Long-term potentiation (LTP) in the CA1 region of the hippocampus has been the primary model by which to study the cellular and molecular basis of memory. Calcium/calmodulin-dependent protein kinase II (CaMKII) is necessary for LTP induction, is persistently activated by stimuli that elicit LTP, and can, by itself, enhance the efficacy of synaptic transmission. The analysis of CaMKII autophosphorylation and dephosphorylation indicates that this kinase could serve as a molecular switch that is capable of long-term memory storage. Consistent with such a role, mutations that prevent persistent activation of CaMKII block LTP, experience-dependent plasticity and behavioural memory. These results make CaMKII a leading candidate in the search for the molecular basis of memory.

Whole-cell recordings from optic tectal neurons in Xenopus tadpoles were used to study the maturation of a glutamatergic synapse. The first glutamatergic transmission is mediated only by N-methyl-D-aspartate (NMDA) receptors and is silent at resting potentials. More mature synapses acquire transmission by alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. This maturational program is mimicked by postsynaptic expression of constitutively active calcium-calmodulin-dependent protein kinase II (CaMKII). Newly formed synapses may be silent unless sufficient depolarization is provided by coincident activity that could activate postsynaptic CaMKII, resulting in the appearance of AMPA responses.

Previous studies suggest that neuronal activity may guide the development of synaptic connections in the central nervous system through mechanisms involving glutamate receptors and GTPase-dependent modulation of the actin cytoskeleton. Here we demonstrate by in vivo time-lapse imaging of optic tectal cells in Xenopus laevis tadpoles that enhanced visual activity driven by a light stimulus promotes dendritic arbor growth. The stimulus-induced dendritic arbor growth requires glutamate-receptor-mediated synaptic transmission, decreased RhoA activity and increased Rac and Cdc42 activity. The results delineate a role for Rho GTPases in the structural plasticity driven by visual stimulation in vivo.

No abstract

Calcium-calmodulin-dependent protein kinase II (CaMKII) promotes the maturation of retinotectal glutamatergic synapses in Xenopus. Whether CaMKII activity also controls morphological maturation of optic tectal neurons was tested using in vivo time-lapse imaging of single neurons over periods of up to 5 days. Dendritic arbor elaboration slows with maturation, in correlation with the onset of CaMKII expression. Elevating CaMKII activity in young neurons by viral expression of constitutively active CaMKII slowed dendritic growth to a rate comparable to that of mature neurons. CaMKII overexpression stabilized dendritic structure in more mature neurons, whereas CaMKII inhibition increased their dendritic growth. Thus, endogenous CaMKII activity limits dendritic growth and stabilizes dendrites, and it may act as an activity-dependent mediator of neuronal maturation.