Distinct requirements for layer 4 NMDA receptors in experience-dependent visual cortical plasticity

Abstract

Purpose : Within primary visual cortex (V1), numerous forms of plasticity occur as a consequence of experience and deprivation. Examples include the shift in ocular dominance that follows monocular deprivation (MD), and the experience-dependent potentiation caused by selective visual experience to a single stimulus orientation. Testing the cortical response to visual stimulation presented to one eye at a time has revealed that these forms of plasticity are input-specific within binocular V1, implying that they occur prior to binocular integration. This psychophysical evidence suggests that modification occurs at thalamocortical synapses onto dendrites within cortical layer 4 (L4), the layer with the densest thalamocortical input. A common feature of these forms of plasticity is the requirement for NMDA-type glutamate receptor (NMDAR) activation in excitatory principal neurons of V1. We therefore hypothesized that NMDARs in L4 neurons would be necessary for NMDAR-dependent, input-specific visual cortical plasticity.

Methods : To test the requirement for L4 NMDARs in different forms of visual plasticity, we used an intersectional transgenic approach to selectively delete NMDARs from L4 principal cells. We probed for three distinct forms of plasticity in V1 of awake mice: (1) depression of deprived eye responses induced by 3 days of MD in juveniles, (2) potentiation of open eye responses induced by 1 week of MD, and (3) stimulus-specific response potentiation that follows daily exposure to the same simple visual stimulus.

Results : Depression of deprived eye responses following MD was impaired in mice lacking L4 NMDARs, as predicted. The impairment in MD-induced response depression corresponded with a sparing of visual acuity and contrast sensitivity deficits through the deprived eye, and could be explained mechanistically by the loss of long-term synaptic depression onto V1 neurons in L4 using ex vivo slice experiments. Meanwhile, we found, unexpectedly, that open-eye potentiation and stimulus-specific response potentiation both persist even when NMDARs are genetically eliminated from principal cells in L4.

Conclusions : Our findings reveal a crucial requirement for L4 NMDARs in visual cortical synaptic depression, and a surprisingly negligible role for L4 NMDARs in visual cortical response potentiation, suggesting that these forms of NMDAR-dependent plasticity occur in other cortical neuronal populations.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.