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Cannabinoids modulate spontaneous synaptic activity in retinal ganglion cells

Published online by Cambridge University Press:  12 July 2011

T. P. MIDDLETON  and
D. A. PROTTI
T. P. MIDDLETON
Affiliation:
Discipline of Physiology, The University of Sydney, Sydney, New South Wales, Australia Bosch Institute, The University of Sydney, Sydney, New South Wales, Australia
D. A. PROTTI*
Affiliation:
Discipline of Physiology, The University of Sydney, Sydney, New South Wales, Australia Bosch Institute, The University of Sydney, Sydney, New South Wales, Australia
*
*Address correspondence and reprint requests to: Dario Protti, Room N659, Anderson Stuart Building F13, The University of Sydney, Sydney, NSW 2006, Australia. E-mail: [email protected]
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Abstract

The endocannabinoid (ECB) system has been found throughout the central nervous system and modulates cell excitability in various forms of short-term plasticity. ECBs and their receptors have also been localized to all retinal cells, and cannabinoid receptor activation has been shown to alter voltage-dependent conductances in several different retinal cell types, suggesting a possible role for cannabinoids in retinal processing. Their effects on synaptic transmission in the mammalian retina, however, have not been previously investigated. Here, we show that exogenous cannabinoids alter spontaneous synaptic transmission onto retinal ganglion cells (RGCs). Using whole-cell voltage-clamp recordings in whole-mount retinas, we measured spontaneous postsynaptic currents (SPSCs) in RGCs in adult and young (P14–P21) mice. We found that the addition of an exogenous cannabinoid agonist, WIN55212-2 (5 μM), caused a significant reversible reduction in the frequency of SPSCs. This change, however, did not alter the kinetics of the SPSCs, indicating a presynaptic locus of action. Using blockers to isolate inhibitory or excitatory currents, we found that cannabinoids significantly reduced the release probability of both GABA and glutamate, respectively. While the addition of cannabinoids reduced the frequency of both GABAergic and glutamatergic SPSCs in both young and adult mice, we found that the largest effect was on GABA-mediated currents in young mice. These results suggest that the ECB system may potentially be involved in the modulation of signal transmission in the retina. Furthermore, they suggest that it might play a role in the developmental maturation of synaptic circuits, and that exogenous cannabinoids are likely able to disrupt retinal processing and consequently alter vision.

Keywords

WIN55212-2RetinaSpontaneous synaptic currentsPatch clampWhole-mount retina
Type
Research Articles
Information
Visual Neuroscience , Volume 28 , Issue 5 , September 2011 , pp. 393 - 402
Copyright
Copyright © Cambridge University Press 2011

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