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Prefrontal afferents to the dorsal raphe nucleus in the rat
Authors:Luciano Gonçalves  Maria Inês Nogueira  Sara Joyce Shammah-Lagnado  Martin Metzger
Institution:1. Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, Brazil;2. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, Brazil;1. Institut für Integrative Neuroanatomie, Charité—Universitätsmedizin Berlin, Philippstrasse 12, D-10115 Berlin, Germany;2. Medizinische Klinik mit Schwerpunkt Kardiologie und Angiologie, Charité—Universitätsmedizin Berlin, Charitéplatz 1, D-10117 Berlin, Germany;3. Center for Stroke Research Berlin (CSB), Charité—Universitätsmedizin Berlin Charitéplatz 1, D-10117 Berlin, Germany;1. Computation and Neural Systems, California Institute of Technology, Pasadena, CA 91125, USA;2. Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA;1. Department of Anesthesia and Critical Care Medicine, Division of Stress Neurobiology, The Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania;2. Department of Neuroscience, Thomas Jefferson University, Farber Institute for Neurosciences, Philadelphia, Pennsylvania;1. Columbia University, Departments of Neuroscience and Psychiatry, 1051 Riverside Drive, Unit 87, New York, NY 10032, United States;2. The New York State Psychiatric Institute, Division of Integrative Neuroscience, New York, NY 10032, United States;3. Barnard College, Biology Department, 3009 Broadway, New York, NY 10027, United States;1. Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, PR China;2. Departments of Psychiatry and Psychology & Neuroscience, Dalhousie University, Halifax, Nova Scotia, B3H 2E2, Canada
Abstract:The prefrontal cortex (PFC) receives strong inputs from monoaminergic cell groups in the brainstem and also sends projections to these nuclei. Recent evidence suggests that the PFC exerts a powerful top-down control over the dorsal raphe nucleus (DR) and that it may be involved in the actions of pharmaceutical drugs and drugs of abuse. In the light of these findings, the precise origin of prefrontal inputs to DR was presently investigated by using the cholera toxin subunit b (CTb) as retrograde tracer. All the injections placed in DR produced retrograde labeling in the medial, orbital, and lateral divisions of the PFC as well as in the medial part of the frontal polar cortex. The labeling was primarily located in layer V. Remarkably, labeling in the medial PFC was denser in its ventral part (infralimbic and ventral prelimbic cortices) than in its dorsal part (dorsal prelimbic, anterior cingulate and medial precentral cortices). After injections in the rostral or caudal DR, the largest number of labeled neurons was observed in the medial PFC, whereas after injections in the mid-rostrocaudal DR, the labeled neurons were more homogeneously distributed in the three main PFC divisions. A cluster of labeled neurons also was observed around the apex of the rostral pole of the accumbens, especially after rostral and mid-rostrocaudal DR injections. Overall, these results confirm the existence of robust prefrontal projections to DR, mainly derived from the ventral part of the medial PFC, and underscore a substantial contribution of the frontal polar cortex.
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