All Title Author
Keywords Abstract

Differential trafficking of AMPA receptors following activation of NMDA receptors and mGluRs

DOI: 10.1186/1756-6606-4-30

Keywords: Synaptic plasticity, long-term depression, DHPG, GluA2, NMDA, mGluR, super ecliptic phluorin

Full-Text   Cite this paper   Add to My Lib


AMPA receptor trafficking is under exquisite control in excitatory neurons (reviewed in [1,2]). One way to change the efficacy of a synapse is to redistribute AMPA receptors at the postsynaptic membrane so as to either increase or decrease their number and thus alter the responsiveness of the synapse to glutamate. Such changes in synaptic efficacy, termed synaptic plasticity, are crucial for normal brain function, particularly during the development of synaptic connections and memory formation. One form of plasticity, long term depression (LTD), involves a decrease in synaptic strength and can occur via trafficking of AMPA receptors away from synapses. Two major forms of LTD have been described in the CNS that are triggered by the activation of NMDA and mGluRs. These are induced physiologically by trains of electrical stimulation [3-5] but can also be mimicked by the application of specific agonists, in particular N-methyl D-aspartate (NMDA) [6,7] and dihydroxyphenylglycine DHPG [8-10], respectively.For NMDA-induced LTD there is agreement between electrophysiological and imaging studies on the importance of AMPA receptor endocytosis in LTD expression [1,3,11,12]. In the case of mGluR-induced LTD (mGluR-LTD), however, conflicting evidence has been reported [13]. Immunofluorescence and biochemical studies indicate that surface AMPA receptor numbers decrease on exposure to DHPG [14-16]. However, a range of electrophysiological measurements, such as changes in paired-pulse facilitation [14,17-20], failure rate [17], coefficient of variation [14,17] and mEPSC parameters [14,17], are more indicative of a presynaptic locus of expression. Consistent with this, recordings from adult hippocampal slices show no change in postsynaptic sensitivity to glutamate following DHPG-induced LTD [21] and in both adult and juvenile hippocampal slices the amount of stimulus-induced zinc exocytosis (a measure of neurotransmitter release) decreases as a result of DHPG-induced LTD [22]. A dev


comments powered by Disqus