Recent behavioral history modifies coupling between cell activity and Arc gene transcription in hippocampal CA1 neurons

doi:10.1073/pnas.0505519103

Recent behavioral history modifies coupling between cell activity and Arc gene transcription in hippocampal CA1 neurons

^*Department of Neurosciences, University of New Mexico Health Sciences Center, Albuquerque, NM 87131; ^§Arizona Research Laboratories, Division of Neural Systems, Memory and Aging, and ^¶Departments of Psychology and Neurology, University of Arizona, Tucson, AZ 85724-5115; and ^∥Departments of Neuroscience and Neurology, The Johns Hopkins University, Baltimore, MD 21205

Edited by Richard L. Huganir, The Johns Hopkins University School of Medicine, Baltimore, MD, and approved November 18, 2005 (received for review June 30, 2005)

Abstract

The ability of neurons to alter their transcriptional programs in response to synaptic input is of fundamental importance to the neuroplastic mechanisms underlying learning and memory. Because of technical limitations of conventional gene detection methods, the current view of activity-dependent neural transcription derives from experiments in which neurons are assumed quiescent until a signaling stimulus is given. The present study was designed to move beyond this static model by examining how earlier episodes of neural activity influence transcription of the immediate–early gene Arc. Using a sensitive FISH method that detects primary transcript at genomic alleles, the proportion of hippocampal CA1 neurons that activate transcription of Arc RNA was constant at ≈40% in response to both a single novel exploration session and daily sessions repeated over 9 days. This proportion is similar to the percentage of active neurons defined electrophysiologically. However, this close correspondence was disrupted in rats exposed briefly, but repeatedly, to the same environment within a single day. Arc transcription in CA1 neurons declined dramatically after as few as four 5-min sessions, despite stable electrophysiological activity during all sessions. Additional experiments indicate that the decrement in Arc transcription occurred at the cellular, rather than synaptic level, and was not simply linked to habituation to novelty. Thus, the neural genomic response is governed by recent, but not remote, cell firing history in the behaving animal. This state-dependence of neuronal transcriptional coupling provides a mechanism of metaplasticity and may regulate capacity for synaptic modification in neural networks.

Footnotes

↵ ‡ To whom correspondence should be addressed. E-mail: john.g{at}uci.edu.
↵ † Present address: Department of Neurobiology and Behavior and Center for the Neurobiology of Learning and Memory, University of California, Irvine, CA 92697-3800.
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.