title: Remodeling of synaptic AMPA receptor subtype alters the probability and pattern of action potential firing.
abstract: Changes in the subunit composition of postsynaptic AMPA-type glutamate receptors can be induced at CNS synapses by neural activity and under certain pathological conditions. Fear-induced incorporation of GluR2-containing receptors at cerebellar synapses selectively prolongs the decay time of synaptic currents, whereas a switch from GluR2-lacking to GluR2-containing receptors induced by parallel fiber stimulation reduces the amplitude in addition to lengthening the duration of EPSCs. Although it is often assumed that these two forms of synaptic plasticity will alter action potential (AP) firing in the postsynaptic neuron, this has not been directly tested. Using a dynamic current-clamp approach, we now show that the fear-induced increase in EPSC duration increases the size of EPSPs and thereby markedly enhances the AP firing probability. In contrast, the parallel fiber stimulation-triggered switch in GluR2 expression reduces the EPSP-AP coupling because of the decrease in the synaptic current amplitude. The switch also abolished the paired-pulse facilitation that arose from an activity and spermine-dependent unblock of GluR2-lacking receptors and hence reduced the ability of paired stimuli to evoke two consecutive APs. Therefore, fear-induced incorporation of GluR2 receptors enhances the EPSP-AP coupling, but the parallel fiber stimulation-triggered switch reduces both the EPSP-AP coupling and evoked AP doublets. In contrast to long-term potentiation and depression, which modify the amplitude of synaptic currents, this activity-induced change in AMPA receptor phenotype alters synaptic conductance waveform and postsynaptic short-term plasticity. These changes modulate both the probability and pattern of evoked AP firing via a fundamentally different mechanism from long-term potentiation and long-term depression.
authors.affiliation: Department of Cell Biology and Anatomy, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
authors.forename: Iaroslav
authors.initials: I
authors.lastname: Savtchouk
authors.forename: Siqiong June
authors.initials: SJ
authors.lastname: Liu
mesh_terms: D000200:Action Potentials; D000818:Animals; D002531:Cerebellum / Q000502:physiology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials; D005239:Fear; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D009412:Nerve Fibers / Q000502:physiology; D009473:Neuronal Plasticity; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000235:genetics / Q000502:physiology*; D013315:Stress, Psychological / Q000503:physiopathology / Q000523:psychology; D013569:Synapses / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; C104722:glutamate receptor ionotropic, AMPA 2