Retinocollicular synapse maturation and plasticity are regulated by correlated retinal waves.
During development, spontaneous retinal waves are thought to provide an instructive signal for retinotopic map formation in the superior colliculus. In mice lacking the beta2 subunit of nicotinic ACh receptors (beta2-/-), correlated retinal waves are absent during the first postnatal week, but return during the second postnatal week. In control retinocollicular synapses, in vitro analysis reveals that AMPA/NMDA ratios and AMPA quantal amplitudes increase during the first postnatal week while the prevalence of silent synapses decreases. In age-matched beta2-/- mice, however, these parameters remain unchanged through the first postnatal week in the absence of retinal waves, but quickly mature to control levels by the end of the second week, suggesting that the delayed onset of correlated waves is able to drive synapse maturation. To examine whether such a mechanistic relationship exists, we applied a "burst-based" plasticity protocol that mimics coincident activity during retinal waves. We find that this pattern of activation is indeed capable of inducing synaptic strengthening [long-term potentiation (LTP)] on average across genotypes early in the first postnatal week [postnatal day 3 (P3) to P4] and, interestingly, that the capacity for LTP at the end of the first week (P6-P7) is significantly greater in immature beta2-/- synapses than in mature control synapses. Together, our results suggest that retinal waves drive retinocollicular synapse maturation through a learning rule that is physiologically relevant to natural wave statistics and that these synaptic changes may serve an instructive role during retinotopic map refinement.
Shah
Ruchir D
RD
Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Crair
Michael C
MC
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D016202:N-Methylaspartate / Q000378:metabolism; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D011810:Quinoxalines / Q000494:pharmacology; D011978:Receptors, Nicotinic / Q000172:deficiency; D012160:Retina / Q000502:physiology*; D013477:Superior Colliculi / Q000502:physiology*; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D014795:Visual Pathways / Q000502:physiology; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D016202:N-Methylaspartate; D011810:Quinoxalines; D011978:Receptors, Nicotinic; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline