Experience-Dependent Equilibration of AMPAR-Mediated Synaptic Transmission during the Critical Period

Publication date: 24 January 2017
Source:Cell Reports, Volume 18, Issue 4
Author(s): Kyung-Seok Han, Samuel F. Cooke, Weifeng Xu
Experience-dependent synapse refinement is essential for functional optimization of neural circuits. However, how sensory experience sculpts excitatory synaptic transmission is poorly understood. Here, we show that despite substantial remodeling of synaptic connectivity, AMPAR-mediated synaptic transmission remains at equilibrium during the critical period in the mouse primary visual cortex. The maintenance of this equilibrium requires neurogranin (Ng), a postsynaptic calmodulin-binding protein important for synaptic plasticity. With normal visual experience, loss of Ng decreased AMPAR-positive synapse numbers, prevented AMPAR-silent synapse maturation, and increased spine elimination. Importantly, visual deprivation halted synapse loss caused by loss of Ng, revealing that Ng coordinates experience-dependent AMPAR-silent synapse conversion to AMPAR-active synapses and synapse elimination. Loss of Ng also led to sensitized long-term synaptic depression (LTD) and impaired visually guided behavior. Our synaptic interrogation reveals that experience-dependent coordination of AMPAR-silent synapse conversion and synapse elimination hinges upon Ng-dependent mechanisms for constructive synaptic refinement during the critical period.

Graphical abstract

Teaser

Han et al. find that experience-dependent elimination of glutamatergic synapses and conversion of AMPAR-silent synapses to AMPAR-positive synapses together maintain AMPAR-positive synapses at equilibrium during the critical period. Neurogranin coordinates these processes for functional optimization and experience-dependent maturation of excitatory circuits.


http://ift.tt/2ku41zj