Smolen et al. Title: How Can Memories Last for Days, Years, or a Lifetime? Proposed Mechanisms for Maintaining Synaptic Potentiation and Memory Authors: Paul Smolen, Douglas A. Baxter, and John H. Byrne Laboratory of Origin: Department of Neurobiology and Anatomy W. M. Keck Center for the Neurobiology of Learning and Memory McGovern Medical School of the University of Texas Health Science Center at Houston Houston, Texas 77030 Running Title: Proposed Mechanisms to Maintain LTP and Memory Correspondence Address: Paul D. Smolen Department of Neurobiology and Anatomy W.M. Keck Center for the Neurobiology of Learning and Memory McGovern Medical School of the University of Texas Health Science Center at Houston Houston, TX 77030 E-mail:
[email protected] Vo ice: (713) 500-5601 FAX: (713) 500-0623 1 Smolen et al. Abstract With memory encoding reliant on persistent changes in the properties of synapses, a key question is how can memories be maintained from days to months or a lifetime given molecular turnover? It is likely that positive feedback loops are necessary to persistently maintain the strength of synapses that participate in encoding. Such feedback may occur within signal-transduction cascades and/or the regulation of translation, and it may occur within specific subcellular compartments or within neuronal networks. Not surprisingly, numerous positive feedback loops have been proposed. Some posited loops operate at the level of biochemical signal transduction cascades, such as persistent activation of Ca2+/calmodulin kinase II (CaMKII) or protein kinase M ζ. Another level consists of feedback loops involving transcriptional, epigenetic and translational pathways, and autocrine actions of growth factors such as BDNF.