Heterogeneity of the supramammillary–hippocampal pathways: evidence for a unique GABAergic neurotransmitter phenotype and regional differences

Authors

  • Rabia Soussi,

    1. INSERM UMR 751, Laboratoire Epilepsie et Cognition, 27 Boulevard Jean Moulin, 13385 Marseille, F-13005, France
    2. Aix-Marseille University, Faculté de Médecine Timone, 27 Boulevard Jean Moulin, 13385 Marseille, F-13005, France
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  • Nianhui Zhang,

    1. Department of Neurobiology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA
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  • Siroun Tahtakran,

    1. Department of Neurobiology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA
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  • Carolyn R. Houser,

    1. Department of Neurobiology, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA
    2. Brain Research Institute, David Geffen School of Medicine at the University of California Los Angeles, Los Angeles, CA, USA
    3. Research Service, Veterans Affairs Greater Los Angeles Healthcare System, West Los Angeles, Los Angeles, CA, USA
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  • Monique Esclapez

    1. INSERM UMR 751, Laboratoire Epilepsie et Cognition, 27 Boulevard Jean Moulin, 13385 Marseille, F-13005, France
    2. Aix-Marseille University, Faculté de Médecine Timone, 27 Boulevard Jean Moulin, 13385 Marseille, F-13005, France
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Dr Monique Esclapez, 1INSERM UMR 751, as above.
E-mail: Monique.esclapez@univmed.fr

Abstract

The supramammillary nucleus (SuM) provides substantial projections to the hippocampal formation. This hypothalamic structure is involved in the regulation of hippocampal theta rhythm and therefore the control of hippocampal-dependent cognitive functions as well as emotional behavior. A major goal of this study was to characterize the neurotransmitter identity of the SuM–hippocampal pathways. Our findings demonstrate two distinct neurochemical pathways in rat. The first pathway originates from neurons in the lateral region of the SuM and innervates the supragranular layer of the dorsal dentate gyrus and, to a much lesser extent, the ventral dentate gyrus. This pathway displays a unique dual phenotype for GABAergic and glutamatergic neurotransmission. Axon terminals contain markers of GABAergic neurotransmission, including the synthesizing enzyme of GABA, glutamate decarboxylase 65, and the vesicular GABA transporter and also a marker of glutamatergic neurotransmission, the vesicular glutamate transporter 2. The second pathway originates from neurons in the most posterior and medial part of the SuM and innervates exclusively the inner molecular layer of the ventral dentate gyrus and the CA2/CA3a pyramidal cell layer of the hippocampus. The axon terminals from the medial part of the SuM contain the vesicular glutamate transporter 2 only. These data demonstrate for the first time the heterogeneity of the SuM–hippocampal pathways, not only from an anatomical but also a neurochemical point of view. These pathways, implicated in different neuronal networks, could modulate different hippocampal activities. They are likely to be involved differently in the regulation of hippocampal theta rhythm and associated cognitive functions as well as emotional behavior.

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