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Posttraining infusion of cholinergic drugs into the ventral subiculum modulated memory in an inhibitory avoidance task: Interaction with the bed nucleus of the stria terminalis
Authors:Tzu-Lan Liu  KC Liang
Institution:1. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;2. Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;3. Neurobiology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;4. Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;5. Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;1. Department of Biomedical Magnetic Resonance, University of Tübingen, Germany;2. Department of Anatomy, University of Tübingen, Germany;3. Clinic for Psychiatry and Psychotherapy, University of Tübingen, Germany;4. Max-Planck-Institute for Biological Cybernetics, University of Tübingen, Germany;1. Institute of Physiology, Pécs University Medical School, Pécs, Hungary;2. Molecular Neurophysiology Research Group, Pécs University, Szentágothai Research Center, Pécs, Hungary;1. Department of Biomedical Sciences, Section of Neuroscience and Clinical Pharmacology, University of Cagliari, Cagliari, Italy;2. Centre of Excellence for the Neurobiology of Addictions, University of Cagliari, Cagliari, Italy;3. Institute of Neuroscience, National Research Council, Cagliari Section, University of Cagliari, Cagliari, Italy;4. Department of Biomedical Sciences, Neuro-Endocrine-Fluorescence (NEF) Laboratory, Cagliari, Italy;1. Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, United States;2. Department of Psychology and Human Development, Vanderbilt University, Nashville, TN, United States;3. Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, United States;1. Neurobiology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;2. Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;3. Neuroscience Program, Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, MO 63110, USA;4. Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA;5. Department of Neuroscience, Washington University School of Medicine, St. Louis, MO 63110, USA;6. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA;7. Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA;8. Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA;9. National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD 21224, USA;10. Program in Neuroscience, Harvard Medical School, Boston, MA 02215, USA;11. Ernest Gallo Clinic and Research Center, Department of Neurology, University of California San Francisco, Emeryville, CA, 94806, USA
Abstract:The ventral subiculum (vSUB), a hippocampal efferent target implicated in learning and stress coping, receives cholinergic input and sends glutamatergic output to the bed nucleus of the stria terminalis (BNST). This study examined the roles of vSUB muscarinic activation and its interaction with BNST N-methyl-d-aspartate and noradrenergic receptors in formation of aversive memory. Male Wistar rats with cannulae implanted into the vSUB or BNST were trained on a step-through inhibitory avoidance task. Shortly after training, they received cholinergic drugs infused into the vSUB and/or glutamatergic or noradrenergic drugs infused into the BNST. Results of the 1-day retention tests showed that intra-vSUB infusion of oxotremorine (0.01 μg) or scopolamine (0.3 or 3.0 μg) enhanced or impaired retention, respectively. Both effects were dose- and time-dependent, and 0.001 μg oxotremorine attenuated the amnesia induced by 3.0 μg scopolamine. The oxotremorine-induced memory enhancement was blocked by intra-BNST infusion of dl-2-amino-5-phosphonovaleric acid or propranolol at a dose not affecting retention; the amnesia induced by scopolamine was blunted by intra-BNST infusion of glutamate or norepinephrine at a dose with a negligible effect on retention. These data suggest that in an inhibitory avoidance task muscarinic activation of the vSUB modulated memory formation by interacting with the BNST glutamatergic and noradrenergic functions.
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