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The Journal of Neuroscience, September 2, 2009, 29(35):10883-10889; doi:10.1523/JNEUROSCI.2594-09.2009

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Development/Plasticity/Repair
NGF Is Essential for Hippocampal Plasticity and Learning

James M. Conner,^1 * Kevin M. Franks,^2,3 * Andrea K. Titterness,^6 * Kyle Russell,⁶ David A. Merrill,¹ Brian R. Christie,^6,7 Terrence J. Sejnowski,^2,3,4 and Mark H. Tuszynski^1,5

Departments of ¹Neurosciences and ²Biology, University of California, San Diego, La Jolla, California 92093, ³Computational Neurobiology Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, ⁴Howard Hughes Medical Institute, ⁵Veterans Administration Medical Center, San Diego, California 92161, ⁶Neuroscience Program, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada, and ⁷Division of Medical Sciences, University of Victoria, Victoria, British Columbia V8W 2Y2, Canada

Correspondence should be addressed to Mark H. Tuszynski, Department of Neurosciences 0626, University of California, San Diego, La Jolla, CA 92093. Email: mtuszynski{at}ucsd.edu

Nerve growth factor (NGF) is produced in the hippocampus throughout life and is retrogradely trafficked to septal cholinergic neurons, providing a potential mechanism for modulating cholinergic inputs and, thereby, hippocampal plasticity. To explore NGF modulation of hippocampal plasticity and function, NGF levels were augmented or blocked in intact adult rats, and subsequent in vivo effects on cholinergic neurons, hippocampal long-term potentiation (LTP), and learning were examined. NGF augmentation significantly enhanced cholinergic neuronal markers and facilitated induction of hippocampal LTP. Blockade of endogenous NGF significantly reduced hippocampal LTP and impaired retention of spatial memory. These findings reveal an essential role for NGF in regulating biological mechanisms related to plasticity and memory in the intact adult brain.

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Received May 29, 2009; revised July 21, 2009; accepted July 22, 2009.

Correspondence should be addressed to Mark H. Tuszynski, Department of Neurosciences 0626, University of California, San Diego, La Jolla, CA 92093. Email: mtuszynski{at}ucsd.edu

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