Activity level-dependent synapse-specific AMPA receptor trafficking regulates transmission kinetics.
Central glutamatergic synapses may express AMPA-sensitive glutamate receptors (AMPA-Rs) with distinct gating properties and exhibit different transmission dynamics, which are important for computing various synaptic inputs received at different populations of synapses. However, how glutamatergic synapses acquire AMPA-Rs with distinct kinetics to influence synaptic integration remains poorly understood. Here I report synapse-specific trafficking of distinct AMPA-Rs in rat cortical layer 4 stellate and layer 5 pyramidal neurons. The analysis indicates that in single layer 4 stellate neurons thalamocortical synapses generate faster synaptic responses than intracortical synapses. Moreover, GluR1-containing AMPA-Rs traffic selectively into intracortical synapses, and this process requires sensory experience-dependent activity and slows down transmission kinetics. GluR4-containing AMPA-Rs traffic more heavily into thalamocortical synapses than intracortical synapses, and this process requires spontaneous synaptic activity and speeds up transmission kinetics. GluR2-containing AMPA-Rs traffic equally into both thalamocortical and intracortical synapses, and this process requires no synaptic activity and resets transmission kinetics. Notably, synaptic trafficking of distinct AMPA-Rs differentially regulates synaptic integration. Thus, synapse-specific AMPA-R trafficking coarsely sets and synaptic activity finely tunes transmission kinetics and integration properties at different synapses in central neurons.
Zhu
J Julius
JJ
Departments of Pharmacology and Neuroscience, University of Virginia School of Medicine, Charlottesville, Virginia 22908, USA. jjzhu@virginia.edu
D000818:Animals; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D015870:Gene Expression; D008839:Microelectrodes; D010812:Physical Stimulation; D021381:Protein Transport; D017966:Pyramidal Cells / Q000378:metabolism*; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*; D014738:Vibrissae / Q000502:physiology
D018091:Receptors, AMPA; C104724:glutamate receptor ionotropic, AMPA 4; C104722:glutamate receptor ionotropic, AMPA 2