Synaptic inputs to retinal ganglion cells that set the circadian clock

Jorge Alberto Perez-Leon; Erin J Warren; Charles N Allen; David W Robinson; R Lane Brown

doi:10.1111/j.1460-9568.2006.04999.x

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Synaptic inputs to retinal ganglion cells that set the circadian clock

Journal article

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Peer reviewed

Synaptic inputs to retinal ganglion cells that set the circadian clock

Jorge Alberto Perez-Leon, Erin J Warren, Charles N Allen, David W Robinson and R Lane Brown

The European journal of neuroscience, Vol.24(4), pp.1117-1123

08/2006

DOI: https://doi.org/10.1111/j.1460-9568.2006.04999.x

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https://hdl.handle.net/2376/112605

PMCID: PMC2435212

PMID: 16930437

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Abstract

Excitatory Amino Acid Antagonists - metabolism

GABA Antagonists - metabolism

Receptors, Glutamate - metabolism

Synaptic Transmission - physiology

Rats

Circadian Rhythm - physiology

Quinoxalines - metabolism

Glycine Agents - metabolism

Kynurenic Acid - metabolism

Retinal Ganglion Cells - metabolism

Neural Pathways - physiology

Rats, Sprague-Dawley

Bicuculline - metabolism

Retinal Ganglion Cells - cytology

Patch-Clamp Techniques

Animals

Strychnine - metabolism

Synapses - metabolism

Biological Clocks - physiology

Light

Rod Opsins - metabolism

Receptors, GABA - metabolism

Neural Pathways - metabolism

Tetrodotoxin - metabolism

Melanopsin-containing retinal ganglion cells (RGCs) project to the suprachiasmatic nuclei (SCN) and mediate photoentrainment of the circadian system. Melanopsin is a novel retinal-based photopigment that renders these cells intrinsically photosensitive (ip). Although genetic ablation of melanopsin abolishes the intrinsic light response, it has a surprisingly minor effect on circadian photoentrainment. This and other non-visual responses to light are lost only when the melanopsin deficiency is coupled with mutations that disable classical rod and cone photoreceptors, suggesting that melanopsin-containing RGCs also receive rod- and cone-driven synaptic inputs. Using whole-cell patch-clamp recording, we demonstrate that light triggers synaptic currents in ipRGCs via activation of ionotropic glutamate and gamma-aminobutyric acid (GABA) receptors. Miniature postsynaptic currents (mPSCs) were clearly observed in ipRGCs, although they were less robust and were seen less frequently than those seen in non-ip cells. Pharmacological treatments revealed that the majority of ipRGCs receive excitatory glutamatergic inputs that were blocked by DNQX and/or kynurenic acid, as well as inhibitory GABAergic inputs that were blocked by bicuculline. Other ipRGCs received either glutamatergic or GABAergic inputs nearly exclusively. Although strychnine (Strych)-sensitive mPSCs were evident on many non-ipRGCs, indicating the presence of glycinergic inputs, we saw no evidence of Strych-sensitive events in ipRGCs. Based on these results, it is clear that SCN-projecting RGCs can respond to light both via an intrinsic melanopsin-based signaling cascade and via a synaptic pathway driven by classical rod and/or cone photoreceptors. It remains to be determined how the ipRGCs integrate these temporally distinct inputs to generate the signals that mediate circadian photoentrainment and other non-visual responses to light.

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Title: Synaptic inputs to retinal ganglion cells that set the circadian clock
Creators: Jorge Alberto Perez-Leon - Neurological Sciences Institute, Oregon Health and Science University, Beaverton, OR 97006, USA
Erin J Warren
Charles N Allen
David W Robinson
R Lane Brown
Publication Details: The European journal of neuroscience, Vol.24(4), pp.1117-1123
Academic Unit: Integrative Physiology and Neuroscience, Department of
Publisher: France
Grant note: MH-67094 / NIMH NIH HHS R01 MH067094 / NIMH NIH HHS R01 MH067094-03 / NIMH NIH HHS
Identifiers: 99900547404501842
Language: English
Resource Type: Journal article