, 1995 and Liao et al , 1995) However, was this increased postsy

, 1995 and Liao et al., 1995). However, was this increased postsynaptic sensitivity due to the regulation Selisistat cell line of individual receptor function, such as ion channel conductance and open probability, or could it be due to changes in the number of receptors at synapses? Dogma from the neuromuscular junction suggested that receptors at synapses are very stable with minimal dynamic regulation (Sanes and Lichtman, 1999). However, in the late 1990s it was found that AMPAR membrane trafficking was dynamic and could be modified by long-term and short-term changes in neuronal activity.

Physiological studies using compounds such as botulinum toxin and inhibitors of the NSF protein that regulate membrane trafficking were some of the first studies to suggest that membrane trafficking of receptors was dynamic and that dynamic trafficking was important for the expression of LTP and LTD (Lledo et al., 1998 and Lüscher et al., 1999).

In addition, Fasudil immunolabeling of synapses in culture demonstrated that there were “morphological silent synapses” that contained NMDA receptors but did not have AMPARs, indicating that synapses could vary in their levels of AMPARs (Gomperts et al., 1998, Liao et al., 2001, Liao et al., 1999 and Takumi et al., 1999). Studies in culture first demonstrated directly the dynamic rapid trafficking of AMPARs. Treatment of cultures with glutamate or NMDA, a method to chemically induce LTD (Kameyama et al., 1998), resulted in the rapid endocytosis of AMPARs (Beattie et al., 2000, Carroll et al.,

1999 and Ehlers, 2000). Treatment of cultures with AMPA also induced rapid endocytosis. Interestingly, AMPARs could be differentially sorted in endosomal compartments and were in some cases rapidly recycled back into the plasma membrane and sometimes targeted to lysosomes for degradation (Figure 2). The differential sorting and recycling of AMPARs is now a major area of research and may have important ramifications on synaptic transmission and plasticity. These results indicate that dynamic rapid trafficking of receptors to Dichloromethane dehalogenase and from the synapse could play a critical role in the steady state level of receptors at synapses to regulate synaptic strength. The role of AMPAR membrane trafficking in LTP and LTD was directly visualized in 1999 using GFP-tagged receptors expressed in organotypic hippocampal slices using Sindbis virus (Shi et al., 1999). Using this novel system it was shown that GFP-GluA1 was recruited to synaptic spines after LTP induction and this recruitment paralleled synaptic strengthening (Hayashi et al., 2000 and Shi et al., 1999). Additional studies using transfected organotypic hippocampal slices further characterized the delivery of AMPARs during LTP and LTD (see below).

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