RECENT BEHAVIORAL HISTORY MODIFIES COUPLING BETWEEN NEURONAL ACTIVITY AND IMMEDIATE-EARLY GENE TRANSCRIPTION IN HIPPOCAMPAL AND NEOCORTICAL NEURONS

T. Miyashita¹*; L. Maes¹; B.L. McNaughton²;
P.F. Worley³; C.A. Barnes²; J.F. Guzowski¹

1. Neurosci, Univ New Mexico, Albuquerque, NM, USA
2. NSMA, Univ Arizona, Tucson, AZ, USA
3. Neurosci & Neurol, Johns Hopkins Univ, Baltimore, MD, USA

Previously, we have shown that after nine 5-min exposures to a single environmental context, each separated by 25 min, the percentage of CA1 neurons transcribing the plasticity-related immediate-early gene (IEG) Arc decreased dramatically as compared to a 1st or even 2nd exposure. By contrast, no differences could be detected in the firing properties of CA1 neurons in this "massed" exposure paradigm. These findings indicate that the coupling between neural activity and experience-dependent gene expression, which we have termed electro-transcriptional coupling (ETC), is a plastic process. Here, we investigate further the nature of ETC by asking three major questions: 1) how many behavioral repetitions is needed for de-coupling of neural activity and IEG transcription?; 2) how much time is required for IEG transcription mechanisms to "re-set"; and 3) does transcription of other IEGs exhibit this same experience-dependent plasticity? In rats exposed to the same environment 4 times (30 min apart), 9 times (30 min apart), and 9 times (60 min apart), transcription of the IEGs Arc and zif268 was dramatically reduced in CA3, CA1, and neocortical neurons, as compared to rats exposed once to the environment or twice (4 hours apart). These findings indicate that 4 repeated exposures is sufficient to modify ETC for both Arc and zif268. Furthermore, the decreased IEG induction in animals with 60 min inter-exposure interval indicates that ETC does not "re-set" even after 1 hr after experience. The present experiment helps define further the parameters governing ETC, although further experiments will be needed to determine the molecular and cellular mechanisms of this plastic process.

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