title: Redistribution of CB1 cannabinoid receptors during evolution of cholinergic basal forebrain territories and their cortical projection areas: a comparison between the gray mouse lemur (Microcebus murinus, primates) and rat.
abstract: Endocannabinoid signaling, mediated by presynaptic CB1 cannabinoid receptors on neurons, is fundamental for the maintenance of synaptic plasticity by modulating neurotransmitter release from axon terminals. In the rodent basal forebrain, CB1 cannabinoid receptor-like immunoreactivity is only harbored by a subpopulation of cholinergic projection neurons. However, endocannabinoid control of cholinergic output from the substantia innominata, coincident target innervation of cholinergic and CB1 cannabinoid receptor-containing afferents, and cholinergic regulation of endocannabinoid synthesis in the hippocampus suggest a significant cholinergic-endocannabinergic interplay. Given the functional importance of the cholinergic modulation of endocannabinoid signaling, here we studied CB1 cannabinoid receptor distribution in cholinergic basal forebrain territories and their cortical projection areas in a prosimian primate, the gray mouse lemur. Perisomatic CB1 cannabinoid receptor immunoreactivity was unequivocally present in non-cholinergic neurons of the olfactory tubercule, and in cholecystokinin-containing interneurons in layers 2/3 of the neocortex. Significantly, CB1 cannabinoid receptor-like immunoreactivity was localized to cholinergic perikarya in the magnocellular basal nucleus. However, cortical cholinergic terminals lacked detectable CB1 cannabinoid receptor levels. A dichotomy of CB1 cannabinoid receptor distribution in frontal (suprasylvian) and parietotemporal (subsylvian) cortices was apparent. In the frontal cortex, CB1 cannabinoid receptor-containing axons concentrated in layers 2/3 and layer 6, while layer 4 and layer 5 were essentially devoid of CB1 cannabinoid receptor immunoreactivity. In contrast, CB1 cannabinoid receptors decorated axons in all layers of the parietotemporal cortex with peak densities in layer 2 and layer 4. In the hippocampus, CB1 cannabinoid receptor-containing terminals concentrated around pyramidal cell somata and proximal dendrites in the CA1-CA3 areas, and granule cell dendrites in the molecular layer of the dentate gyrus. CB1 cannabinoid receptors frequently localized to inhibitory GABAergic terminals while leaving glutamatergic boutons unlabeled. Aging did not affect either the density or layer-specific distribution of CB1 cannabinoid receptor-immunoreactive processes. We concluded that organizing principles of CB1 cannabinoid receptor-containing neurons and their terminal fields within the basal forebrain are evolutionarily conserved between rodents and prosimian primates. In contrast, the areal expansion and cytoarchitectonic differentiation of neocortical subfields in primates is associated with differential cortical patterning of CB1 cannabinoid receptor-containing subcortical and intracortical afferents.
authors.affiliation: Laboratory of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Scheeles väg 1:A1, Karolinska Institutet, S-17177 Stockholm, Sweden. Tibor.Harkany@mbb.ki.se
authors.forename: T
authors.initials: T
authors.lastname: Harkany
authors.forename: M B
authors.initials: MB
authors.lastname: Dobszay
authors.forename: F
authors.initials: F
authors.lastname: Cayetanot
authors.forename: W
authors.initials: W
authors.lastname: Härtig
authors.forename: T
authors.initials: T
authors.lastname: Siegemund
authors.forename: F
authors.initials: F
authors.lastname: Aujard
authors.forename: K
authors.initials: K
authors.lastname: Mackie
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001391:Azo Compounds / Q000378:metabolism; D005075:Biological Evolution; D002452:Cell Count / Q000379:methods; D016565:Cheirogaleidae; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D005455:Fluorescent Antibody Technique / Q000379:methods; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal / Q000379:methods; D009281:Naphthalenes; D009434:Neural Pathways / Q000166:cytology*; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D012844:Sincalide / Q000378:metabolism; D050496:Vesicular Glutamate Transport Proteins / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism
chemical_list: D001391:Azo Compounds; D009281:Naphthalenes; D016900:Neurofilament Proteins; D010320:Parvalbumins; D043884:Receptor, Cannabinoid, CB1; D050496:Vesicular Glutamate Transport Proteins; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; C493406:vesicular GABA transporter; D012701:Serotonin; C016118:Sudan Black B; D002795:Choline O-Acetyltransferase; D012844:Sincalide; D000109:Acetylcholine