title: Segregation of ON and OFF retinogeniculate connectivity directed by patterned spontaneous activity.
abstract: In many parts of the developing nervous system, the early patterns of connectivity are refined by processes that require neuronal activity. These processes are thought to involve Hebbian mechanisms that lead to strengthening and maintenance of inputs that display correlated pre- and postsynaptic activity and elimination of inputs that fire asynchronously. Here we investigated the role of patterned spontaneous retinal activity and Hebbian synaptic mechanisms on segregation of ON and OFF retinal afferents in the dorsal lateral geniculate nucleus (dLGN) of the developing ferret visual system. We recorded extracellularly the spontaneous spike activity of neighboring pairs of ganglion cells and found that OFF cells have significantly higher mean firing rates than ON cells. Spiking is best correlated between cells of the same sign (ON, ON; OFF, OFF) compared with cells of opposite sign (ON, OFF). We then constructed a simple Hebbian model of retinogeniculate synaptic development based on a correlational framework. Using our recorded activity patterns, together with previous calcium-imaging data, we show that endogenous retinal activity, coupled with Hebbian mechanisms of synaptic development, can drive the segregation of ON and OFF retinal inputs to the dLGN. Segregation occurs robustly when heterosynaptic competition is present within time windows of 50-500 ms. In addition, our results suggest that the initial patterns of connectivity (biases in convergence of inputs) and the strength of inhibition in the network each play a crucial role in determining whether ON or OFF inputs dominate at maturity.
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Christopher W
authors.initials: CW
authors.lastname: Lee
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Eglen
authors.forename: Rachel O L
authors.initials: RO
authors.lastname: Wong
mesh_terms: D000465:Algorithms; D000818:Animals; D002118:Calcium / Q000502:physiology; D003198:Computer Simulation; D003463:Cues; D004594:Electrophysiology; D005110:Extracellular Space / Q000502:physiology; D005289:Ferrets / Q000502:physiology*; D005829:Geniculate Bodies / Q000166:cytology / Q000502:physiology*; D016014:Linear Models; D008959:Models, Neurological; D009415:Nerve Net / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology; D012160:Retina / Q000166:cytology / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000502:physiology; D013569:Synapses / Q000502:physiology
chemical_list: D002118:Calcium