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Brain Struct Funct. 2016 Jan;221(1):301-16. doi: 10.1007/s00429-014-0908-4. Epub 2014 Oct 2.

Cannabinoid CB1 receptor signaling dichotomously modulates inhibitory and excitatory synaptic transmission in rat inner retina.

Author information

1
Institutes of Brain Science, Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China.
2
Institutes of Brain Science, Institute of Neurobiology, State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Rd, Shanghai, 200032, China. zfwang@fudan.edu.cn.

Abstract

In the inner retina, ganglion cells (RGCs) integrate and process excitatory signal from bipolar cells (BCs) and inhibitory signal from amacrine cells (ACs). Using multiple labeling immunohistochemistry, we first revealed the expression of the cannabinoid CB1 receptor (CB1R) at the terminals of ACs and BCs in rat retina. By patch-clamp techniques, we then showed how the activation of this receptor dichotomously regulated miniature inhibitory postsynaptic currents (mIPSCs), mediated by GABAA receptors and glycine receptors, and miniature excitatory postsynaptic currents (mEPSCs), mediated by AMPA receptors, of RGCs in rat retinal slices. WIN55212-2 (WIN), a CB1R agonist, reduced the mIPSC frequency due to an inhibition of L-type Ca(2+) channels no matter whether AMPA receptors were blocked. In contrast, WIN reduced the mEPSC frequency by suppressing T-type Ca(2+) channels only when inhibitory inputs to RGCs were present, which could be in part due to less T-type Ca(2+) channels of cone BCs, presynaptic to RGCs, being in an inactivation state under such condition. This unique feature of CB1R-mediated retrograde regulation provides a novel mechanism for modulating excitatory synaptic transmission in the inner retina. Moreover, depolarization of RGCs suppressed mIPSCs of these cells, an effect that was eliminated by the CB1R antagonist SR141716, suggesting that endocannabinoid is indeed released from RGCs.

KEYWORDS:

Calcium channels; Cannabinoid CB1 receptor; Inner retina; Synaptic transmission; mEPSCs; mIPSCs

PMID:
25273281
DOI:
10.1007/s00429-014-0908-4
[Indexed for MEDLINE]

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