title: Light adaptation increases response latency of alpha ganglion cells via a threshold-like nonlinearity.
abstract: Adaptation is an important process of sensory systems to adjust sensitivity to ensure the appropriate information encoding. Sensitivity and kinetics of retinal ganglion cell (RGC) responses have been studied extensively using a brief flash superimposed on different but steady backgrounds. However, it is still unclear if light adaptation exerts any effect on more complex response properties, such as response nonlinearity. In this study, we found that the latency of spike responses to a repeated flashing spot stimulation increased by 30 ms in the mouse ON α RGCs (An ON-type RGC is excited when a spot is turned on in the center of its receptive field). A single dimming event preceding the test flash on a steady adapting background could also produce similar effect in increasing latency of light responses. A simple computational model with a linear transformation of the light stimulus and a threshold-like nonlinearity could account for the experimental data. Moreover, the strength of the measured nonlinearity and the response latency were affected by the duration of light adaptation. The possible biological processes underlying this nonlinearity were explored. Voltage clamp recording revealed the presence of the increase in latency and threshold-like nonlinearity in the excitatory input of RGCs. However, no comparable nonlinearity was observed in the light responses of the ON cone bipolar cells. We further excluded GABAergic and glycinergic inhibition, N-methyl-D-aspartate receptor rectification and voltage-gated Na(+) channels as potential sources of this nonlinearity by pharmacological experiments. Our results indicate the bipolar cell terminals as the potential site of nonlinearity. Computational modeling constrained by experimental data supports that conclusion and suggests the voltage-sensitive Ca(++) channels and Ca(++)-dependent vesicle release in the bipolar cell terminals as mechanistic basis.
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China; University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China. Electronic address: stevenlechang@gmail.com.
authors.forename: L
authors.initials: L
authors.lastname: Chang
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China; School of Biomedical Engineering, Bio-X Research Center and Institute of Natural Sciences, Shanghai Jiao Tong University, 800 Dong-Chuan Road, Shanghai 200240, China. Electronic address: shiganghe@sjtu.edu.cn.
authors.forename: S
authors.initials: S
authors.lastname: He
mesh_terms: D000221:Adaptation, Ocular / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D055592:Biophysical Phenomena; D003198:Computer Simulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008959:Models, Neurological; D017711:Nonlinear Dynamics; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D011930:Reaction Time / Q000502:physiology*; D012160:Retina / Q000166:cytology*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018691:Excitatory Amino Acid Antagonists; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine
keywords: 2-amino-5-phosphonopentanoic acid; 4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid; AP-5; AS; EGTA; HEPES; I–R function; LN model; N-methyl-d-aspartate; NMDA; RGC; adapting stimulus; alpha retinal ganglion cell; ethylene glycol tetraacetic acid; intensity–response function; light adaptation; linear–nonlinear cascade model; mGluR6; metabotropic glutamate receptors; mouse; nonlinearity; response latency; retinal ganglion cell