Rapid, experience-dependent expression of synaptic NMDA receptors in visual cortex in vivo

Abstract

Sensory experience is crucial in the refinement of synaptic connections in the brain during development. It has been suggested that some forms of experience-dependent synaptic plasticity in vivo are associated with changes in the complement of postsynaptic glutamate receptors, although direct evidence has been lacking. Here we show that visual experience triggers the rapid synaptic insertion of new NMDA receptors in visual cortex. The new receptors have a higher proportion of NR2A subunits and, as a consequence, different functional properties. This effect of experience requires NMDA receptor activation and protein synthesis. Thus, rapid regulation of postsynaptic glutamate receptors is one mechanism for developmental plasticity in the brain. Changes in NMDA receptor expression provide a mechanism by which brief sensory experience can regulate the properties of NMDA receptor-dependent plasticity in visual cortex.

In vivo blockade of N-methyl-d-aspartate receptors induces rapid trafficking of NR2B subunits away from synapses and out of spines and terminals in adult cortex

“…It is not surprising that our results differ from the above mentioned and other physiological findings that may have overlooked the changes in silent synapses (e.g. see ref Quinlan et al, 1999) or the biochemical measurements that, like our light microscopic analyses, examines changes that are averaged over larger volumes (Rao and Craig, 1997;Williams et al, 1998;Grosshans et al, 2002).…”

“…Our findings predict that 30-120 min of NMDA receptor blockade could cause increases of NR2A-containing receptors, resulting in overall shortening of NMDA receptor current. Electrophysiological studies are needed to clarify whether sensitivity to ifenprodil, the antagonist selective for heteromers containing NR2B subunits, decreases after 30 min of NMDA receptor blockade by D-APV. There are studies, besides ours, showing that NR2A and NR2B subunits are regulated differently (Williams et al, 1998;Quinlan et al, 1999;Barria and Malinow, 2002). How might this subunit-specific trafficking be achieved?…”

“…Malenka and Nicoll, 1999). In vitro and fewer in vivo preparations have been used to demonstrate that NMDA receptors, too, are removed from or inserted into synaptic membrane (Rao and Craig, 1997;Liao et al, 1999;Quinlan et al, 1999;Heynen et al, 2000;Barria and Malinow, 2002;Grosshans et al, 2002;Tovar and Westbrook, 2002). However, since nearly all of these studies have used neonatal tissues, whether or not such dynamic properties of NMDA receptor subunits persist at mature synapses, in vivo, is a topic that remains relatively unexplored.…”

Development of NMDA R1 expression in chicken auditory brainstem

“…Near the end of the critical period, there is a gradual increase in the contribution of NR2A subunits in parallel with changes in NMDAR-mediated currents. These processes can be rapidly modulated by environmental stimuli (Quinlan et al, 1999b;Berardi et al, 2000).…”

“…Near the end of the critical period, there is a gradual increase in the contribution of NR2A subunits in parallel with changes in NMDAR-mediated currents. These processes can be rapidly modulated by environmental stimuli (Quinlan et al, 1999b;Berardi et al, 2000).NR1 expression increases in early development, then falls to and/or remains at an intermediate level into adulthood in rat (Akazawa et al, 1994) and mouse (Watanabe et al, 1992) as well as in chick auditory brainstem . NR2 subunits also show developmental changes in their expression.…”