Opioid receptor activation is one factor underlying the frequency dependence of mossy fiber LTP induction

The contribution of high-frequency synaptic activity to the induction of long-term potentiation (LTP) in the opioid peptide-containing mossy fiber projection was investigated in vivo in anesthetized rats. Because high-frequency mossy fiber activity is essential for both the release of opioid peptides and the induction of mossy fiber LTP, we investigated whether the activation of opioid receptors underlies the requirement of sustained high-frequency mossy fiber activity for LTP induction. Mossy fiber responses were found to have a distinct threshold for the number of 100 Hz pulses necessary to induce LTP, with bursts of 25-30 pulses being the minimum for LTP induction. Application of 1 nmol of the mu-opioid receptor agonist DAMGO to the CA3 region potentiated mossy fiber responses, but, unlike for mossy fiber LTP, this potentiation could be reversed by mu-opioid receptor antagonist CTOP. Stimulation of the mossy fibers with either a single burst of 15 pulses at 100 Hz or application of 100 pmol of DAMGO was ineffective in potentiating mossy fiber responses. However, delivery of a 15 pulse burst 10 min following DAMGO application was effective in potentiating mossy fiber responses. This potentiation was not reversed by CTOP and it occluded stimulation-induced LTP, suggesting that brief bursts delivered in the presence of DAMGO had induced mossy fiber LTP. The release of opioid peptides and the resulting activation of mu-opioid receptors is suggested as one factor that underlies the requirement of sustained high-frequency stimulation for the induction of mossy fiber LTP.(ABSTRACT TRUNCATED AT 250 WORDS)