A single fear-inducing stimulus induces a transcription-dependent switch in synaptic AMPAR phenotype.
Changes in emotional state are known to alter neuronal excitability and can modify learning and memory formation. Such experience-dependent neuronal plasticity can be long-lasting and is thought to involve the regulation of gene transcription. We found that a single fear-inducing stimulus increased GluR2 (also known as Gria2) mRNA abundance and promoted synaptic incorporation of GluR2-containing AMPA receptors (AMPARs) in mouse cerebellar stellate cells. The switch in synaptic AMPAR phenotype was mediated by noradrenaline and action potential prolongation. The subsequent rise in intracellular Ca(2+) and activation of Ca(2+)-sensitive ERK/MAPK signaling triggered new GluR2 gene transcription and a switch in the synaptic AMPAR phenotype from GluR2-lacking, Ca(2+)-permeable receptors to GluR2-containing, Ca(2+)-impermeable receptors on the order of hours. The change in glutamate receptor phenotype altered synaptic efficacy in cerebellar stellate cells. Thus, a single fear-inducing stimulus can induce a long-term change in synaptic receptor phenotype and may alter the activity of an inhibitory neural network.
Liu
Yu
Y
Department of Biology, Pennsylvania State University, University Park, Pennsylvania, USA.
Formisano
Luigi
L
Savtchouk
Iaroslav
I
Takayasu
Yukihiro
Y
Szabó
Gábor
G
Zukin
R Suzanne
RS
Liu
Siqiong June
SJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002531:Cerebellum / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005239:Fear / Q000502:physiology*; D005786:Gene Expression Regulation; D020935:MAP Kinase Signaling System / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009638:Norepinephrine / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics* / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D013315:Stress, Psychological / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D014158:Transcription, Genetic
D002118:Calcium; D020746:Calcium Channels, L-Type; D048049:Extracellular Signal-Regulated MAP Kinases; D009638:Norepinephrine; D012333:RNA, Messenger; D018091:Receptors, AMPA; D011943:Receptors, Adrenergic, beta; C104722:glutamate receptor ionotropic, AMPA 2