ABSTRACT
Changes in visual cortical responses that are induced by monocular visual deprivation are a widely studied example of competitive, experience-dependent neural plasticity. It has been thought that the deprived-eye pathway will fail to compete against the open-eye pathway for limited amounts of brain-derived neurotrophic factor, which acts on TrkB and is needed to sustain effective synaptic connections. We tested this model by using a chemical-genetic approach in mice to inhibit TrkB kinase activity rapidly and specifically during the induction of cortical plasticity in vivo. Contrary to the model, TrkB kinase activity was not required for any of the effects of monocular deprivation. When the deprived eye was re-opened during the critical period, cortical responses to it recovered. This recovery was blocked by TrkB inhibition. These findings suggest a more conventional trophic role for TrkB signaling in the enhancement of responses or growth of new connections, rather than a role in competition.
Subject(s)
Receptor, trkB/metabolism , Sensory Deprivation/physiology , Vision, Monocular/physiology , Visual Cortex/metabolism , Visual Pathways/physiology , Amino Acid Substitution , Animals , Brain-Derived Neurotrophic Factor/metabolism , Functional Laterality/physiology , Mice , Mice, Mutant Strains , Neural Inhibition/physiology , Neuronal Plasticity/physiology , Receptor, trkB/genetics , Recovery of Function/physiologyABSTRACT
Experience is a powerful sculptor of developing neural connections. In the primary visual cortex (V1), cortical connections are particularly susceptible to the effects of sensory manipulation during a postnatal critical period. At the molecular level, this activity-dependent plasticity requires the transformation of synaptic depolarization into changes in synaptic weight. The molecule alpha calcium-calmodulin kinase type II (alphaCaMKII) is known to play a central role in this transformation. Importantly, alphaCaMKII function is modulated by autophosphorylation, which promotes Ca(2+)-independent kinase activity. Here we show that mice possessing a mutant form of alphaCaMKII that is unable to autophosphorylate show impairments in ocular dominance plasticity. These results confirm the importance of alphaCaMKII in visual cortical plasticity and suggest that synaptic changes induced by monocular deprivation are stored specifically in glutamatergic synapses made onto excitatory neurons.
