A Possible Epigenetic Mechanism for the Persistence of Memory

Excerpt

Synaptic plasticity, the change in synaptic efficacy inresponse to external cues, has been shown to be one of thecritical cellular mechanisms of memory storage (Blissand Collingridge 1993; Lisman and McIntyre 2001; Morris 2003). Like behavioral memory, synaptic plasticityhas at least two temporally distinct forms: a short-termform lasting minutes and a long-term form lasting days.At the molecular level long-term synaptic plasticity differs from short-term synaptic plasticity in that it requiresthe synthesis of new mRNA and protein (Steward andSchuman 2001; Malinow and Malenka 2002; Ehlers2003) and is accompanied by the structural alteration ofpreexisting synapses and growth of new synapses (Baileyand Kandel 1993; Yuste and Bonhoeffer 2001). Eventhough it requires the synthesis of new mRNA in the nucleus and the nucleus is shared by all the synapses of agiven cell, long-term synaptic plasticity can still besynapse specific. How could a genetic program that is cellwide give rise to synapse specificity? Work in rodentsand in the marine snail Aplysia has given rise to the ideathat the synapse could be selectively marked by synapticstimulation. The synaptic marking results in either selective transport or selective utilization of plasticity-relatedmolecules only at the marked synapse (Martin et al. 1997;Frey and Morris 1998). An early attempt to characterizethe molecular nature of the synaptic mark revealed thatthere is a rapamycin-sensitive, local protein synthesis–dependent component that is needed for the long-termmaintenance of synaptic facilitation (Casadio et al. 1999)...