OPIOID RECEPTOR MODULATION OF MOSSY FIBER SYNAPTOGENESIS - INDEPENDENCE FROM LONG-TERM POTENTIATION

Long-term potentiation (LTP) at the messy fiber-CA3 synapse of the rat hippocampus is an NMDA receptor-independent form of synaptic plastici ty that is sensitive to opioid receptor antagonists [12]. In the prese nt study, Timm's stain, a zinc detecting histological marker commonly used to infer synaptogenesis in the messy fiber projection, was used t o examine whether synaptogenesis occurs in response to messy fiber LTP induction in the adult rat in vivo. Seven days following the inductio n of messy fiber LTP by non-seizure-inducing high-frequency stimulatio n of the messy fibers, a prominent band of Timm's staining appeared bi laterally in the infrapyramidal region of the stratum oriens in area C A3. Staining was more prominent on the side contralateral to the stimu lation. Systemic administration of the opioid receptor antagonist nalo xone, sufficient to block messy fiber LTP induction, did not block the development of Timm's staining in the infrapyramidal region ipsilater al to stimulation, but it did block stimulation-induced increases in T imm's staining observed contralaterally. Systemic administration of (/-) CPP, a competitive NMDA receptor-antagonist, by contrast, did not block the induction of LTP and did not alter the increase in Timm's st aining observed either ipsilaterally or contralaterally. The increase in Timm's staining in the infrapyramidal region suggests that messy fi ber synaptogenesis occurs in response to non-seizure inducing stimulat ion. Synaptogenesis does not appear to be directly related to opioid r eceptor-dependent messy fiber LTP induction, because it occurs in the presence of naloxone which blocks LTP. The messy fiber synaptogenesis occurring contralaterally appears to be regulated by endogenous opioid peptides, because it is blocked by naloxone.