Retinal gap junctions are involved in rhythmogenesis of neuronal activity at remote locations - Study on infra-slow oscillations in the rat olivary pretectal nucleus.
A subpopulation of olivary pretectal nucleus (OPN) neurons fire action potentials in a rhythmic manner with an eruption of activity occurring approximately every two minutes. These infra-slow oscillations depend critically on functional retinal input and are subject to modulation by light. Interestingly, the activity of photoreceptors is necessary for the emergence of the rhythm and while classic photoreceptors (rods and cones) are necessary in darkness and dim light, melanopsin photoreceptors are indispensable in bright light. Using pharmacological and electrophysiological approaches in vivo, we show that also blocking retinal gap junctions (GJs), which are expressed by multitude of retinal cells, leads to the disruption of oscillatory activity in the rat OPN. Intravitreal injection of carbenoxolone (CBX) quenched oscillations in a concentration-dependent manner with 1mM being ineffective, 5mM showing partial and 20mM showing complete effectiveness in disrupting oscillations. Moreover, the most effective CBX concentration depressed cone-mediated light-induced responses of oscillatory neurons suggesting that CBX is also acting on targets other than GJs. In contrast, intravitreal injection of meclofenamic acid (MFA, 20mM) led to disruption of the rhythm but did not interfere with cone-mediated light-induced responses of oscillatory neurons, implying that MFA is more specific toward GJs than CBX, as suggested before. We conclude that electrical coupling between various types of retinal cells and resultant synchronous firing of retinal ganglion cells is necessary for the generation of infra-slow oscillations in the rat OPN.
Department of Neurophysiology and Chronobiology, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland.
Patrycja
P
Orlowska-Feuer
Department of Neurophysiology and Chronobiology, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland.
Jagoda S
JS
Jeczmien-Lazur
Department of Anatomy and Cell Biology, 468 Medical Science Building, The Schulich School of Medicine, University of Western Ontario, London, Ontario N6A 5C1, Canada. Electronic address: szkudlarek.edu@gmail.com.
Hanna J
HJ
Szkudlarek
Department of Neurophysiology and Chronobiology, Institute of Zoology, Jagiellonian University, Gronostajowa 9, 30-387 Krakow, Poland. Electronic address: marian.lewandowski@uj.edu.pl.
Marian H
MH
Lewandowski
D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology*; D058449:Intravitreal Injections; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D010507:Periodicity; D018373:Peripheral Nervous System Agents / Q000494:pharmacology; D066250:Pretectal Region / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects / Q000502:physiology*; D014785:Vision, Ocular / Q000187:drug effects / Q000502:physiology
D018373:Peripheral Nervous System Agents; D008469:Meclofenamic Acid; D002229:Carbenoxolone
gap junctions; in vivo electrophysiology; infra-slow rhythm; intraocular injections; light responses