Impaired experience-dependent plasticity in barrel cortex of mice lacking the alpha and delta isoforms of CREB

The transcription factor cyclic-AMP response element binding protein (CREB) has been implicated in long-term plasticity processes in vertebrate and in vertebrate species. In the absence of the alpha/delta CREB isoforms, perfor mance is impaired in long-term memory tasks and the long-term maintenance o f long-term potentiation (LTP) is impaired in the hippocampus. However, it is not known whether CREB plays a role in neocortical plasticity. Antibodie s to CREB revealed that CREB-immunoreactive nuclei are present in all corti cal layers but are more numerous in layers II/III, where they composed at l east two thirds the total population of cells. CREB-immunopositive cells we re therefore present and densest in the very cortical layers that exhibit e xperience dependent plasticity at this age. In order to assess the role of CREB in neocortical plasticity, we studied the effect of vibrissae deprivat ion on receptive field plasticity in the barrel cortex of mutant mice lacki ng the alpha/delta isoforms of CREB. A single vibrissa was spared and the o thers removed for 18 days. In wild-types this caused potentiation of the sp ared vibrissa response. However, in adult mutants (> 6 months) spared vibri ssa responses from homozygotes were potentiated less than in any adolescent animals or in adult wild-type littermates. Surround receptive field respon ses were abnormally large in homozygotes and failed to increase by the same amount as they did in wild-types. In contrast, the alpha/delta CREB mutati on had no discernible effect on plasticity in cortical layers II/III of the younger adolescent age group (1-2 months), suggesting that different plast icity processes may operate at this age. Further tests showed that the beta isoform of CREB was up-regulated in the barrel cortex of the alpha/delta C REB knock-outs, suggesting that this subunit may have compensated partly fo r the loss of the alpha/delta isoforms, These studies suggests that CREB pl ays a role in experience-dependent plasticity in the adult neocortex.