Aberrant Activity in Degenerated Retinas Revealed by Electrical Imaging

In this review, I present and discuss the current understanding of aberrant electrical activity found in the ganglion cell layer (GCL) of rod-degenerated (rd) mouse retinas. The reported electrophysiological properties revealed by electrical imaging using high-density microelectrode arrays can be subdivided between spiking activity originating from retinal ganglion cells (RGCs) and local field potentials (LFPs) reflecting strong trans-membrane currents within the GCL. RGCs in rd retinas show increased and rhythmic spiking compared to age-matched wild-type retinas. Fundamental spiking frequencies range from 5 to 15 Hz in various mouse models. The rhythmic RGC spiking is driven by a presynaptic network comprising AII amacrine and bipolar cells. In the healthy retina this rhythm-generating circuit is inhibited by photoreceptor input. A unique physiological feature of rd retinas is rhythmic LFP manifested as spatially-restricted low-frequency (5–15 Hz) voltage changes. Their spatiotemporal characterization revealed propagation and correlation with RGC spiking. LFPs rely on gap-junctional coupling and are shaped by glycinergic and by GABAergic transmission. The aberrant RGC spiking and LFPs provide a simple readout of the functionality of the remaining retinal circuitry which can be used in the development of improved vision restoration strategies.

[1]  R. Masland,et al.  Restoration of visual function in retinal degeneration mice by ectopic expression of melanopsin , 2008, Proceedings of the National Academy of Sciences.

[2]  Luca Berdondini,et al.  Active pixel sensor array for high spatio-temporal resolution electrophysiological recordings from single cell to large scale neuronal networks. , 2009, Lab on a chip.

[3]  Douglas S Kim,et al.  Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration , 2008, Nature Neuroscience.

[4]  Enrica Strettoi,et al.  Retinal organization in the retinal degeneration 10 (rd10) mutant mouse: A morphological and ERG study , 2007, The Journal of comparative neurology.

[5]  G. Awatramani,et al.  Intrinsic oscillatory activity arising within the electrically coupled AII amacrine–ON cone bipolar cell network is driven by voltage‐gated Na+ channels , 2012, The Journal of physiology.

[6]  Thomas Euler,et al.  Multiple Independent Oscillatory Networks in the Degenerating Retina , 2015, Front. Cell. Neurosci..

[7]  D. Schmitt-Landsiedel,et al.  A 128 /spl times/ 128 CMOS bio-sensor array for extracellular recording of neural activity , 2003, 2003 IEEE International Solid-State Circuits Conference, 2003. Digest of Technical Papers. ISSCC..

[8]  F. Müller,et al.  Pharmacological Analysis of Intrinsic Neuronal Oscillations in rd10 Retina , 2014, PloS one.

[9]  Andreas Moller,et al.  A CMOS-based sensor array for in-vitro neural tissue interfacing with 4225 recording sites and 1024 stimulation sites , 2014, 2014 IEEE Biomedical Circuits and Systems Conference (BioCAS) Proceedings.

[10]  Y. Goo,et al.  The slow wave component of retinal activity in rd/rd mice recorded with a multi-electrode array , 2007, Physiological measurement.

[11]  A. Dizhoor,et al.  Ectopic Expression of a Microbial-Type Rhodopsin Restores Visual Responses in Mice with Photoreceptor Degeneration , 2006, Neuron.

[12]  Xiaofeng Ma,et al.  Spontaneous Activity Promotes Synapse Formation in a Cell-Type-Dependent Manner in the Developing Retina , 2012, The Journal of Neuroscience.

[13]  Xin Wang,et al.  Retinal Oscillations Carry Visual Information to Cortex , 2008, Front. Syst. Neurosci..

[14]  A. Maccione,et al.  Large-scale, high-resolution electrophysiological imaging of field potentials in brain slices with microelectronic multielectrode arrays , 2012, Front. Neural Circuits.

