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Excitatory Synaptic Transmission Is Differentially Modulated by Opioid Receptors along the Claustrocingulate Pathway
Jacob M Reeves1,2, Erwin Arias-Hervert2, Gracianne E Kmiec2
1Neuroscience Graduate Program, University of Michigan, Ann Arbor, Michigan 48109.
Eneuro
|July 16, 2025
Summary
Opioid receptors (Kappa, Mu, and Delta) modulate pain and emotion circuits. This study reveals Kappa opioid receptors uniquely inhibit direct claustrum-to-cortex neuron communication, impacting pain perception.
Area of Science:
- Neuroscience
- Neuropharmacology
- Pain Research
Background:
- The anterior cingulate cortex (ACC) and claustrum (CLA) are crucial for pain and emotion processing.
- Both regions express Kappa (KOR), Mu (MOR), and Delta (DOR) opioid receptors.
- The precise modulation of CLA-ACC circuitry by opioid receptors remains unclear.
Purpose of the Study:
- To investigate the effects of opioid receptor activation on glutamatergic signaling in the CLA→ACC circuit.
- To elucidate the distinct roles of KOR, MOR, and DOR in modulating CLA-ACC synaptic transmission.
Main Methods:
- Utilized spatial transcriptomics, brain slice electrophysiology, optogenetics, and pharmacology in mice.
- Examined synaptic transmission from CLA to Layer 5 pyramidal (L5 PYR) cells in the ACC.
- Assessed the impact of KOR, MOR, and DOR agonists on excitatory responses.
Main Results:
- KOR, MOR, and DOR agonists generally reduced excitatory synaptic transmission from CLA to ACC L5 PYR cells.
- KOR agonists uniquely reduced monosynaptic transmission, indicating a specific role in direct CLA→ACC pathways.
- MOR and DOR agonists primarily affected slower, longer-latency recurrent excitatory responses.
Conclusions:
- Opioid receptors differentially regulate the claustrocingulate circuit.
- Kappa opioid receptors play a distinct role in modulating direct CLA→ACC synaptic transmission.
- Findings offer novel insights into opioid-mediated regulation of pain and emotional processing networks.
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