Poster Session 1 - B5
1,2,3Sammy Cai, 1,2Graham L. Collingridge, 1,3Zhengping Jia
1. Dept. of Physiology, University of Toronto; 2. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital; 3. Neurosciences & Mental health, The Hospital for Sick Children
Long-term potentiation (LTP) has been studied extensively to understand the molecular mechanisms underlying learning and memory. The NMDA receptor-dependent form of LTP can be characterized into protein kinase A (PKA)-dependent and independent forms depending on the spacing between theta burst stimuli (TBS). Compressed (c)TBS does not require PKA whereas spaced (s)TBS elicits a PKA-dependent form that requires the insertion of calcium permeable AMPA receptors (CP-AMPAR) (Park et al [2016] J Neurosci.). The PKA-dependent form of LTP has implications in protein translation that may alter the molecular composition, structure, and function of synapses; however, the mechanism by which synapses integrate the timing of stimuli remains elusive. To investigate these processes, we have used electrophysiology to compare cTBS and sTBS at mouse CA1 synapses using genetic knockout (KO) or pharmacological inhibition of the PKA pathway. We found that LTP induced by sTBS was sensitive to inhibitors of PKA and protein synthesis. Mice lacking LIM kinase-1 (LIMK1), a potent regulator of actin cytoskeleton dynamics, revealed deficits in PKA-dependent LTP, and was insensitive to protein synthesis inhibitors applied throughout sTBS. Preliminary results suggest that PKA can activate LIMK1 to trigger protein synthesis-dependent pathways critical for plasticity. These findings provide insight into how spaced stimuli can be consolidated into long-term memories.