title: Visual circuit development requires patterned activity mediated by retinal acetylcholine receptors.
abstract: The elaboration of nascent synaptic connections into highly ordered neural circuits is an integral feature of the developing vertebrate nervous system. In sensory systems, patterned spontaneous activity before the onset of sensation is thought to influence this process, but this conclusion remains controversial, largely due to the inherent difficulty recording neural activity in early development. Here, we describe genetic and pharmacological manipulations of spontaneous retinal activity, assayed in vivo, that demonstrate a causal link between retinal waves and visual circuit refinement. We also report a decoupling of downstream activity in retinorecipient regions of the developing brain after retinal wave disruption. Significantly, we show that the spatiotemporal characteristics of retinal waves affect the development of specific visual circuits. These results conclusively establish retinal waves as necessary and instructive for circuit refinement in the developing nervous system and reveal how neural circuits adjust to altered patterns of activity prior to experience.
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Burbridge
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Hong-Ping
authors.initials: HP
authors.lastname: Xu
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: James B
authors.initials: JB
authors.lastname: Ackman
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Ge
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Yueyi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Mei-Jun
authors.initials: MJ
authors.lastname: Ye
authors.affiliation: Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Z Jimmy
authors.initials: ZJ
authors.lastname: Zhou
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
authors.forename: Anis
authors.initials: A
authors.lastname: Contractor
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA; Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06510, USA; Kavli Institute for Neuroscience, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: michael.crair@yale.edu.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Crair
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D007839:Functional Laterality; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D066298:In Vitro Techniques; D008469:Meclofenamic Acid / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology; D014795:Visual Pathways / Q000254:growth & development*
chemical_list: D002118:Calcium; D000242:Cyclic AMP; D006152:Cyclic GMP; D016861:Cyclooxygenase Inhibitors; D005136:Eye Proteins; D018398:Homeodomain Proteins; D008469:Meclofenamic Acid; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; D012097:Repressor Proteins; C000605732:Pax6 protein, mouse