title: Complementary distribution of type 1 cannabinoid receptors and vesicular glutamate transporter 3 in basal forebrain suggests input-specific retrograde signalling by cholinergic neurons.
abstract: Basal forebrain cholinergic neurons project to diverse cortical and hippocampal areas and receive reciprocal projections therefrom. Maintenance of a fine-tuned synaptic communication between pre- and postsynaptic cells in neuronal circuitries also requires feedback mechanisms to control the probability of neurotransmitter release from the presynaptic terminal. Release of endocannabinoids or glutamate from a postsynaptic neuron has been identified as a means of retrograde synaptic signalling. Presynaptic action of endocannabinoids is largely mediated by type 1 cannabinoid (CB1) receptors, while fatty-acid amide hydrolase (FAAH) is involved in inactivating some endocannabinoids postsynaptically. Alternatively, vesicular glutamate transporter 3 (VGLUT3) controls release of glutamate from postsynaptic cells. Here, we studied the distribution of CB1 receptors, FAAH and VGLUT3 in cholinergic basal forebrain nuclei of mouse and rat. Cholinergic neurons were devoid of CB1 receptor immunoreactivity. A fine CB1 receptor-immunoreactive (ir) fibre meshwork was present in medial septum, diagonal bands and nucleus basalis. In contrast, the ventral pallidum and substantia innominata received dense CB1 receptor-ir innervation and cholinergic neurons received CB1 receptor-ir presumed synaptic contacts. Consistent with CB1 receptor distribution, FAAH-ir somata were abundant in basal forebrain and appeared in contact with CB1 receptor-containing terminals. Virtually all cholinergic neurons were immunoreactive for FAAH. A significant proportion of cholinergic cells exhibited VGLUT3 immunoreactivity in medial septum, diagonal bands and nucleus basalis, and were in close apposition to VGLUT3-ir terminals. VGLUT3 immunoreactivity was largely absent in ventral pallidum and substantia innominata. We propose that specific subsets of cholinergic neurons may utilize endocannabinoids or glutamate for retrograde control of the efficacy of input synapses, and the mutually exclusive complementary distribution pattern of CB1 receptor-ir and VGLUT3-ir fibres in basal forebrain suggests segregated input-specific signalling mechanisms by cholinergic neurons.
authors: 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: Tibor
authors: T
authors: Harkany
authors: Wolfgang
authors: W
authors: Härtig
authors: Paul
authors: P
authors: Berghuis
authors: Marton B
authors: MB
authors: Dobszay
authors: Yuri
authors: Y
authors: Zilberter
authors: Robert H
authors: RH
authors: Edwards
authors: Ken
authors: K
authors: Mackie
authors: Patrik
authors: P
authors: Ernfors
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism; D026922:Amino Acid Transport Systems, Acidic / Q000378:metabolism*; D000818:Animals; D002795:Choline O-Acetyltransferase / Q000378:metabolism*; D005455:Fluorescent Antibody Technique / Q000379:methods; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal / Q000295:instrumentation / Q000379:methods; D009474:Neurons / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D015398:Signal Transduction; D012844:Sincalide / Q000378:metabolism; D013003:Somatosensory Cortex / Q000166:cytology / Q000378:metabolism; D050496:Vesicular Glutamate Transport Proteins; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D026922:Amino Acid Transport Systems, Acidic; D002795:Choline O-Acetyltransferase; D010320:Parvalbumins; D010751:Phosphopyruvate Hydratase; D043884:Receptor, Cannabinoid, CB1; D044282:Receptor, Serotonin, 5-HT1A; D012844:Sincalide; D050496:Vesicular Glutamate Transport Proteins; D000099252:Fatty Acid Amide Hydrolases; C460879:SLC17A8 protein, human