Mu-opioid and corticotropin-releasing-factor receptors show largely postsynaptic co-expression, and separate presynaptic distributions, in the mouse central amygdala and bed nucleus of the stria terminalis.
The anxiolytic effects of opiates active at the mu-opioid receptor (mu-OR) may be ascribed, in part, to suppression of neurons that are responsive to the stress-associated peptide, corticotropin releasing factor (CRF), in the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST). The corticotropin releasing factor receptor (CRFr) and mu-OR are expressed in both the CeA and BNST, but their subcellular relationship to each other is not known in either region. To address this question, we used dual electron microscopic immunolabeling of mu-OR and CRFr in the mouse lateral CeA and anterolateral BNST. Immunolabeling for each receptor was detected in the same as well as in separate somatic, dendritic and axonal profiles of neurons in each region. CRFr had a plasmalemmal or cytoplasmic distribution in many dendrites, including those co-expressing mu-OR. The co-expression of CRFr and mu-OR also was seen near excitatory-type synapses on dendritic spines. In both the CeA and BNST, over 50% of the CRFr-labeled dendritic profiles (dendrites and spines) contained immunoreactivity for the mu-OR. However, less than 25% of the dendritic profiles containing the mu-OR were labeled for CRFr in either region, suggesting that opiate activation of the mu-OR affects many neurons in addition to those responsive to CRF. The dendritic profiles containing CRFr and/or mu-OR received asymmetric, excitatory-type synapses from unlabeled or CRFr-labeled axon terminals. In contrast, the mu-OR was identified in terminals forming symmetric, inhibitory-type synapses. Thus, in both the CeA and BNST, mu-OR and CRFr have strategic locations for mediation of CRF and opioid effects on the postsynaptic excitability of single neurons, and on the respective presynaptic release of excitatory and inhibitory neurotransmitters. The commonalities in the synaptic location of both receptors in the CeA and BNST suggest that this is a fundamental cellular association of relevance to both drug addiction and stress-induced disorders.
Jaferi
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A
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 407 East 61st Street, New York, NY 10065, USA. azj2002@med.cornell.edu
Pickel
V M
VM
D000679:Amygdala / Q000166:cytology*; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission / Q000379:methods; D016253:Microscopy, Immunoelectron / Q000379:methods; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D018019:Receptors, Corticotropin-Releasing Hormone / Q000378:metabolism* / Q000648:ultrastructure; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D012686:Septal Nuclei / Q000166:cytology*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure
D018019:Receptors, Corticotropin-Releasing Hormone; D017450:Receptors, Opioid, mu