Impaired synaptic plasticity and cAMP response element-binding protein activation in Ca2+/calmodulin-dependent protein kinase type IV/Gr-deficient mice

The Ca2+/calmodulin-dependent protein kinase type IV/Gr (CaMKIV/Gr) is a ke y effector of neuronal Ca2+ signaling; its function was analyzed by targete d gene disruption in mice. CaMKIV/Gr-deficient mice exhibited impaired neur onal cAMP-responsive element binding protein (CREB) phosphorylation and Ca2 +/CREB-dependent gene expression. They were also deficient in two forms of synaptic plasticity: long-term potentiation (LTP) in hippocampal CA1 neuron s and a late phase of long-term depression in cerebellar Purkinje neurons. However, despite impaired LTP and CREB activation, CaMKIV/Gr-deficient mice exhibited no obvious deficits in spatial learning and memory. These result s support an important role for CaMKIV/Gr in Ca2+-regulated neuronal gene t ranscription and synaptic plasticity and suggest that the contribution of o ther signaling pathways may spare spatial memory of CaMKIV/Gr-deficient mic e.