Persistence of Memory and Prion Mechanisms: A Perspective

Long‐term memory for behavioral sensitization is synapse specific and requires local protein synthesis at the activated synapse. Kausik Si next found that local protein synthesis is regulated by a neuron‐specific isoform of cytoplasmic polyadenylation element binding protein (CPEB). Aplysia CPEB protein is a regulator of protein synthesis that upregulated locally at activated synapses, and it is needed not for the initiation but for the stable maintenance of long‐term facilitation. Recently we have extended this work in two directions: 1) We found CPEB‐3 as a homolog of ApCPEB in the mammalian brain and found that CPEB‐3 is activated by Neuralized, an ubiquitin hydrolase. 2) We next found for a new class of prions in the mammalian brain, and found a completely new candidate – TIA (T‐cell intracellular antigen). TIA has classic prion properties in yeast and serves as part of the cellular response to systemic stress. TIA serves as a sex‐specific protective factor in PTSD and does so in female mice only. In my talk I will to provide an overall view of the emerging biology of functional prions and the various roles of these prions in brain and behavior.