Endogenous opioids regulate long-term potentiation of synaptic inhibition in the dentate gyrus of rat hippocampus

Abstract

Long-term potentiation (LTP) of excitatory transmission in the hippocampus has been extensively studied as a synaptic model of learning and memory. Here we report a new form of LTP in which inhibitory synaptic signals are potentiated following tetanic stimulation of an opioid-containing excitatory pathway in the presence of opioid antagonists. The lateral perforant path (LPP) was stimulated at the dentate outer molecular layer of hippocampal slices. Evoked synaptic currents were recorded from dentate granule cells using whole- cell voltage-clamp techniques. A high-frequency stimulus train (100 Hz, 1 sec) delivered to the LPP in the presence of naloxone (1 microM) was found to induce a long-lasting potentiation (20 min to 2 hr) in the amplitude of gamma-aminobutyric acidA (GABAA) receptor-mediated inhibitory postsynaptic currents (IPSCs) of granule cells. Such a potentiation was not observed when tetanizing the LPP in control medium. Naloxone-revealed LTP of LPP-evoked IPSCs did not depend upon the presence of granule cell discharge, and was not accompanied by potentiation of mossy fiber-evoked IPSCs, indicating that feedforward, but not feedback, inhibitory circuits were involved. Induction of this LTP could be completely blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonopentanoic acid (D-APV). However, it was not significantly affected by hyperpolarization of granule cells. These results suggest that LTP may occur at the excitatory synapses between LPP terminals and GABAergic interneurons, rather than at the inhibitory synapses between interneurons and granule cells. Further examination using selective opioid antagonists demonstrated that blocking delta, but not mu and kappa, receptors is critical for inducing LTP of IPSCs in granule cells.

Hormonal regulation of delta opioid receptor immunoreactivity in interneurons and pyramidal cells in the rat hippocampus

“…Namely, females, with fewer DORs available for activation in granule cells would be more likely to transmit perforant path excitatory inputs than male counterparts, as DOR activation directly hyperpolarizes granule cells to modulate output (Piguet & North, 1993; Bausch & Chavkin, 1997). In spite of intense electrophysiological investigation and in contrast to the DG (Xie & Lewis, 1995b) and CA3 (Moore et al, 1994), direct opiate receptor effects have rarely been detected on CA1 pyramidal cells. Instead, as aforementioned, DOR activation is thought to increase the excitability of CA1 pyramidal cells by reducing presynaptic inhibition (Madison & Nicoll, 1988; Neumaier et al, 1988; Svoboda & Lupica, 1998; Svoboda et al, 1999).…”

Opioid Receptor-Dependent Sex Differences in Synaptic Plasticity in the Hippocampal Mossy Fiber Pathway of the Adult Rat

“…Stock solutions were diluted in NaCl-ACSF on the day of the experiment to reach their final concentration (naloxone, 1 ⌴; CTOP, 300 nM; NTI, 1 M). The doses were chosen because they have been used to examine maximal effects in hippocampal slices at opioid receptors while maintaining specificity (Watson and Lanthorn, 1993;Xie and Lewis, 1995;Jin and Chavkin, 1999;McQuiston, 2007).…”

Recent advances on the δ opioid receptor: from trafficking to function

“…Further electrophysiological studies demonstrate that DOPrs are required to induce long‐term depression of parvalbumin‐expressing neurons within CA2 (Piskorowski and Chevaleyre, ) and inhibit the excitatory temporoammonic pathway from the entorhinal cortex to CA1 (Rezai et al ., ). DOPrs are also critical for the induction of long‐term potentiation in dentate granule cells (Xie and Lewis, ). At the behavioural level, mice lacking DOPrs show impaired hippocampal and striatal‐based learning and motor tasks (Le Merrer et al ., ).…”