Visual Deprivation Modifies Both Presynaptic Glutamate Release and the Composition of Perisynaptic/Extrasynaptic NMDA Receptors in Adult Visual Cortex

Abstract

Use-dependent modifications of synapses have been well described in the developing visual cortex, but the ability for experience to modify synapses in the adult visual cortex is poorly understood. We found that 10 d of late-onset visual deprivation modifies both presynaptic and postsynaptic elements at the layer 432/3 connection in the visual cortex of adult mice, and these changes differ from those observed in juveniles. Although visual deprivation in juvenile mice modifies the subunit composition and increases the current duration of synaptic NMDA receptors (NMDARs), no such effect is observed at synapses between layer 4 and layer 2/3 pyramidal neurons in adult mice. Surprisingly, visual deprivation in adult mice enhances the temporal summation of NMDAR-mediated currents induced by bursts of high-frequency stimulation. The enhanced temporal summation of NMDAR-mediated currents in deprived cortex could not be explained by a reduction in the rate of synaptic depression, because our data indicate that late-onset visual deprivation actually increases the rate of synaptic depression. Biochemical and electrophysiological evidence instead suggest that the enhanced temporal summation in adult mice could be accounted for by a change in the molecular composition of NMDARs at perisynaptic/extrasynaptic sites. Our data demonstrate that the experience-dependent modifications observed in the adult visual cortex are different from those observed during development. These differences may help to explain the unique consequences of sensory deprivation on plasticity in the developing versus mature cortex.

NR2A at CA1 Synapses Is Obligatory for the Susceptibility of Hippocampal Plasticity to Sleep Loss

“…Specific and rapid enrichment of NR2A synaptic content after SD The alteration in NMDA receptor subunit composition after sleep loss is unique in specificity, restricted subcellular localization and rapid onset compared with other examples of NMDAR regulation through experience (Quinlan et al, 2004;Yashiro et al, 2005;Chen and Bear, 2007). EM revealed that SD effects were confined to a single NMDAR subtype, provoking a selective increase of NR2A expression by 1.6-fold, while not affecting synapse size.…”

“…Experience-dependent changes in shortterm plasticity of glutamatergic synaptic transmission have been described (Finnerty et al, 1999;Yashiro et al, 2005). To study the possible impact of SD on CA3 to CA1 short-term plasticity during nearthreshold repetitive stimulation, we tracked the behavior of AMPAR-EPSCs in response to 5 Hz trains of 50 pulses (see Materials and Methods).…”

Developmental Switch in the Contribution of Presynaptic and Postsynaptic NMDA Receptors to Long-Term Depression

“…A common theme appears to be emerging that the induction mechanisms of synaptic plasticity adjust over development to adapt to ongoing changes in presynaptic and postsynaptic properties (Yasuda et al, 2003;Frenkel and Bear, 2004;Nosyreva and Huber, 2005;Yashiro et al, 2005;He et al, 2006;Jo et al, 2006). For example, there is a developmental switch in the relative presynaptic versus postsynaptic expression of metabotropic glutamate receptor-mediated LTD in the hippocampus (Nosyreva and Huber, 2005).…”

Repetitive visual stimulation enhances recovery from severe amblyopia

“…In addition, dark-exposure engages mechanisms that lower the threshold for synaptic plasticity in principle neurons (Cooper and Bear 2012), including the scaling up of AMPARs at excitatory synapses (Goel and Lee 2007) and the reactivation of endocannabinoid-dependent synaptic depression at inhibitory synapses . Dark exposure also increases the expression of NR2b-containing NMDARs, thereby enhancing the temporal summation of NMDAR-mediated synaptic currents and expanding the integration window for spike-timing dependent synaptic plasticity (Yashiro et al 2005;He et al 2006;Guo et al 2012). Indeed, the combination of chronic monocular deprivation with dark exposure appears to render the adult visual cortex hyperplastic.…”