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Cytokine Responses to LTP Induction in the Rat Hippocampus: A Comparison of In Vitro and In Vivo Techniques

Jankowsky, Joanna L. and Derrick, Brian E. and Patterson, Paul H. (2000) Cytokine Responses to LTP Induction in the Rat Hippocampus: A Comparison of In Vitro and In Vivo Techniques. Learning and Memory, 7 (6). pp. 400-412. ISSN 1072-0502. PMCID PMC311345. doi:10.1101/lm.32600.

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Because exogenous application of a number of cytokines and growth factors can alter synaptic properties, we sought to determine if endogenous cytokine expression is affected by neuronal activity. In addition, we examined whether cytokine expression is altered by the techniques used to stimulate and record from hippocampal neurons. Using semi-quantitative RNase protection and RT-PCR assays, we studied the expression of 18 cytokine, growth factor, and receptor genes in the hippocampus following the induction of Schaffer collateral-CA1 long-term potentiation (LTP). We found that various cytokines are dramatically induced following preparation of slices for in vitro recording and as a result of injury following acute electrode placement in vivo. These increases can be overcome in vivo, however, using permanent electrodes implanted three weeks prior to testing. Using this chronic preparation, we found that interleukin-6 (IL-6) mRNA was upregulated nearly 20-fold by LTP induction in vivo, marking the first demonstration of endogenous regulation of this cytokine in response to LTP. In situ hybridization for IL-6 revealed that upregulation is tightly localized near the site of stimulation and is detected only in non-neuronal cells, identified as GFAP+ astrocytes and GFAP− cells within proximal blood vessels. Coupled with previous results showing that exogenously applied IL-6 can prevent the induction of LTP, this finding suggests a mechanism by which the local release of a cytokine could regulate LTP at nearby sites.

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Additional Information:© 2000 Cold Spring Harbor Laboratory Press. The Authors acknowledge that six months after the full-issue publication date, the Article will be distributed under a Creative Commons CC-BY-NC License (Attribution-NonCommercial 4.0 International License, Received April 17, 2000; accepted in revised form August 25, 2000. The authors thank Erin Schuman and members of the Schuman lab, especially Hannah Dvorak, Gerald Reis, Lixin Tang, and David Kantor, for help with in vitro electrophysiology. We acknowledge Rachel Grimes, Desiree Villarreal, and Cyndy Davis for technical assistance with in vivo experiments. We are also grateful to Lisa Banner, Herman Govan, and Kai Zinn for tireless advice on establishing the RNA assays, and to Doreen McDowell, Bill Lease, and Jesse Flores for continued laboratory support. We thank Erin Schuman and Andy Groves for helpful comments on the manuscript. This work was supported by NIH (National Institutes of Health) grants NS20916 to P.H.P., GM08194 to B.E.D., DA11983 to B.E.D., and by National Research Service Award training grant 5 T32 GM 07737 (J.L.J.). The publication costs of this article were defrayed in part by payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 USC section 1734 solely to indicate this fact.
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NIH5 T32 GM 07737
Issue or Number:6
PubMed Central ID:PMC311345
Record Number:CaltechAUTHORS:20160210-163940896
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Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:64399
Deposited By: George Porter
Deposited On:19 Feb 2016 19:36
Last Modified:10 Nov 2021 23:30

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