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Cameron Atkinson, Dao-Qi Zhang; Action potential-dependent calcium influx into ganglion cell photoreceptors mediates retrograde signal transmission to dopaminergic amacrine neurons. Invest. Ophthalmol. Vis. Sci. 2014;55(13):1233.
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We have reported that intrinsically-photosensitive retinal ganglion cells (ipRGCs) appear to drive a subset of dopaminergic amacrine (DA) neurons, providing a novel retrograde signaling pathway that is likely involved in mediating retinal light adaptation (Zhang et al., 2008, 2012; Atkinson et al., 2013). IpRGCs respond to light with a membrane depolarization and an increased action potential (AP) frequency. Here we sought to determine whether the depolarization, increased APs, or both mediate synaptic transmission to DA neurons.
Whole-cell voltage-clamp recordings were made from ipRGCs genetically labeled by GFP and from RFP-labeled DA neurons in whole-mount mouse retinas. Retrograde signaling from ipRGCs to DA neurons was isolated by blocking rod/cone input with L-AP4 in wild-type retinas or by using retinal degeneration 1 (rd1) retinas in which rods and cones have degenerated.
Light-evoked inward currents of DA neurons in rd1 retinas were completely eliminated by the sodium channel blocker tetrodotoxin (TTX; n=4). The same results were observed in 4 DA neurons from wild-type retinas with L-AP4, indicating that TTX appears to block excitatory synaptic transmission from ipRGCs to DA neurons. Interestingly, TTX had no effect on the light-induced inward currents of ipRGCs but eliminated all spontaneous and light-evoked APs (n=2). These results suggest that the TTX blockade of synaptic transmission to DA neurons results from the loss of APs in ipRGCs. Further data suggest that this excitatory signal transmission is primarily calcium dependent because ipRGC signals to DA neurons were almost undetectable in the presence of the non-selective calcium channel blocker cadmium (n=4).
Dendrodendritic synapses (via graded potentials) and recurrent axon collaterals of ipRGCs (via APs) have been proposed as two potential routes of signal transmission from ipRGCs to DA neurons (Zhang et al., 2012). Our physiological data support the latter route in which APs generated in ipRGCs are propagated along recurrent axon collaterals, triggering calcium influx into the axon collateral terminals that may directly synapse onto DA neurons.
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