title: Granule cells in the CA3 area.
abstract: A fundamental property of neuronal networks in Ammon's horn is that each area comprises a single glutamatergic cell population and various types of GABAergic neurons. Here we describe an exception to this rule, in the form of granule cells that reside within the CA3 area and function as glutamatergic nonprincipal cells with distinct properties. CA3 granule cells in normal, healthy rats, similarly to dentate gyrus granule cells, coexpressed calbindin and the homeobox protein Prox1. However, CA3 granule cells were located outside of the dentate gyrus, often hundreds of micrometers from the hilar border, in the lucidum and radiatum layers. CA3 granule cells were present in numbers that were comparable to the rarer GABAergic neuronal subtypes, and their somato-dendritic morphology, intrinsic properties, and perforant path inputs were similar to those of dentate gyrus granule cells. CA3 granule cell axons displayed giant mossy fiber terminals with filopodial extensions, demonstrating that not all mossy fibers originate from the dentate gyrus. Somatic paired recordings revealed that CA3 granule cells innervated CA3 pyramidal and GABAergic cells similarly to conventional mossy fiber synapses. However, CA3 granule cells were distinct in the specific organization of their GABAergic inputs. They received GABAergic synapses from cholecystokinin-expressing mossy fiber-associated cells that did not innervate the dentate granule cell layer, and these synapses demonstrated unusually strong activity-dependent endocannabinoid-mediated inhibition of GABA release. These results indicate that granule cells in the CA3 constitute a glutamatergic, nonprincipal neuronal subtype that is integrated into the CA3 synaptic network.
authors.affiliation: Department of Anatomy and Neurobiology, University of California, Irvine, Irvine, California 92697, USA. szabadicsj@koki.hu
authors.forename: János
authors.initials: J
authors.lastname: Szabadics
authors.forename: Csaba
authors.initials: C
authors.lastname: Varga
authors.forename: János
authors.initials: J
authors.lastname: Brunner
authors.forename: Kang
authors.initials: K
authors.lastname: Chen
authors.forename: Ivan
authors.initials: I
authors.lastname: Soltesz
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D056654:CA3 Region, Hippocampal / Q000166:cytology*; D064026:Calbindins; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism / Q000494:pharmacology; D002766:Cholecystokinin / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D046529:Microscopy, Electron, Transmission / Q000379:methods; D009415:Nerve Net / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000145:classification* / Q000502:physiology* / Q000648:ultrastructure; D009478:Neuropeptide Y / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013569:Synapses / Q000378:metabolism / Q000648:ultrastructure; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
chemical_list: D064026:Calbindins; D063385:Cannabinoid Receptor Modulators; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018398:Homeodomain Proteins; D009478:Neuropeptide Y; D011810:Quinoxalines; D064030:S100 Calcium Binding Protein G; D025521:Tumor Suppressor Proteins; D000098551:Prospero-Related Homeobox 1 Protein; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D005680:gamma-Aminobutyric Acid; D002766:Cholecystokinin; C013411:biocytin; D008239:Lysine