[15]  Abduqodir H. Toychiev,et al.  Correlated Spontaneous Activity Persists in Adult Retina and Is Suppressed by Inhibitory Inputs , 2013, PloS one.

[16]  E. Strettoi,et al.  Retinal Ganglion Cells Survive and Maintain Normal Dendritic Morphology in a Mouse Model of Inherited Photoreceptor Degeneration , 2008, The Journal of Neuroscience.

[17]  B. Eversmann,et al.  A 128 × 128 CMOS bio-sensor array for extracellular recording of neural activity , 2003 .

[18]  Thomas Euler,et al.  Bulk electroporation and population calcium imaging in the adult mammalian retina. , 2011, Journal of neurophysiology.

[19]  U. Frey,et al.  Single-chip microelectronic system to interface with living cells. , 2007, Biosensors & bioelectronics.

[20]  M. Tachibana,et al.  Synchronized retinal oscillations encode essential information for escape behavior in frogs , 2005, Nature Neuroscience.

[21]  C. Koch,et al.  The origin of extracellular fields and currents — EEG, ECoG, LFP and spikes , 2012, Nature Reviews Neuroscience.

[22]  Brian Litt,et al.  Flexible, Foldable, Actively Multiplexed, High-Density Electrode Array for Mapping Brain Activity in vivo , 2011, Nature Neuroscience.

[23]  Siegrid Löwel,et al.  Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell-Tailored Optogenetic Tool , 2015, PLoS biology.

[24]  J. Menzler,et al.  Rhythmic Ganglion Cell Activity in Bleached and Blind Adult Mouse Retinas , 2014, PloS one.

[25]  Vittorio Porciatti,et al.  Morphological and Functional Abnormalities in the Inner Retina of the rd/rd Mouse , 2002, The Journal of Neuroscience.

[26]  C. Kim,et al.  Temporal response properties of retinal ganglion cells in rd1 mice evoked by amplitude-modulated electrical pulse trains. , 2010, Investigative ophthalmology & visual science.

[27]  Stefano Panzeri,et al.  Modelling and analysis of local field potentials for studying the function of cortical circuits , 2013, Nature Reviews Neuroscience.

[28]  Patrick Degenaar,et al.  This Work Is Licensed under a Creative Commons Attribution 4.0 International License Blockade of Pathological Retinal Ganglion Cell Hyperactivity Improves Optogenetically Evoked Light Responses in Rd1 Mice , 2022 .

[29]  R. Baldoni,et al.  Aberrant activity in retinal degeneration impairs central visual processing and relies on Cx36-containing gap junctions. , 2016, Experimental eye research.

[30]  N. Cuenca,et al.  Functional and structural modifications during retinal degeneration in the rd10 mouse , 2008, Neuroscience.

[31]  Béla Völgyi,et al.  Light increases the gap junctional coupling of retinal ganglion cells , 2010, The Journal of physiology.

[32]  Armin Lambacher,et al.  Axonal Transmission in the Retina Introduces a Small Dispersion of Relative Timing in the Ganglion Cell Population Response , 2011, PloS one.

[33]  B. Sagdullaev,et al.  Aberrant synaptic input to retinal ganglion cells varies with morphology in a mouse model of retinal degeneration , 2014, The Journal of comparative neurology.

[34]  P. Greenberg,et al.  Retinal implants: a systematic review , 2014, British Journal of Ophthalmology.

[35]  B. Sagdullaev,et al.  Network Deficiency Exacerbates Impairment in a Mouse Model of Retinal Degeneration , 2012, Front. Syst. Neurosci..

[36]  S. Stasheff,et al.  Emergence of sustained spontaneous hyperactivity and temporary preservation of OFF responses in ganglion cells of the retinal degeneration (rd1) mouse. , 2008, Journal of neurophysiology.

[37]  E J Chichilnisky,et al.  A Polyaxonal Amacrine Cell Population in the Primate Retina , 2014, The Journal of Neuroscience.

[38]  Michael P. Andrews,et al.  Developmental time course distinguishes changes in spontaneous and light-evoked retinal ganglion cell activity in rd1 and rd10 mice. , 2011, Journal of neurophysiology.

[39]  Luca Berdondini,et al.  Following the ontogeny of retinal waves: pan-retinal recordings of population dynamics in the neonatal mouse , 2013, The Journal of physiology.

[40]  P. Detwiler,et al.  Network Oscillations Drive Correlated Spiking of ON and OFF Ganglion Cells in the rd1 Mouse Model of Retinal Degeneration , 2014, PloS one.

[41]  Gautam B Awatramani,et al.  An Intrinsic Neural Oscillator in the Degenerating Mouse Retina , 2011, The Journal of Neuroscience.

[42]  D. Baylor,et al.  Synchronous bursts of action potentials in ganglion cells of the developing mammalian retina. , 1991, Science.

[43]  P. Fromherz.  Electrical interfacing of nerve cells and semiconductor chips. , 2002, Chemphyschem : a European journal of chemical physics and physical chemistry.

[44]  S. Han,et al.  Spontaneous Oscillatory Rhythm in Retinal Activities of Two Retinal Degeneration (rd1 and rd10) Mice , 2011, The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology.

[45]  Günther Zeck,et al.  Network Oscillations in Rod-Degenerated Mouse Retinas , 2011, The Journal of Neuroscience.

[46]  L. Peichl.  Retinal ganglion cells , 1988 .

[47]  Rachel O.L. Wong,et al.  Failure to Maintain Eye-Specific Segregation in nob, a Mutant with Abnormally Patterned Retinal Activity , 2006, Neuron.

[48]  Elena Ivanova,et al.  Block of Gap Junctions Eliminates Aberrant Activity and Restores Light Responses during Retinal Degeneration , 2013, The Journal of Neuroscience.

[49]  R. Wong,et al.  Developmental Loss of Synchronous Spontaneous Activity in the Mouse Retina Is Independent of Visual Experience , 2003, The Journal of Neuroscience.

[50]  Alfred Stett,et al.  Subretinal electronic chips allow blind patients to read letters and combine them to words , 2010, Proceedings of the Royal Society B: Biological Sciences.

[51]  Gaute T. Einevoll,et al.  Modelling and Analysis of Electrical Potentials Recorded in Microelectrode Arrays (MEAs) , 2015, Neuroinformatics.

[52]  Daniel Palanker,et al.  Contrast Sensitivity With a Subretinal Prosthesis and Implications for Efficient Delivery of Visual Information. , 2015, Investigative ophthalmology & visual science.

[53]  Mark S. Cembrowski,et al.  Intrinsic bursting of AII amacrine cells underlies oscillations in the rd1 mouse retina. , 2014, Journal of neurophysiology.

[54]  G. Awatramani,et al.  Origins of spontaneous activity in the degenerating retina , 2015, Front. Cell. Neurosci..

[55]  Srinivas R. Sadda,et al.  Electrical stimulation in normal and retinal degeneration (rd1) isolated mouse retina , 2006, Vision Research.

[56]  Thomas Euler,et al.  Functional Stability of Retinal Ganglion Cells after Degeneration-Induced Changes in Synaptic Input , 2008, The Journal of Neuroscience.

[57]  Iman H. Brivanlou,et al.  Mechanisms of Concerted Firing among Retinal Ganglion Cells , 1998, Neuron.

[58]  Ulrich Egert,et al.  Biological application of microelectrode arrays in drug discovery and basic research , 2003, Analytical and bioanalytical chemistry.

[59]  Karl Deisseroth,et al.  Genetic Reactivation of Cone Photoreceptors Restores Visual Responses in Retinitis Pigmentosa , 2010, Science.

[60]  B. Lin,et al.  Retinal Ganglion Cells are Resistant to Photoreceptor Loss in Retinal Degeneration , 2013, PloS one.

[61]  A. Sher,et al.  Photovoltaic restoration of sight with high visual acuity , 2015, Nature Medicine.