Recovery of Impaired Memory: Expression of c-Fos and Egr-1 Transcription Factors during Restoration of Damaged Engram in the Chick Brain.

Abstract

Impairment of protein synthesis in the brain during learning prevents memory consolidation and results in amnesia, which until recently has been regarded irreversible. However, in some cases impaired memory could be restored by various "reminder" stimuli. The present study is based on the hypothesis that even in behaviorally profound amnesia, some disintegrated fragments of the engram are preserved in the brain and could be re-integrated into the whole system by specific types of stimuli. The aim of the present study was to test this hypothesis in an experimental model of pharmacologically induced memory impairment in young chicks and to reveal the brain areas involved in this process by mapping of reminder-induced expression of transcriptional factors c-Fos and Egr-1. We show that reminder treatment results in the recovery of memory impaired by protein synthesis inhibition during learning and induces c-Fos and Egr-1 expression in the brain regions involved in learning in this behavioral model. The patterns of c-Fos and Egr-1 induced expression in animals with impaired memory differed from the patterns of animals with unimpaired memory and as well as naïve animals with no memory. Thus, analysis of activity-induced c-Fos and Egr-1 expression revealed the brain regions that were specifically activated by the reminder treatment. At the behavioral level, this treatment led to memory recovery. Altogether, these results suggest that the reminder-induced transcriptional activity in the brain of amnestic animals occurs in regions maintaining the engram fragments that reintegrate to recover the impaired memory.