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Long-term Potentiation of Perforant Pathway-dentate Gyrus Synapse in Freely Behaving Mice
Published on: November 29, 2013
Mu opioid receptor-mediated modulation of synaptic currents in dentate granule cells of rat hippocampus
C W Xie1, R A Morrisett, D V Lewis
1Duke University Medical Center, Durham, North Carolina 27710.
Abstract:
1. The effect of a selective mu opioid agonist, [N-MePhe3-D-Pro4]morphiceptin (PL017), on synaptic transmission in the dentate gyrus was examined in hippocampal slices. Synaptic currents were evoked by stimulation of the outer molecular layer and recorded from granule cells using whole-cell voltage-clamp techniques. 2. Monosynaptic inhibitory postsynaptic currents (IPSCs) were evoked in the presence of D(-)-2-amino-5-phosphonovaleric acid (D-APV), and N-methyl-D-aspartate (NMDA) receptor antagonist, and 6,7-dinitroquinoxaline-2,3-dione (DNQX), a non-NMDA type of glutamate receptor antagonist. The IPSCs consisted of a gamma-aminobutyric acid (GABA)A receptor-mediated early component and a GABAB receptor-mediated late component. 3. Bath application of PL017 (0.3-3 microM) induced a dose-dependent reduction in the amplitude of both early IPSCs (21-56%) and late IPSCs (43-81%). These effects could be reversed by the opiate antagonist naloxone (1 microM) or prevented by the selective mu antagonist beta-funaltrexamine hydrochloride (10 microM). 4. NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) were revealed in the presence of DNQX and the GABAA antagonist bicuculline methiodide. PL017 (3 microM) caused a 35% reduction in the amplitude of NMDA EPSCs. NMDA receptor-mediated population EPSPs recorded extracellularly were also inhibited by 3 microM PL017 to a similar degree. 5. Non-NMDA receptor-mediated EPSCs were demonstrated in the presence of D-APV and bicuculline methiodide. The amplitude of non-NMDA EPSCs was not affected by PL017.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
The mu opioid agonist PL017 inhibits synaptic transmission in the dentate gyrus by reducing both inhibitory and excitatory postsynaptic currents. These effects are reversed by naloxone, indicating a role for mu opioid receptors in synaptic plasticity.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Synaptic transmission in the dentate gyrus is crucial for learning and memory.
- Opioid receptors, particularly mu opioid receptors, are known to modulate neuronal activity.
Purpose of the Study:
- To investigate the effects of a selective mu opioid agonist, [N-MePhe3-D-Pro4]morphiceptin (PL017), on synaptic transmission in the dentate gyrus.
Main Methods:
- Hippocampal slices were used to record synaptic currents from granule cells.
- Whole-cell voltage-clamp techniques were employed to measure inhibitory postsynaptic currents (IPSCs) and excitatory postsynaptic currents (EPSCs).
- Pharmacological agents including D-APV, DNQX, and bicuculline methiodide were used to isolate specific receptor-mediated currents.
Main Results:
- PL017 dose-dependently reduced the amplitude of both early (GABAA-mediated) and late (GABAB-mediated) IPSCs.
- PL017 significantly inhibited NMDA receptor-mediated EPSCs but did not affect non-NMDA receptor-mediated EPSCs.
- The inhibitory effects of PL017 on synaptic transmission were reversed by naloxone and prevented by beta-funaltrexamine hydrochloride.
Conclusions:
- Selective mu opioid receptor activation by PL017 modulates synaptic transmission in the dentate gyrus.
- PL017 inhibits both GABAergic and glutamatergic (NMDA receptor-mediated) synaptic transmission.
- These findings highlight the role of mu opioid receptors in regulating hippocampal synaptic function.
