26 Jun 2000

How are short-term memories converted to long-term memories? The process is certain to be complex, and a study in the 23 June issue of Science suggests thetranscription factor NPAS2 may play an important role, perhaps by regulating circadian rhythms.

Based on the observation in mice that the expression pattern of NPAS2 (neuronal PAS domain protein 2) maps onto the frontal association/limbic forebrain pathway (which may have a central role in memory consolidation), and evidence that the ontogeny of NPAS2 expression is temporally coincident with the ontogeny of learning and memory, Steven McKnight, Joseph Garcia, and colleagues at the University of Texas Southwestern Medical Center sought to determine the effect of altering the gene for NPAS2 in such a way as to interfere with its transcriptional activity. The altered form of NPAS2 did not have any obvious morphological or behavioral effects on the mice. In particular, the mice with the altered gene had no deficits in measures of short-term learning and memory. What distinguished these mice, however, is that they were not as good at remembering the contextual or auditory stimuli that signaled a mild electric shock after 24 hours had passed.

Pointing out that NPAS2 is most closely related to the protein, clock, which regulates circadian clocks, the authors suggest that "NPAS2 may serve to regulate the neuronal expression of a battery of genes required for the consolidation of long-term memory and/or to maintain a functional relation between multiple components of the frontal association/ limbic forebrain pathway."—Hakon Heimer