Viral-mediated expression of a constitutively active form of cAMP response element binding protein in the dentate gyrus increases long term synaptic plasticity

Abstract

The transcription factor cAMP response element binding protein (CREB) is a key player in synaptic plasticity and learning. Phosphorylation of CREB induced by neuronal activity leads to gene transcription, a process thought to contribute to memory formation. We have previously reported that increasing CREB activity in glutamatergic CA1 pyramidal neurons or in dentate gyrus (DG) granule cells is sufficient to enhance hippocampal-dependent memory formation. This enhancement correlates with an increase in CA1 glutamatergic synaptic plasticity. However, the effects of increasing CREB activity on DG glutamatergic plasticity have not been investigated. To address this issue, we boosted CREB-dependent transcription in DG granule cells in vivo via viral mediated expression of a constitutively active form of CREB (CREBCA). Using in vitro extracellular field recordings of infected slices, we observed an increase in long-term potentiation (LTP) while short-term plasticity and basic synaptic transmission remained unaffected. These data demonstrate that boosting CREB activity in DG granule cells is sufficient to enhance LTP and suggest that this enhancement participates in the formation of better memories.