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Biol. Bull. 207: 159. (October 2004)
© 2004 Marine Biological Laboratory


Abstract

Memory Enhancement by Bryostatin in Hermissenda

Andrew B. Scioletti1, Alan M. Kuzirian1, Herman T. Epstein1, Thomas J. Nelson2 and Daniel L. Alkon2

1 Marine Biological Laboratory, Woods Hole, Massachusetts
2 Blanchette Rockefeller Neuroscience Institute, Johns Hopkins University, Rockville, Maryland

Memory acquisition and information and behavioral recall are fundamental processes of great interest. Studies are being conducted in many model systems including marine molluscs like Aplysia californica and Hermissenda crassicornis.

Recently, the anti-cancer drug bryostatin has been found to enhance memory recall in rodent systems. Bryostatin is known to activate autophosphorylation of protein kinase-C (PKC), an enzyme implicated in memory formation. In Hermissenda, phosphorylated PKC activates calexcitin, a GTP/Ca2+-binding protein that triggers calcium release from internal stores while concurrently inhibiting two voltage-dependent outward K+ currents. The rise in internal Ca2+ coupled with a decrease in K+ currents is putatively responsible for the enhanced long-lasting depolarization (LLD) shown in Hermissenda type B-cell photoreceptors to be associated with memory acquisition.

Hermissenda can be trained and tested using a Pavlovian conditioning regime of light (CS) paired with agitation (US) (paired training event, TE). Previous studies have shown that two TEs produced short-term memory (STM) lasting 7 min. Nine TEs produced long-term memory (LTM; present at 60 min and lasting one day) that ultimately led to consolidated LTM (CLTM; present at 220 min and lasting up to 6 days). In this study, experimental animals exposed to low bryostatin concentrations (0.1–0.25 ng/ml) and two TEs (that normally evoke only STM) demonstrated the enhanced memory stage of LTM. Both four and six TEs (that normally do not generate LTM) tested positively for CLTM with bryostatin added. Nine TEs coupled with bryostatin at a high concentration (1.0 ng/ml), however, down-regulated memory acquisition; and the animals exhibited no conditioned response with CS testing. These findings will help elucidate knowledge about memory acquisition, storage, and retrieval; contribute information that can be used to answer fundamental questions pertaining to education and more effective teaching methods; and mediate memory-related pathologies like Alzheimer’s disease and other forms of dementia.




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A. M. Kuzirian, H. T. Epstein, C. J. Gagliardi, T. J. Nelson, M. Sakakibara, C. Taylor, A. B. Scioletti, and D. L. Alkon
Bryostatin Enhancement of Memory in Hermissenda
Biol. Bull., June 1, 2006; 210(3): 201 - 214.
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