FREQUENCY-DEPENDENT ASSOCIATIVE LONG-TERM POTENTIATION AT THE HIPPOCAMPAL MESSY FIBER-CA3 SYNAPSE

The messy fiber-CA3 synapse displays an N-methyl-D-aspartate-receptor- independent mu-opioid-receptor-dependent form of long-term potentiatio n (LTP) that is thought not to display cooperativity or associativity with co-active afferents. However, because messy fiber LTP requires re petitive synaptic activity for its induction, we reevaluated cooperati vity and associativity at this synapse by using trains of messy fiber stimulation. Moderate-, but not low-, intensity trains induced messy f iber LTP, indicating cooperativity. Low-intensity messy fiber trains t hat were normally ineffective in inducing LTP could induce messy fiber LTP when delivered in conjunction with trains delivered to commissura l-CA3 afferents. Associative messy fiber LTP also could be induced wit h single messy fiber pulses when delivered with commissural trains in the presence of a mu-opioid-receptor agonist. Our findings suggest a f requency-dependent variation of Hebbian associative LTP induction that is regulated by the release of endogenous opioid peptides.