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Volume 17, Number 8, Issue of April 15, 1997 pp. 2876-2885
Copyright ©1997 Society for Neuroscience

Selective Alteration of Long-Term Potentiation-Induced Transcriptional Response in Hippocampus of Aged, Memory-Impaired Rats

Received Oct. 9, 1996; revised Jan. 17, 1997; accepted Jan. 31, 1997.

Anthony Lanahan¹, Gregory Lyford¹, Gail S. Stevenson⁵, Paul F. Worley^{1, 2}, and Carol A. Barnes^{3, 4, 5}

Departments of ¹ Neuroscience and ² Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205-2185, and Departments of ³ Psychology and ⁴ Neurology, and ⁵ Division of Neural Systems, Memory and Aging, University of Arizona, Tucson, Arizona 85424

Normal human aging is associated with selective changes in cognition that are attributable, in part, to dysfunction of hippocampal pathways. Rodents also exhibit age-dependent hippocampal dysfunction that results in spatial memory deficits and a correlated reduction in the maintenance of long-term potentiation (LTP). Although suprathreshold stimulus protocols result in normal LTP induction in aged rats, the ability to sustain this increase in synaptic efficacy is reduced in the old animals. The maintenance phase of LTP is known to be dependent on rapid, transcriptional events, and recent studies have identified signal transduction mechanisms that link glutamate-induced responses at the synapse with transcriptional responses at the nucleus. To examine the integrity of these signaling pathways in aged hippocampus, we monitored the induction of a panel of immediate early genes (IEGs) that are known to be transcriptionally activated after LTP-inducing stimuli, using a "reverse Northern" strategy. Here we report that a broad representation of IEGs are similarly induced in awake, behaving young adult and aged, memory-impaired rats. This indicates a general preservation of these presumptive signaling pathways during the aging process. Induced levels of c-fos mRNA, however, are significantly higher in the aged animals. These observations suggest that age-dependent hippocampal dysfunction may be associated with a selective change in the dynamic activity of signaling pathways upstream of c-fos, possibly involving calcium regulation.

Key words: long-term potentiation (LTP); immediate early gene; aging; reverse Northern; age-dependent memory decline; transcription; protein synthesis inhibitor

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