title: Projections from basal forebrain to prefrontal cortex comprise cholinergic, GABAergic and glutamatergic inputs to pyramidal cells or interneurons.
abstract: The present study was undertaken to characterize the pre- and postsynaptic constituents of the basal forebrain (BF) projection to the prefrontal cortex in the rat, and determine whether it includes glutamatergic in addition to established gamma-aminobutyric acid (GABA)ergic and cholinergic elements. BF fibres were labelled by anterograde transport using biotin dextran amine (BDA) and dual-stained for the vesicular transporter proteins (VTPs) for glutamate (VGluT), GABA (VGAT) or acetylcholine (VAChT). Viewed by fluorescence microscopy and estimated by stereology, proportions of BDA-labelled varicosities were found to be stained for VGluT2 (and not VGluT1 or 3), VGAT or VAChT (representing, respectively, approximately 15%, approximately 52% and approximately 19% within the infralimbic cortex). Each type was present in all, though commonly most densely in deep, cortical layers. Material was triple-stained for postsynaptic proteins to examine whether BDA+VTP+ varicosities might form excitatory or inhibitory synapses, respectively, labelled by postsynaptic density-95 kDA (PSD-95) or gephyrin (Geph). Viewed by confocal microscopy, a majority of BDA+/VGluT2+ varicosities were found to be apposed to PSD-95+ elements, and a majority of BDA+/VGAT+ varicosities to be apposed to Geph+ elements. Other series were triple-stained for cell marker proteins to assess whether the varicosities contacted interneurons or pyramidal cells. Viewed by confocal microscopy, BDA-labelled VGluT2+, VGAT+ and VAChT+ BF terminals were all found in contact with calbindin+ interneurons, whereas VGAT+ BF terminals were also seen in contact with parvalbumin+ interneurons and non-phosphorylated neurofilament+ pyramidal cells. Through distinct glutamatergic, GABAergic and cholinergic projections, the BF can thus influence cortical activity in a diverse manner.
authors.affiliation: Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4.
authors.forename: Pablo
authors.initials: P
authors.lastname: Henny
authors.forename: Barbara E
authors.initials: BE
authors.lastname: Jones
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D020532:Basal Nucleus of Meynert / Q000378:metabolism* / Q000648:ultrastructure; D015415:Biomarkers / Q000378:metabolism; D001710:Biotin / Q000031:analogs & derivatives; D001931:Brain Mapping; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D003911:Dextrans; D000076122:Disks Large Homolog 4 Protein; D005455:Fluorescent Antibody Technique; D018698:Glutamic Acid / Q000378:metabolism; D007395:Interneurons / Q000378:metabolism* / Q000648:ultrastructure; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D009434:Neural Pathways / Q000378:metabolism / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000378:metabolism*; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000648:ultrastructure; D017966:Pyramidal Cells / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D020318:Rats, Long-Evans; D013570:Synaptic Membranes / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D003911:Dextrans; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D018377:Neurotransmitter Agents; C076397:biotinylated dextran amine; C073441:gephyrin; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D001710:Biotin; D000109:Acetylcholine