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Cereb Cortex. 2014 Aug;24(8):2093-107. doi: 10.1093/cercor/bht060. Epub 2013 Mar 10.

The GABAergic septohippocampal pathway is directly involved in internal processes related to operant reward learning.

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Division of Neurosciences, Pablo de Olavide University, Seville E-41013, Spain.
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.
Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, USA.
Unité d'Etude du Movement, Hôpital Erasme-ULB, Bruxelles 1070, Belgium.
Division of Neurosciences, Pablo de Olavide University, Seville E-41013, Spain


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.


GABA; glutamate decarboxylase; hippocampus; mice; self-stimulation

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