Inhibition of conditioned stimulus pathway phosphoprotein 24 expression blocks the development of intermediate-term memory in Hermissenda.

Studies of memory consolidation have identified multiple phases or stages in the formation of memories. The multiple components of memory can be broadly divided into the three phases; short-term, intermediate-term, and long-term. Although molecular changes underlying short- and long-term memory have been examined extensively, the molecular mechanisms supporting the formation of intermediate-term memory are poorly understood. In several examples of cellular and synaptic plasticity, intermediate memory depends on translation but not transcription. One-trial conditioning in Hermissenda results in the development of intermediate memory that is associated with enhanced cellular excitability and the phosphorylation of a 24 kDa protein referred to as conditioned stimulus pathway phosphoprotein (Csp24). Using amino acid sequences derived from Csp24 peptide fragments, a full-length cDNA was cloned and shown to contain multiple beta-thymosin-like domains. The expression of Csp24 and the development of enhanced excitability, a characteristic of intermediate memory, were blocked by antisense oligonucleotide-mediated downregulation of Csp24 without affecting the induction of immediate enhanced excitability, a characteristic of short-term memory. These results demonstrate that the synthesis of Csp24 is required for the development and maintenance of intermediate memory.