Two of the canonical requirements for long lasting synaptic plasticity and learning and memory are CREB-dependent transcription, and activity dependent alterations in protein expression. MicroRNA-132 (miR132) is a CREB-regulated miRNA that is induced by neuronal activity and neurotrophins, and plays a role in regulating neuronal morphology and cellular excitability by suppressing the translation of multiple mRNAs. Little is known about the role of miR132 in learning and memory in vivo and the effects of miR132 expression on synaptic function.

The data presented in this thesis demonstrate that miRI32 is rapidly induced in vivo by pharmacological stimulation and by behaviorally relevant stimuli that induce memory formation. We also show that overexpression of miR132 increases the paired-pulse ratio and decreases synaptic depression in cultured hippocampal neurons without affecting the size of either excitatory synaptic currents or the readily releasable pool of synaptic vesicles. These findings are the first to demonstrate that microRNAs can regulate short-term plasticity in neurons.