Expression of mu opioid receptor in dorsal diencephalic conduction system: new insights for the medial habenula.

TitleExpression of mu opioid receptor in dorsal diencephalic conduction system: new insights for the medial habenula.
Publication TypeJournal Article
Year of Publication2014
AuthorsGardon O, Faget L, P Chung CSin, Matifas A, Massotte D, Kieffer BL
JournalNeuroscience
Volume277
Pagination595-609
Date Published2014 Sep 26
ISSN1873-7544
KeywordsAcetylcholine, Animals, Enkephalins, Female, Gene Knock-In Techniques, Habenula, Immunohistochemistry, Interpeduncular Nucleus, Luminescent Proteins, Male, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Transgenic, Neural Pathways, Neurons, Protein Precursors, Receptors, Opioid, mu, Substance P
Abstract

The habenular complex, encompassing medial (MHb) and lateral (LHb) divisions, is a highly conserved epithalamic structure involved in the dorsal diencephalic conduction system (DDC). These brain nuclei regulate information flow between the limbic forebrain and the mid- and hindbrain, integrating cognitive with emotional and sensory processes. The MHb is also one of the strongest expression sites for mu opioid receptors (MORs), which mediate analgesic and rewarding properties of opiates. At present however, anatomical distribution and function of these receptors have been poorly studied in MHb pathways. Here we took advantage of a newly generated MOR-mcherry knock-in mouse line to characterize MOR expression sites in the DDC. MOR-mcherry fluorescent signal is weak in the LHb, but strong expression is visible in the MHb, fasciculus retroflexus (fr) and interpeduncular nucleus (IPN), indicating that MOR is mainly present in the MHb-IPN pathway. MOR-mcherry cell bodies are detected both in basolateral and apical parts of MHb, where the receptor co-localizes with cholinergic and substance P (SP) neurons, respectively, representing two main MHb neuronal populations. MOR-mcherry is expressed in most MHb-SP neurons, and is present in only a subpopulation of MHb-cholinergic neurons. Intense diffuse fluorescence detected in lateral and rostral parts of the IPN further suggests that MOR-mcherry is transported to terminals of these SP and cholinergic neurons. Finally, MOR-mcherry is present in septal regions projecting to the MHb, and in neurons of the central and intermediate IPN. Together, this study describes MOR expression in several compartments of the MHb-IPN circuitry. The remarkably high MOR density in the MHb-IPN pathway suggests that these receptors are in a unique position to mediate analgesic, autonomic and reward responses.

DOI10.1016/j.neuroscience.2014.07.053
Alternate JournalNeuroscience
PubMed ID25086313
PubMed Central IDPMC4164589
Grant List16658 / / PHS HHS / United States
DA-05010 / DA / NIDA NIH HHS / United States
P50 DA005010 / DA / NIDA NIH HHS / United States
U01 AA016658 / AA / NIAAA NIH HHS / United States