title: Mechanisms underlying developmental changes in the firing patterns of ON and OFF retinal ganglion cells during refinement of their central projections.
abstract: Patterned neuronal activity is implicated in the refinement of connectivity during development. Calcium-imaging studies of the immature ferret visual system demonstrated previously that functionally separate ON and OFF retinal ganglion cells (RGCs) develop distinct temporal patterns of spontaneous activity as their axonal projections undergo refinement. OFF RGCs become spontaneously more active compared with ON cells, resulting in a decrease in synchronous activity between these cell types. This change in ON and OFF activity patterns is suitable for driving the activity-dependent refinement of their axonal projections. Here, we used whole-cell and perforated-patch recording techniques to elucidate the mechanisms that underlie the developmental alteration in the ON and OFF RGC activity patterns. First, we show that before the refinement period, ON and OFF RGCs have similar spike patterns; however, during the period of segregation, OFF RGCs demonstrate significantly higher spike rates relative to ON cells. With increasing age, OFF cells require less depolarization to reach their action potential threshold and fire more spikes in response to current injection compared with ON cells. In addition, spontaneous postsynaptic currents and potentials are greater in magnitude in OFF cells than ON cells. In contrast, before axonal refinement, there are no differences in the intrinsic excitability or synaptic drive onto ON and OFF cells. Together, our results show that developmental changes in ON and OFF RGC excitability and in the strength of their synaptic drives act together to reshape the spike patterns of these cells in a manner appropriate for the refinement of their connectivity.
authors.affiliation: Department of Anatomy, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: K L
authors.initials: KL
authors.lastname: Myhr
authors.forename: P D
authors.initials: PD
authors.lastname: Lukasiewicz
authors.forename: R O
authors.initials: RO
authors.lastname: Wong
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000375:Aging / Q000502:physiology; D000818:Animals; D004079:Dihydro-beta-Erythroidine / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005289:Ferrets; D018756:GABA Antagonists / Q000494:pharmacology; D018684:Glycine Agents / Q000494:pharmacology; D066298:In Vitro Techniques; D018408:Patch-Clamp Techniques; D012160:Retina / Q000166:cytology / Q000254:growth & development* / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000145:classification / Q000187:drug effects / Q000502:physiology; D012684:Sensory Thresholds / Q000187:drug effects / Q000502:physiology; D012815:Signal Processing, Computer-Assisted
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D018684:Glycine Agents; D004079:Dihydro-beta-Erythroidine