Abstract
Brain µ-opioid receptors (MOR) mediate reward and help coping with pain, social rejection, anxiety and depression. The dorsal midline thalamus (dMT) integrates visceral/emotional signals and biases behavior towards aversive or defensive states through projections to the amygdala. While a dense MOR expression in the dMT has been described, the exact cellular and synaptic mechanisms of µ-opioidergic modulation in the dMT-amygdala circuitry remain unresolved. Here, we hypothesized that MORs are important negative modulators of dMT-amygdala excitatory networks. Using retrograde tracers and targeted channelrhodopsin expression in combination with patch-clamp electrophysiology, we found that projections of dMT neurons onto both basal amygdala principal neurons (BA PN) and central amygdala (CeL) neurons are attenuated by stimulation of somatic or synaptic MORs. Importantly, dMT efferents to the amygdala drive feedforward excitation of centromedial amygdala neurons (CeM), which is dampened by MOR activation. This downregulation of excitatory activity in dMT-amygdala networks puts the µ-opioid system in a position to ameliorate aversive or defensive behavioral states associated with stress, withdrawal, physical pain or social rejection.
Highlights
Brain μ-opioid receptors (MOR) mediate reward and help coping with pain, social rejection, anxiety and depression
As basal amygdala principal neurons (BA PN) provide considerable excitatory input to the centromedial amygdala (CeM), we investigated whether the dorsal midline thalamus (dMT) drives feedforward excitation of centromedial amygdala (CeM) neurons and found it to be downregulated by MOR activation
The activation of MORs leads to a prominent hyperpolarization and inhibition of both central amygdala (CeL)- and basal amygdala (BA)-projecting neurons in the dMT and this effect was accompanied by a reduction in membrane input resistance
Summary
Brain μ-opioid receptors (MOR) mediate reward and help coping with pain, social rejection, anxiety and depression. While a dense MOR expression in the dMT has been described, the exact cellular and synaptic mechanisms of μ-opioidergic modulation in the dMT-amygdala circuitry remain unresolved. Using retrograde tracers and targeted channelrhodopsin expression in combination with patch-clamp electrophysiology, we found that projections of dMT neurons onto both basal amygdala principal neurons (BA PN) and central amygdala (CeL) neurons are attenuated by stimulation of somatic or synaptic MORs. Importantly, dMT efferents to the amygdala drive feedforward excitation of centromedial amygdala neurons (CeM), which is dampened by MOR activation. DMT efferents to the amygdala drive feedforward excitation of centromedial amygdala neurons (CeM), which is dampened by MOR activation This downregulation of excitatory activity in dMT-amygdala networks puts the μ-opioid system in a position to ameliorate aversive or defensive behavioral states associated with stress, withdrawal, physical pain or social rejection. DMT input to the CeL was sparse as compared to BA and μ-opioidergic inhibition of synaptic transmission was significantly weaker as compared to dMT-BA synapses
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