Viral-mediated expression of a constitutively active form of CREB in hippocampal neurons increases memory

Synaptic activity-dependent phosphorylation of the transcription factor cAMP response element binding protein (CREB) leads to CREB-dependent gene transcription, a process thought to underlie long-term hippocampal synaptic plasticity and memory formation. We previously reported that increasing CREB activity in glutamatergic neurons enhances synaptic plasticity and neuronal excitability. Whether these modifications are sufficient to promote hippocampal-dependent memory formation was not determined. Here, we provide direct evidence that a brief increase in CREB-dependent transcription in either CA1 or DG neurons, using in vivo viral vectors, is sufficient to boost memory for contextual representations, as tested in the contextual fear conditioning task, without affecting motor, pain, or anxiety behaviors.