LTP leads to rapid surface expression of NMDA but not AMPA receptors in adult rat CA1

Abstract

In the CA1 region of the rat hippocampus, long-term potentiation (LTP) requires the activation of NMDA receptors (NMDARs) and leads to an enhancement of AMPA receptor (AMPAR) function. In neonatal hippocampus, this increase in synaptic strength seems to be mediated by delivery of AMPARs to the synapse. Here we studied changes in surface expression of native AMPA and NMDA receptors following induction of LTP in the adult rat brain. In contrast to early postnatal rats, we find that LTP in the adult rat does not alter membrane association of AMPARs. Instead, LTP leads to rapid surface expression of NMDARs in a PKC- and Src-family-dependent manner. The present study suggests a developmental shift in the LTP-dependent trafficking of AMPA receptors. Moreover, our results indicate that insertion of NMDA receptors may be a key step in regulating synaptic plasticity.

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).…”

“…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.…”

“…NR2B subunits are known to be rapidly internalized in immature neurons (Roche et al, 2001). Activity-dependent trafficking of synaptic NR2B-containing receptors has been shown anatomically using in vitro fluorescent preparations (Rao and Craig, 1997), electrophysiologically (Tovar and Westbrook, 2002), and biochemically (Grosshans et al, 2002). While none of these methods or our EM-ICC have examined single synapse over time, a decrease consistent across a large population of synapses supports the idea that there is a mechanism for NR2B subunits to be trafficked out of the D-APV treated synapses.…”

Bidirectional Trafficking of Prostaglandin E2Receptors Involved in Long-Term Potentiation in Visual Cortex

“…6C). This may be because of the difficulty in detecting a small change in this value, ascribable to the rapid and constitutive cycling between intracellular stores and the membrane, or to lateral movement, as suggested in previous reports (Grosshans et al, 2002;Adesnik et al, 2005). Because LTP in hippocampus was reported to be associated with the phosphorylation of intracellular domains of glutamate receptors by protein kinases, we examined whether PGE 2 -associated LTP may involve this mechanism.…”

Differential Reelin-Induced Enhancement of NMDA and AMPA Receptor Activity in the Adult Hippocampus

“…Alternatively, increased NMDAR currents may be partly attributable to increased NMDAR trafficking to postsynaptic sites, as happens during certain forms of synaptic activity (Lan et al, 2001;Grosshans et al, 2002;Chung et al, 2004). Similarly, increased AMPAR responses after reelin application may result from enhanced single-channel activity through phosphorylation of specific Ser/Thr or tyrosine residues (Barria et al, 1997;Banke et al, 2000;Lee et al, 2000;Hayashi and Huganir, 2004) or from increased AMPAR trafficking to the synaptic sites (Shi et al, 1999;Hayashi et al, 2000;Man et al, 2003).…”