Ž . Molecular Brain Research 60 1998 50–56 Research report Synaptic activity-dependent modulation of mitochondrial gene expression in the rat hippocampus Joanna M. Williams a,1 , Vida L. Thompson a , Sara E. Mason-Parker b , Wickliffe C. Abraham b , Warren P. Tate a, ) a Department of Biochemistry and Centre for Gene Research, UniÕersity of Otago, P.O. Box 56, Dunedin, New Zealand b Department of Psychology, UniÕersity of Otago, P.O. Box 56, Dunedin, New Zealand Accepted 7 July 1998 Abstract Ž . In order to identify genes that may underlie the maintenance of long-term potentiation LTP at perforant path synapses, complementary DNA libraries were synthesised from dentate gyrus total RNA extracts prepared 48 h after the induction of LTP and from control dentate gyrus extracts. Through differential screening of the LTP library we have identified the mitochondrial 12S rRNA Ž . mt12SrRNA as a transcript that was elevated at this late time. Northern blot analyses showed that the elevation in mt12SrRNA expression began around 8 h and persisted for at least 2 weeks post-tetanus. We then examined the expression patterns of other mitochondrially-encoded genes and demonstrated a similar elevation in their expression. mt12SrRNA levels were also elevated in other hippocampal regions, including areas CA3 and CA1 and were elevated following low-frequency stimulation or in the presence of an N-methyl-D-aspartate receptor antagonist where induction of LTP was precluded. Taken together, these observations suggest that a long-lasting up-regulation of energy production may be triggered by synaptic activity and this activity need not be of sufficient strength to induce LTP, but may be related to the induction of a metaplastic state. q 1998 Elsevier Science B.V. All rights reserved. Keywords: Mitochondria; Long-term potentiation; Memory 1. Introduction Long-lasting changes in synaptic efficacy can be brought about by patterned stimulation in a variety of excitatory pathways in the brain. The persistence of one form of Ž . synaptic plasticity, long-term potentiation LTP , has been extensively studied at perforant path synapses in the hip- pocampus. Here the LTP, although decremental, can last w x for several weeks or months 2,7,9,23 . The associated converse phenomenon, heterosynaptic long-term depres- Ž . wx sion LTD , is also long-lasting 3 . The persistence of such synaptic modifications may be maintained through the expression of plasticity-associated genes. Previously we have demonstrated a strong correlation between persis- tent LTP and the increased expression of two specific ) Corresponding author. Fax: q 64-3-479-7866; E-mail: warren.tate@stonebow.otago.ac.nz 1 To whom reprints should be addressed: Department of Biochemistry, University of Otago, P.O. Box 56, Dunedin, New Zealand. Ž . immediate early genes IEGs zif r 268 and krox20 w x 2,24,31 . The Zifr268 and Krox20 proteins are both members of the zinc finger transcription factor family and as such may trigger a cascade of molecular events that are responsible for the long-term changes associated with this persistent form of neural activity. What classes of gene products might be needed to maintain synaptic plasticity in a neuron? Structural changes at the synapses may contribute to synaptic plasticity and may be brought about by molecular remodelling of synap- tic and cytoskeletal proteins resulting in the synapses becoming more responsive to subsequent neurotransmitter release. Indeed elevation in the expression of NR2A and w x NR2B subunits 32 and their phosphorylation have been w x observed 25,26 . Neurons in the hippocampus also seem to be particularly sensitive to their energy status, such that brief deprivation of oxygen can lead to delayed neuronal wx death 1 . Changes in energy metabolism can be observed w x following LTP-induction 30 , and more recently mito- chondria have been directly linked via Ca 2q homeostasis w x to post-tetanic potentiation 28 . These observations sug- 0169-328Xr98r$ - see front matter q 1998 Elsevier Science B.V. All rights reserved. Ž . PII: S0169-328X 98 00165-X