Formation of long-term memory without short-term memory revealed by CaMKII inhibition

Long-term memory (LTM) consolidation is thought to require the prior establishment of short-term memory (STM). Here we show that optogenetic or genetic CaMKII inhibition impairs STM for an inhibitory avoidance task at 1 h but not LTM at 1 day in mice. Similarly, cortico-amygdala synaptic potentiation was more sensitive to CaMKII inhibition at 1 h than at 1 day after training. Thus, LTM does not require the formation of STM, and CaMKII-dependent plasticity specifically regulates STM for avoidance memory. Inhibiting CaMKII impairs short-term memory (STM) in mice during an avoidance task but does not affect long-term memory (LTM). This suggests that STM and LTM are processed differently, with CaMKII critical for STM but not LTM.