An important role of neural activity-dependent CaMKIV signaling in the consolidation of long-term memory.

Calcium/calmodulin-dependent protein kinase IV (CaMKIV) has been implicated in the regulation of CRE-dependent transcription. To investigate the role of this kinase in neuronal plasticity and memory, we generated transgenic mice in which the expression of a dominant-negative form of CaMKIV (dnCaMKIV) is restricted to the postnatal forebrain. In these transgenic mice, activity-induced CREB phosphorylation and c-Fos expression were significantly attenuated. Hippocampal late LTP (L-LTP) was also impaired, whereas basic synaptic function and early LTP (E-LTP) were unaffected. These deficits correlated with impairments in long-term memory, specifically in its consolidation/retention phase but not in the acquisition phase. These results indicate that neural activity-dependent CaMKIV signaling in the neuronal nucleus plays an important role in the consolidation/retention of hippocampus-dependent long-term memory.