Purchase this article with an account.
Cameron L Prigge, Dao-Qi Zhang; Pre- and post-synaptic mechanisms of signal transmission from ganglion cell photoreceptors to dopaminergic amacrine neurons. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):4375.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
We have previously reported that axon collaterals of intrinsically photosensitive retinal ganglion cells (ipRGCs) form a novel retrograde pathway with dopaminergic amacrine (DA) neurons in the retina (Zhang et al., 2008; Atkinson and Zhang, 2014), yet the underlying synaptic mechanisms are not well understood. Here we sought to determine the pre- and post-synaptic mechanisms involved.
Genetically labeled DA neurons and ipRGCs were recorded in whole mount retinas using the whole-cell voltage-clamp technique. IpRGC input to DA neurons was isolated in retinal degeneration 1 mice in which rods and cones have degenerated or in wild type mice with rod/cone input blocked by L-AP4.
3 s of 470-nm light evoked ipRGC-mediated inward current of DA neurons that was profoundly attenuated by both low extracellular calcium (-65%; p<0.01, n=8) and cadmium (-79%; p<0.001, n=9), suggesting signal transmission is calcium dependent. However, cadmium did not suppress light-induced activity of ipRGCs or kainate-induced currents of DA neurons, indicating cadmium blocks calcium channels on presynaptic axon collaterals of ipRGCs to suppress signal transmission to DA neurons. Our data further showed that N-type calcium channels are primarily involved because blockade of N-type calcium channels with ω-conotoxin GVIA reduced the inward current by 47% (p<0.05; n=7); no other calcium channel (L-, P/Q-, R-, or T-types) antagonist had a significant effect. In addition, the application of ACET, a kainate receptor antagonist, did not significantly affect the DA neuron inward current (n=4); however, co-application of the AMPA/kainate receptor antagonist, CNQX, completely abolished signal transmission (n=4), suggesting signal transmission is mediated by postsynaptic AMPA receptors. The AMPA-mediated component of the DA neuron light response was found to be mediated by non-rectifying, calcium-impermeable AMPA receptors.
Our results provide insights into the pre- and post-synaptic mechanisms of retrograde signal transmission from ipRGCs to DA neurons. The retrograde feedback loop formed by ipRGCs and DA neurons can modulate all levels of retinal circuitry through the volume transmission of dopamine.
This PDF is available to Subscribers Only