CREB manipulations alter the properties and stability of hippocampal place cells

Location specific firing of hippocampal place cells support spatial learning and memory. Place cell maps can be both stable and flexible across repeated exposures to a familiar environment. The degree of stability is impacted by the specific task demands (e.g. presence of a motivating goal location), changing environmental cues, or simply time. Changes in place cell maps are mediated by various plasticity mechanisms. CREB is an activity dependent transcription factor that has an large role in long-term memory and synaptic & intrinsic plasticity, yet its role in place cell map stability has been understudied. Previous findings indicate that CREB activity has a bidirectional effect on learning and cell excitability. We hypothesized that overexpression of CREB in hippocampal area CA1 would increase learning rates, sharpen place cell tuning, and stabilize place cell maps. On the other hand, we predicted that expression of a CREB repressor, dominant-negative CREB (dn-CREB), would decrease learning, broaden place cell tuning, and destabilize place cell maps. To address these hypotheses, we used longitudinal two-photon calcium imaging to monitor the same cell populations in the CA1 of control, CREB, and dn-CREB mice performing a goal-oriented spatial learning task. Surprisingly, we found that overexpression of CREB reduced the fraction of place cells, while dn-CREB sharpened the tuning of place cells. Both CREB and dn-CREB expression resulted in place cell maps that were hyperstable in response to a change in reward location and slowed the initial reconfiguration of place cells towards the reward location. CREB expression reduced cell firing rates and dn-CREB increased neuronal firing These findings demonstrate that CREB levels and task features work in concert to modulate the properties and map stability of CA1 place cells.Neuroscienc