by an increase in the coefficient of variation of the responses and was prevented by presynaptic injecti on of an inhibitor of protein kinase A. These findings show that messy fiber long-term potentiation has a presynaptic locus and that its exp ression is dependent on protein kinase A.