Distinct trafficking and expression mechanisms underlie LTP and LTD of NMDA receptor‐mediated synaptic responses

Abstract

Although an increasing number of studies have demonstrated the plasticity of NMDA receptor-mediated synaptic transmission, little is known about the molecular mechanisms that underlie this neurologically important process. In a study of NMDAR-mediated synaptic responses in hippocampal Schaffer-CA1 synapses whose AMPA receptor (AMPAR) activity is totally blocked, we uncovered differences between the trafficking mechanisms that underlie the long-term potentiation (LTP) and long-term depression (LTD) that can be induced in these cells under these conditions. The LTP-producing protocol failed to induce a change in the amplitude of NMDAR-mediated postsynaptic currents (NMDAR EPSCs) in the first 5-10 min, but induced gradual enhancement of NMDAR EPSCs thereafter that soon reached a stable magnitude. This "slow" LTP of NMDAR EPSCs (LTP(NMDA)) was blocked by inhibiting exocytosis or actin polymerization in postsynaptic cells. By contrast, LTD of NMDAR EPSCs (LTD(NMDA)) was immediately inducible, and, although it was blocked by the actin stabilizer, it was unaffected by exocytosis or endocytosis inhibitors. Furthermore, concomitant changes in the decay time of NMDAR EPSCs suggested that differential switches in NR2 subunit composition accompanied LTP(NMDA) and LTD(NMDA), and these changes were blocked by the calcium buffer BAPTA or an mGluR antagonist. Our results suggest that LTP(NMDA) and LTD(NMDA) utilize different NMDAR trafficking pathways and express different ratios of NMDAR subunits on the postsynaptic surface.

The Restoration After Repetitive Transcranial Magnetic Stimulation Treatment on Cognitive Ability of Vascular Dementia Rats and Its Impacts on Synaptic Plasticity in Hippocampal CA1 Area

“…NR1 subunit has the full functionality of NMDA receptor properties (Behe et al 1995). Activation of NMDAR1 has an important role in the LTP induction related to synaptic plasticity and the ability of spatial cognitive (MacDonald et al 2006;Peng et al 2009;Rebola et al 2009). Tisen (Tsien et al 1996) knocked out NMDAR NR1 gene in mice hippocampus CA1 area by using the method of gene knockout then found the loss of LTP in CA1 area after the mutation of mice, and the space exploration ability of the mutation mice in the water maze test was worse than that of the mice in normal control group significantly.…”

Interfering with the Actin Network and Its Effect on Long-Term Potentiation and Synaptic Tagging in Hippocampal CA1 Neurons in SlicesIn Vitro

“…Thus, it is feasible that the actin network guarantees the molecular/morphological basis for a tag-related housekeeping process, on top of which other key molecules like CaMKII or MAPK are only able to exert their action in synapses specifically marked either for LTP or LTD processes. Furthermore, the actin network could be involved in the PRP capture process itself by providing a distinct geometry for interactions of the kinases with the PRPs such as sculpting active synaptic zones or the whole synaptic spine, guaranteeing, for example, the activation or transport of PRPs into the spine or the transport of new AMPA-receptors to maintain LTP (Fukazawa et al, 2003;Lisman, 2003;Chen et al, 2007;Shoji-Kasai et al, 2007;Yang et al, 2008;Peng et al, 2009). Alternatively, actin filament formation could also be locally involved in PRP synthesis.…”

Fear Memory

“…Roger Nicoll and his collaborators (367) (132,237,495,682). Recently, AMPA receptor movements were actually visualized in both dendritic spines and shafts by following the GluR1 subunit (28,682).…”

“…AMPA receptor trafficking consists of lateral displacements (253), exocytosis (495,565), and/or capture by the postsynaptic density protein PSD95 (593,683). Aging, in which memory deficits are known to take place, has been suggested to involve defective trafficking of AMPA or other receptors (GABA, NMDA) (237).…”