It is widely accepted that activation of the NMDA-type glutamate receptor (NMDAR) is required for experience-dependent strengthening and weakening of visual cortical synaptic connections. This plasticity occurs predominantly during a critical period of visual cortex development when visual receptive fields are being formed and refined. Some forms of NMDAR-mediated plasticity may be strictly confined to developmental time points. Other forms are sensitive to experience, where brief periods of sensory deprivation can alter the mechanisms as well as the capacity for NMDAR-dependent plasticity. Recent evidence suggests that presynaptic NMDARs may have a unique role in this refinement, yet the developmental and experience-dependent regulation of presynaptic NMDARs have not been studied. To understand the role that presynaptic NMDARs have in visual receptive field refinement, we need to study their effects on synaptic plasticity during development and with altered visual experience. We will use electrophysiology and immuno-electron microscopy on mice at different stages of visual system development, raised with or without visual experience, to test three hypotheses formed by our preliminary findings. 1) There is a developmental decrease in the functional expression of presynaptic NMDARs, which increases glutamate release early in development. 2) The contribution of presynaptic NMDARs to release probability changes after visual deprivation in the adult, but dark rearing at younger stages does not. 3) These developmental and experience-dependent changes modify the properties of spike timing-dependent synaptic depression. There is a consensus that NMDARs are required for many types of plasticity in the visual system, but the mechanisms and limitations of this plasticity continue to be disputed. Our study will examine the possibility that the conflicting data on the role of NMDARs in plasticity may be explained by developmental differences in the expression of experience-dependent plasticity. Elucidating the involvement of pre- versus postsynaptic NMDARs in synaptic plasticity will provide insights into the eventual treatment of amblyopia and other conditions caused by the improper development of synaptic connections. ? ? ?
| Larsen, Rylan S; Smith, Ikuko T; Miriyala, Jayalakshmi et al. (2014) Synapse-specific control of experience-dependent plasticity by presynaptic NMDA receptors. Neuron 83:879-93 |
| Larsen, Rylan S; Corlew, Rebekah J; Henson, Maile A et al. (2011) NR3A-containing NMDARs promote neurotransmitter release and spike timing-dependent plasticity. Nat Neurosci 14:338-44 |
| Corlew, Rebekah; Brasier, Daniel J; Feldman, Daniel E et al. (2008) Presynaptic NMDA receptors: newly appreciated roles in cortical synaptic function and plasticity. Neuroscientist 14:609-25 |
