A Circadian Clock in the Retina Regulates Rod-Cone Gap Junction Coupling and Neuronal Light Responses via Activation of Adenosine A2A Receptors
Autor: | Christophe P. Ribelayga, Stuart C. Mangel, Jiexin Cao |
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Rok vydání: | 2021 |
Předmět: |
circadian rhythm
0301 basic medicine genetic structures rod-cone coupling Circadian clock Adenosine A2A receptor horizontal cells lcsh:RC321-571 gap junction Melatonin 03 medical and health sciences Cellular and Molecular Neuroscience cones 0302 clinical medicine medicine Circadian rhythm dopamine D4 receptor lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Original Research Retina Adenosine transport Chemistry Gap junction Adenosine Cell biology 030104 developmental biology medicine.anatomical_structure adenosine Cellular Neuroscience A2A receptors sense organs 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Frontiers in Cellular Neuroscience, Vol 14 (2021) Frontiers in Cellular Neuroscience |
ISSN: | 1662-5102 |
DOI: | 10.3389/fncel.2020.605067 |
Popis: | Adenosine, a major neuromodulator in the central nervous system (CNS), is involved in a variety of regulatory functions such as the sleep/wake cycle. Because exogenous adenosine displays dark- and night-mimicking effects in the vertebrate retina, we tested the hypothesis that a circadian (24 h) clock in the retina uses adenosine to control neuronal light responses and information processing. Using a variety of techniques in the intact goldfish retina including measurements of adenosine overflow and content, tracer labeling, and electrical recording of the light responses of cone photoreceptor cells and cone horizontal cells (cHCs), which are post-synaptic to cones, we demonstrate that a circadian clock in the retina itself—but not activation of melatonin or dopamine receptors—controls extracellular and intracellular adenosine levels so that they are highest during the subjective night. Moreover, the results show that the clock increases extracellular adenosine at night by enhancing adenosine content so that inward adenosine transport ceases. Also, we report that circadian clock control of endogenous cone adenosine A2A receptor activation increases rod-cone gap junction coupling and rod input to cones and cHCs at night. These results demonstrate that adenosine and A2A receptor activity are controlled by a circadian clock in the retina, and are used by the clock to modulate rod-cone electrical synapses and the sensitivity of cones and cHCs to very dim light stimuli. Moreover, the adenosine system represents a separate circadian-controlled pathway in the retina that is independent of the melatonin/dopamine pathway but which nevertheless acts in concert to enhance the day/night difference in rod-cone coupling. |
Databáze: | OpenAIRE |
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