μ-Opioid Receptor-Mediated Inhibition of Intercalated Neurons and Effect on Synaptic Transmission to the Central Amygdala.

Blaesse P
Goedecke L
Bazelot M
Capogna M
Pape HC
Jüngling K

Opioids are a class of drugs active in the nervous system. Opioids made in the brain are released in a brain region called amygdala when pain occurs. However, the underlying mechanisms of opioid action in amygdala are unknown. We found that activation of opioid receptors dampens the excitability of so-called GABAergic intercalated cells (ITCs), leading to global changes in amygdala excitability.

Scientific Abstract

The amygdala is a key region for the processing of information underlying fear, anxiety, and fear extinction. Within the local neuronal networks of the amygdala, a population of inhibitory, intercalated neurons (ITCs) modulates the flow of information among various nuclei of amygdala, including the basal nucleus (BA) and the centromedial nucleus (CeM) of the amygdala. These ITCs have been shown to be important during fear extinction and are target of a variety of neurotransmitters and neuropeptides. Here we provide evidence that the activation of μ-opioid receptors (MORs) by the specific agonist DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]-Enkephalin) hyperpolarizes medially located ITCs (mITCs) in acute brain slices of mice. Moreover, we use whole-cell patch-clamp recordings in combination with local electrical stimulation or glutamate uncaging to analyze the effect of MOR activation on local microcircuits. We show that the GABAergic transmission between mITCs and CeM neurons is attenuated by DAMGO, whereas the glutamatergic transmission on CeM neurons and mITCs is unaffected. Furthermore, MOR activation induced by theta burst stimulation in BA suppresses plastic changes of feedforward inhibitory transmission onto CeM neurons as revealed by the MOR antagonist CTAP d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2. In summary, the mITCs constitute a target for the opioid system, and therefore, the activation of MOR in ITCs might play a central role in the modulation of the information processing between the basolateral complex of the amygdala and central nuclei of the amygdala.

μ-Opioid Receptor-Mediated Inhibition of Intercalated Neurons and Effect on Synaptic Transmission to the Central Amygdala.
Activation of mu opioid receptors (MORs) hyperpolarizes medial intercalated cells (mITCs) of the amygdala. A, Localization of dorsal and ventral clusters of mITCs [mITC(d) and mITC(v)] in the amygdala of a transgenic GAD67-eGFP mouse. Interneurons were identified by their green fluorescence. Cell nuclei are stained blue. Current-clamp recordings were performed in both mITC(d)s and mITC(v)s. B, Example recording of a mITC showing a significant hyperpolarization in response to application of the MOR agonist DAMGO; the hyperpolarization was accompanied by drop in input resistance as assessed by injection of an hyperpolarizing current pulse.
Citation
2015.J. Neurosci., 35(19):7317-25.
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