title: Enkephalin Disinhibits Mu Opioid Receptor-Rich Striatal Patches via Delta Opioid Receptors.
abstract: Opioid neuropeptides and their receptors are evolutionarily conserved neuromodulatory systems that profoundly influence behavior. In dorsal striatum, which expresses the endogenous opioid enkephalin, patches (or striosomes) are limbic-associated subcompartments enriched in mu opioid receptors. The functional implications of opioid signaling in dorsal striatum and the circuit elements in patches regulated by enkephalin are unclear. Here, we examined how patch output is modulated by enkephalin and identified the underlying circuit mechanisms. We found that patches are relatively devoid of parvalbumin-expressing interneurons and exist as self-contained inhibitory microcircuits. Enkephalin suppresses inhibition onto striatal projection neurons selectively in patches, thereby disinhibiting their firing in response to cortical input. The majority of this neuromodulation is mediated by delta, not mu-opioid, receptors, acting specifically on intra-striatal collateral axons of striatopallidal neurons. These results suggest that enkephalin gates limbic information flow in dorsal striatum, acting via a patch-specific function for delta opioid receptors.
authors.affiliation: Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, 220 Longwood Ave, Boston, MA, 02115, USA.
authors.forename: Matthew Ryan
authors.initials: MR
authors.lastname: Banghart
authors.affiliation: Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, 220 Longwood Ave, Boston, MA, 02115, USA.
authors.forename: Shay Quentin
authors.initials: SQ
authors.lastname: Neufeld
authors.affiliation: Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, 220 Longwood Ave, Boston, MA, 02115, USA.
authors.forename: Nicole Christine
authors.initials: NC
authors.lastname: Wong
authors.affiliation: Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, 220 Longwood Ave, Boston, MA, 02115, USA. Electronic address: Bernardo_Sabatini@hms.harvard.edu.
authors.forename: Bernardo Luis
authors.initials: BL
authors.lastname: Sabatini
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004745:Enkephalins / Q000494:pharmacology*; D005260:Female; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017465:Receptors, Opioid, delta / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology*
chemical_list: D004745:Enkephalins; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu