title: Network oscillations in rod-degenerated mouse retinas.
abstract: In the mammalian retina, excitatory and inhibitory circuitries enable retinal ganglion cells (RGCs) to signal the occurrence of visual features to higher brain areas. This functionality disappears in certain diseases of retinal degeneration because of the progressive loss of photoreceptors. Recent work in a mouse model of retinal degeneration (rd1) found that, although some intraretinal circuitry is preserved and RGCs maintain characteristic physiological properties, they exhibit increased and aberrant rhythmic activity. Here, extracellular recordings were made to assess the degree of aberrant activity in adult rd1 retinas and to investigate the mechanism underlying such behavior. A multi-transistor array with thousands of densely packed sensors allowed for simultaneous recordings of spiking activity in populations of RGCs and of local field potentials (LFPs). The majority of identified RGCs displayed rhythmic (7-10 Hz) but asynchronous activity. The spiking activity correlated with the LFPs, which reflect an average synchronized excitatory input to the RGCs. LFPs initiated from random positions and propagated across the retina. They disappeared when ionotrophic glutamate receptors or electrical synapses were blocked. They persisted in the presence of other pharmacological blockers, including TTX and inhibitory receptor antagonists. Our results suggest that excitation-transmitted laterally through a network of electrically coupled interneurons-leads to large-scale retinal network oscillations, reflected in the rhythmic spiking of most rd1 RGCs. This result may explain forms of photopsias reported by blind patients, while the mechanism involved should be considered in future treatment strategies targeting the disease of retinitis pigmentosa.
authors.affiliation: Department of Systems and Computational Neuroscience, Max Planck Institute of Neurobiology, D-82152 Martinsried, Germany.
authors.forename: Jacob
authors.initials: J
authors.lastname: Menzler
authors.forename: Günther
authors.initials: G
authors.lastname: Zeck
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000367:Age Factors; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004195:Disease Models, Animal; D005074:Evoked Potentials, Visual / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D017629:Gap Junctions / Q000187:drug effects / Q000235:genetics; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D066298:In Vitro Techniques; D008027:Light; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology*; D009433:Neural Inhibition / Q000187:drug effects; D010507:Periodicity; D011724:Pyridazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012162:Retinal Degeneration / Q000235:genetics / Q000473:pathology*; D017948:Retinal Rod Photoreceptor Cells / Q000187:drug effects / Q000502:physiology*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013223:Statistics as Topic; D013779:Tetrodotoxin / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D011724:Pyridazines; D011810:Quinoxalines; D026941:Sodium Channel Blockers; D018698:Glutamic Acid; D013779:Tetrodotoxin; D008469:Meclofenamic Acid; D005680:gamma-Aminobutyric Acid; C056723:FG 9041; D015763:2-Amino-5-phosphonovalerate; C049853:gabazine; D002229:Carbenoxolone; C031231:2-amino-7-phosphonoheptanoic acid; D005998:Glycine