A specific requirement of Arc/Arg3.1 for visual experience-induced homeostatic synaptic plasticity in mouse primary visual cortex.
Visual experience scales down excitatory synapses in the superficial layers of visual cortex in a process that provides an in vivo paradigm of homeostatic synaptic scaling. Experience-induced increases in neural activity rapidly upregulates mRNAs of immediate early genes involved in synaptic plasticity, one of which is Arc (activity-regulated cytoskeleton protein or Arg3.1). Cell biological studies indicate that Arc/Arg3.1 protein functions to recruit endocytic machinery for AMPA receptor internalization, and this action, together with its activity-dependent expression, rationalizes a role for Arc/Arg3.1 in homeostatic synaptic scaling. Here, we investigated the role of Arc/Arg3.1 in homeostatic scaling in vivo by examining experience-dependent development of layer 2/3 neurons in the visual cortex of Arc/Arg3.1 knock-out (KO) mice. Arc/Arg3.1 KOs show minimal changes in basal and developmental regulation of excitatory synaptic strengths but display a profound deficit in homeostatic regulation of excitatory synapses by visual experience. As additional evidence of specificity, we found that the visual experience-induced regulation of inhibitory synapses is normal, although the basal inhibitory synaptic strength is increased in the Arc/Arg3.1 KOs. Our results demonstrate that Arc/Arg3.1 plays a selective role in regulating visual experience-dependent homeostatic plasticity of excitatory synaptic transmission in vivo.
Gao
Ming
M
Department of Biology, College of Chemical and Life Sciences, University of Maryland, College Park, Maryland 20742, USA.
Sossa
Kenneth
K
Song
Lihua
L
Errington
Lauren
L
Cummings
Laurel
L
Hwang
Hongik
H
Kuhl
Dietmar
D
Worley
Paul
P
Lee
Hey-Kyoung
HK
D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D019921:Biotinylation / Q000379:methods; D003598:Cytoskeletal Proteins / Q000172:deficiency / Q000378:metabolism*; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D010775:Photic Stimulation / Q000379:methods*; D017470:Receptors, Glutamate / Q000378:metabolism; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013997:Time Factors; D014793:Visual Cortex / Q000166:cytology / Q000502:physiology*
D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D017470:Receptors, Glutamate; C092069:activity regulated cytoskeletal-associated protein; D010751:Phosphopyruvate Hydratase