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Transplanted septal neurons make viable cholinergic synapses with a host hippocampus
Authors:Menahem Segal  Anders Bjorklund  Fred H Gage
Institution:1. Isotope Department, The Weizmann Institute of Science, 76100 Rehovot Israel;2. Department of Histology, University of Lund, Lund Sweden;1. Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA;2. Neuroscience, Yale University School of Medicine, New Haven, CT 06520, USA;3. Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA;4. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA;5. Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA;6. Department of Computer Science, Yale University, New Haven, CT 06520, USA;7. Department of Statistics and Data Science, Yale University, New Haven, CT 06520, USA;8. Department of Biomedical Informatics & Data Science, Yale University, New Haven, CT 06520, USA;9. Keck Microarray Shared Resource, Yale University School of Medicine, New Haven, CT 06520, USA;10. Department of Neurosurgery, Mayo Clinic, Jacksonville, FL 32224, USA;11. Department of Neurology, Children’s Hospital of Fudan University, Shanghai 201102, China;1. Department of Psychiatry, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada;1. Department of Neuroscience and Carney Institute for Brain Sciences, Brown University, Providence, RI, USA;2. Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA, USA;3. Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
Abstract:Cell suspensions from the fetal septal region were injected stereotaxically into the hippocampus of fornix-fimbria-transected adult rats. The host rats were sacrificed up to 3 months after the operation and the hippocampus sliced into 350 microns transverse slices. Intracellular recording was made from CA1 neurons adjacent to the graft. Electrical stimulation of the graft produced a voltage-dependent depolarization in some recorded neurons. This was associated with an increase in spontaneous and anodal break action potential discharges. In addition, a slow after-hyperpolarization (AHP) which typically follows a burst discharge was blocked during the depolarization indicating that the stimulation may block a Ca2+-dependent K+ current. The effects of the stimulation were antagonized by atropine. A response to the stimulation was seen 2 weeks but not 1 week after grafting. Over time, cells that were located away from the graft became activated by the stimulation. This was correlated with the extent of proliferation of acetylcholinesterase-containing fibers around the graft. These results suggest that grafted septal neurons make viable cholinergic connections with a host hippocampus.
Keywords:acetylcholine  transplantation  septum  hippocampus
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