CaMKII mediates input-specific early odor preference learning in rats

Abstract

The synaptic tagging hypothesis explains how input specificity is preserved in long-term potentiation of synapses. This phenomenon requires new proteins that are synthesized in the nuclei and shipped cell wide, to be captured by a tag at synapses that signal a prior synaptic activity. One specific molecule called calcium/calmodulin Kinase II (CaMKII) plays a major role and has been postulated to function as a synaptic tag due to its unique properties. The behavioral relevance of synaptic tagging has not been extensively studied. Using an early odor-preference learning model, which occurs in a week-old rat pup when a novel odor is paired with a reward, we tested the hypothesis that CaMKII activation is critical for short and long-term memories as well as for inputspecificity of the odor learning. Using behavioral pharmacology, we first tested whether blocking CaMKII with KN-62 infusion in the olfactory bulb blocks short-term (tested at 3 hr) and long-term memories (tested at 24 hr). Our results show that both memories were blocked. To test the role of CaMKII in input specificity of long-term memory, we used a PKA agonist, Sp-cAMP, to induce 24 hr memory and tested whether blocking CaMKII at the same time affects memories for the learned odor (peppermint) as well as a control odor (vanillin). Co-infusion of Sp-cAMP with KN-62 did not impair 24 hr memory for peppermint; however, the input specificity was lost since animals also showed preference to vanillin. Immunohistochemistry results show that phosphorylated CaMKII is primarily expressed in mitral cell dendrites of olfactory bulbs. These experiments help us understand the specific role of CaMKII in short and long-term odor memories, its role as a synaptic tag, and its role in memory specificity.