Journal
NEUROSCIENCE
Volume 131, Issue 3, Pages 647-659Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2004.10.044
Keywords
negative cell cycle regulator; LTP; antisense oligonucleotide
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Funding
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA012848, R01DA009444, R01DA013471] Funding Source: NIH RePORTER
- NIDA NIH HHS [DA09444, DA13471, DA12848] Funding Source: Medline
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Tob (transducer of ErbB2) is a negative cell cycle regulator with anti-proliferative activity in the periphery. Using a behavioral screening paradigm to look for novel gene functions in the brain, we identified Tob as a brain-expressed protein involved in learning and memory. Behavioral training of fear-conditioning triggered a transient elevation of Tob protein, which preceded the formation of long-term memory. Functional perturbation of Tob by intra-CA1 infusion of antisense oligonucleotides in rats impaired spatial learning and memory in the Morris water maze and long-term memory for contextual fear conditioning, two behavioral paradigms that require the hippocampus. Furthermore, long-term potentiation was suppressed by Tob antisense infusion into the CA1 region. Together, these results indicate that the negative cell cycle regulator Tob is a multifunctional protein involved in hippocampus-dependent learning and memory. (c) 2005 IBRO. Published by Elsevier Ltd. All rights reserved.
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