Sensory activity differentially modulates N-methyl-D-aspartate receptor subunits 2A and 2B in cortical layers

Activity-dependent modulation of N-methyl-d-aspartate (NMDA) receptors containing selective NR2 subunits has been implicated in plastic processes in developing and adult sensory cortex. Aiming to reveal differential sensitivity of NR2 subunits to sustained changes in sensory activity, we utilized four paradigms that blocked, reinstated, or initiated sensory visual activity. Laminar prevalence of N-methyl-d-aspartate receptor subunit 2A- (NR2A)- and N-methyl-d-aspartate receptor subunit 2B- (NR2B)-containing synapses in visual cortex of postnatal and adult ferrets was assessed using quantitative electron microscopy. Light-deprivation at all ages resulted in a downregulation of NR2A, while recovery from deprivation resulted in an upregulation. Furthermore, premature eyelid opening caused a precocious increase of NR2A. Thus, transitions between periods of dark and light rapidly and bidirectionally regulate NR2A, regardless of cortical layer or age. In contrast, NR2B regulation is layer- and age-dependent. Only in layer IV, NR2B prevalence displays a one-time decline about 3 weeks after the initiation of sensory activity upon normal or premature eyelid opening, or upon termination of dark-rearing. Incongruity in patterns of NR2A and NR2B modulation by activity is consistent with involvement of these subunits in two distinct, yet partially co-occurring processes: developmental plasticity with a critical period, and lifelong plasticity that is established in early developmental ages.