title: The GABAergic septohippocampal pathway is directly involved in internal processes related to operant reward learning.
abstract: We studied the role of γ-aminobutyric acid (GABA)ergic septohippocampal projections in medial septum (MS) self-stimulation of behaving mice. Self-stimulation was evoked in wild-type (WT) mice using instrumental conditioning procedures and in J20 mutant mice, a type of mouse with a significant deficit in GABAergic septohippocampal projections. J20 mice showed a significant modification in hippocampal activities, including a different response for input/output curves and the paired-pulse test, a larger long-term potentiation (LTP), and a delayed acquisition and lower performance in the MS self-stimulation task. LTP evoked at the CA3-CA1 synapse further decreased self-stimulation performance in J20, but not in WT, mice. MS self-stimulation evoked a decrease in the amplitude of field excitatory postsynaptic potentials (fEPSPs) at the CA3-CA1 synapse in WT, but not in J20, mice. This self-stimulation-dependent decrease in the amplitude of fEPSPs was also observed in the presence of another positive reinforcer (food collected during an operant task) and was canceled by the local administration of an antibody-inhibiting glutamate decarboxylase 65 (GAD65). LTP evoked in the GAD65Ab-treated group was also larger than in controls. The hippocampus has a different susceptibility to septal GABAergic inputs depending on ongoing cognitive processes, and the GABAergic septohippocampal pathway is involved in consummatory processes related to operant rewards.
authors.affiliation: Division of Neurosciences, Pablo de Olavide University, Seville E-41013, Spain.
authors.forename: Germán
authors.initials: G
authors.lastname: Vega-Flores
authors.affiliation: Developmental Neurobiology and Regeneration Laboratory, Institute for Research in Biomedicine, Barcelona, Spain Department of Cell Biology, University of Barcelona, Barcelona E-08028, Spain Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas (CIBERNED-ISCIII), Spain.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Rubio
authors.affiliation: Division of Neurosciences, Pablo de Olavide University, Seville E-41013, Spain.
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Jurado-Parras
authors.affiliation: Division of Neurosciences, Pablo de Olavide University, Seville E-41013, Spain.
authors.forename: María Ángeles
authors.initials: MÁ
authors.lastname: Gómez-Climent
authors.affiliation: Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, USA.
authors.forename: Christiane S
authors.initials: CS
authors.lastname: Hampe
authors.affiliation: Unité d'Etude du Movement, Hôpital Erasme-ULB, Bruxelles 1070, Belgium.
authors.forename: Mario
authors.initials: M
authors.lastname: Manto
authors.affiliation: Developmental Neurobiology and Regeneration Laboratory, Institute for Research in Biomedicine, Barcelona, Spain Department of Cell Biology, University of Barcelona, Barcelona E-08028, Spain Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas (CIBERNED-ISCIII), Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Soriano
authors.affiliation: Developmental Neurobiology and Regeneration Laboratory, Institute for Research in Biomedicine, Barcelona, Spain Department of Cell Biology, University of Barcelona, Barcelona E-08028, Spain Centro de Investigación Biomédica en Red para Enfermedades Neurodegenerativas (CIBERNED-ISCIII), Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Pascual
authors.affiliation: Division of Neurosciences, Pablo de Olavide University, Seville E-41013, Spain.
authors.forename: Agnès
authors.initials: A
authors.lastname: Gruart
authors.affiliation: Division of Neurosciences, Pablo de Olavide University, Seville E-41013, Spain jmdelgar@upo.es.
authors.forename: José M
authors.initials: JM
authors.lastname: Delgado-García
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D003216:Conditioning, Operant / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D059330:GABAergic Neurons / Q000502:physiology*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012201:Reward; D012653:Self Stimulation / Q000502:physiology; D012686:Septal Nuclei / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2
keywords: GABA; glutamate decarboxylase; hippocampus; mice; self-stimulation