μ-Opioid receptor activation modulates CA3-to-CA1 gamma oscillation phase-coupling

Area of Science:

• Neuroscience
• Computational Neuroscience
• Neuropharmacology

Background:

• Hippocampal area CA1 exhibits alternating low-frequency gamma oscillations (γ) phase-locked to CA3 and high-frequency γ phase-locked to the medial entorhinal cortex in vivo.
• In hippocampal slices, CA1 γ is typically phase-locked to CA3 low-frequency γ, but CA1 can generate intrinsic high-frequency γ when Schaffer collaterals are severed.

Purpose of the Study:

• To investigate whether micro-opioid receptor (MOR) modulation can control the coupling between CA1 and CA3 gamma oscillations (γ).
• To determine the role of MOR-expressing interneurons in regulating hippocampal network states.

Main Methods:

• Electrophysiological recordings of gamma oscillations (γ) in rat ventral hippocampus slices.
• Pharmacological manipulation using MOR agonist DAMGO and antagonist CTAP.
• Selective local application of DAMGO to CA1 and CA3 subregions.

Main Results:

• MOR activation by DAMGO reduced the dominant frequency of CA3 slow γ and suppressed the phase coupling of CA1 γ to CA3 γ.
• DAMGO increased the power of CA1 intrinsic fast γ, an effect blocked by the MOR antagonist CTAP.
• Local DAMGO application to CA1 reduced phase coupling, while local application to CA3 mimicked the frequency reduction but not the coupling change.

Conclusions:

• MOR-expressing CA1 interneurons, activated by Schaffer collaterals, mediate the phase coupling between CA3 and CA1 γ.
• Modulation of these interneurons by MOR agonists can switch CA1 network activity between states, potentially controlling information flow between hippocampal subfields and the entorhinal cortex.