Cytokine responses to LTP induction in the rat hippocampus: A comparison of in vitro and in vivo techniques

Because exogenous application of a number of cytokines and growth factors c an alter synaptic properties, we sought to determine if endogenous cytokine expression is affected by neuronal activity. In addition, we examined whet her cytokine expression is altered by the techniques used to stimulate and record from hippocampal neurons. Using semi-quantitative RNase protection a nd RT-PCR assays, we studied the expression of 18 cytokine, growth factor, and receptor genes in the hippocampus following the induction of Schaffer c ollateral-CA1 long-term potentiation (LTP). We found that various cytokines are dramatically induced following preparation of slices for in vitro reco rding and as a result of injury following acute electrode placement in vivo . These increases can be overcome in vivo, however, using permanent electro des implanted three weeks prior to testing. Using this chronic preparation, eve found that interleukin-6 (IL-6) mRNA was upregulated nearly 20-fold by LTP induction in vivo, marking the first demonstration of endogenous regul ation of this cytokine in response to LTP. In situ hybridization for IL-6 r evealed 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 resul ts showing that exogeneously 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.