Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells

Loïs S. Miraucourt, Jennifer Tsui, Delphine Gobert, Jean François Desjardins, Anne Schohl, Mari Sild, Perry Spratt, Annie Castonguay, Yves De Koninck, Nicholas Marsh-Armstrong, Paul W. Wiseman, Edward S. Ruthazer

Research output: Contribution to journalArticle

Abstract

Type 1 cannabinoid receptors (CB1Rs) are widely expressed in the vertebrate retina, but the role of endocannabinoids in vision is not fully understood. Here, we identified a novel mechanism underlying a CB1R-mediated increase in retinal ganglion cell (RGC) intrinsic excitability acting through AMPK-dependent inhibition of NKCC1 activity. Clomeleon imaging and patch clamp recordings revealed that inhibition of NKCC1 downstream of CB1R activation reduces intracellular Cl- levels in RGCs, hyperpolarizing the resting membrane potential. We confirmed that such hyperpolarization enhances RGC action potential firing in response to subsequent depolarization, consistent with the increased intrinsic excitability of RGCs observed with CB1R activation. Using a dot avoidance assay in freely swimming Xenopus tadpoles, we demonstrate that CB1R activation markedly improves visual contrast sensitivity under low-light conditions. These results highlight a role for endocannabinoids in vision and present a novel mechanism for cannabinoid modulation of neuronal activity through Cl- regulation.

Original languageEnglish (US)
Article numbere15932
JournaleLife
Volume5
Issue numberAUGUST
DOIs
StatePublished - Aug 8 2016

Fingerprint

Endocannabinoids
Retinal Ganglion Cells
Chlorides
Inhibition (Psychology)
Cape Verde
Modulation
Cannabinoid Receptors
Contrast Sensitivity
AMP-Activated Protein Kinases
Cannabinoids
Xenopus
Membrane Potentials
Action Potentials
Larva
Vertebrates
Retina
Adenofibroma
Bronchiolo-Alveolar Adenocarcinoma
Beryllium
Depolarization

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Medicine(all)
  • Neuroscience(all)

Cite this

Miraucourt, L. S., Tsui, J., Gobert, D., Desjardins, J. F., Schohl, A., Sild, M., ... Ruthazer, E. S. (2016). Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells. eLife, 5(AUGUST), [e15932]. DOI: 10.7554/eLife.15932.001

Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells. / Miraucourt, Loïs S.; Tsui, Jennifer; Gobert, Delphine; Desjardins, Jean François; Schohl, Anne; Sild, Mari; Spratt, Perry; Castonguay, Annie; De Koninck, Yves; Marsh-Armstrong, Nicholas; Wiseman, Paul W.; Ruthazer, Edward S.

In: eLife, Vol. 5, No. AUGUST, e15932, 08.08.2016.

Research output: Contribution to journalArticle

Miraucourt, LS, Tsui, J, Gobert, D, Desjardins, JF, Schohl, A, Sild, M, Spratt, P, Castonguay, A, De Koninck, Y, Marsh-Armstrong, N, Wiseman, PW & Ruthazer, ES 2016, 'Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells' eLife, vol 5, no. AUGUST, e15932. DOI: 10.7554/eLife.15932.001
Miraucourt LS, Tsui J, Gobert D, Desjardins JF, Schohl A, Sild M et al. Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells. eLife. 2016 Aug 8;5(AUGUST). e15932. Available from, DOI: 10.7554/eLife.15932.001

Miraucourt, Loïs S.; Tsui, Jennifer; Gobert, Delphine; Desjardins, Jean François; Schohl, Anne; Sild, Mari; Spratt, Perry; Castonguay, Annie; De Koninck, Yves; Marsh-Armstrong, Nicholas; Wiseman, Paul W.; Ruthazer, Edward S. / Endocannabinoid signaling enhances visual responses through modulation of intracellular chloride levels in retinal ganglion cells.

In: eLife, Vol. 5, No. AUGUST, e15932, 08.08.2016.

Research output: Contribution to journalArticle

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