Purchase this article with an account.
Shengnan Qiao, Yong-Mei Zhong, Dao-Qi Zhang; Cone photoreceptors mediate dopaminergic amacrine neuron activity via multiple neural pathways. Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):3228.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Dopamine is a key neurotransmitter in the retina and its release from dopaminergic amacrine (DA) neurons appears to be regulated by three classes of photosensitive cells: rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs). However, the neural pathways that convey electrical signals from these photoreceptors to DA neurons are still unclear. Here we report that cones regulate DA neuron activity via four distinct neural pathways in the mouse retina.
Genetically labeled DA neurons were recorded in flat-mount retinas of mice that lack rod and melanopsin function using the whole-cell voltage-clamp technique.
DA neurons recorded at -70 mV exhibited inward current at light onset to 3 s of 470 nm light and this inward current was eliminated by the ON pathway blocker L-AP4 (n=8), indicating that DA neurons are excited by rods and cones via ON bipolar cells. In 2 out of 8 neurons, the sodium channel blocker TTX, which selectively eliminates signal transmission from ipRGCs to DA neurons, reduced the inward current amplitude and accelerated the current kinetics, suggesting DA neurons also receive indirect input from ON bipolar cells via ipRGCs. In addition, 7 out of 8 DA neurons had responses (inward or outward current) at light offset. The OFF responses persisted with L-AP4 but were abolished with ACET, an OFF pathway blocker or the co-application of strychnine and GABAzine. These results indicate DA neurons receive inhibitory input from amacrine cells that are driven by rods and cones via OFF bipolar cells. Furthermore, 5 DA neurons exhibited either inward current (n=3) or outward current (n=2) ~1 s after light onset in the presence of L-AP4. These responses were not affected by ACET indicating that they were not mediated by OFF bipolar cells. However, the responses were blocked by strychnine, indicative of input from glycinergic amacrine cells.
Our results suggest DA neurons are excited by cones directly via ON bipolar cells or indirectly through ipRGCs and are negatively regulated by inhibitory amacrine cells that are either driven by OFF bipolar cells or by an unidentified cell type. The parallel excitatory and inhibitory inputs to DA neurons and their interactions can efficiently regulate dopamine release to optimize visual signaling to prevailing illumination.
This PDF is available to Subscribers Only