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Ryan T Maloney, Scott Cruikshank, David M Berson; Properties of retinogeniculate synapses of intrinsically photosensitive retinal ganglion cells. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1614.
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© ARVO (1962-2015); The Authors (2016-present)
Intrinsically Photosensitive Retinal Ganglion Cells (ipRGCs) provide absolute luminance signals to the dorsal lateral geniculate nucleus (dLGN), but how the dLGN intergrates this input is unclear. To explore the relevant synaptic networks, we asessed the effects of selective activation of ipRGC afferents on postsynaptic thalmocortical cells (TCs) in the dLGN.
We made patch-clamp recordings from postsynaptic thalamocortical cells (TCs) in dLGN slices while selectively stimulating ipRGC axons optogenetically. Channelrhodopsin2 was selectively expressed in ipRGCs by injecting a Cre-dependent virus into the eyes of heterozygous melanopsin-Cre mice (Opn4cre/+). The virus was an AAV2 carrying a flexed construct coding for mCherry-Channelrhodopsin fusion protein, driven by the EF1 alpha promoter. Virus was injected neonatally (P7-10) and retinas harvested 4-6 weeks later for recording (age P40-P50). In live coronal slices of the dLGN (300 µm thick), TCs were targeted visually based on proximity to fluorescent mCherry-labeled ipRGC terminals. For each cell, we measured the response to trains of optical ipRGC-activating stimuli both in current clamp and voltage clamp. We varied the clamp potential of the recorded cell (Vhold) to differentiate between excitation and inhibition.
We recorded a total of eight ipRGC-activated TCs in mouse dLGN slices. All cells exhibited both excitatory and inhibitory currents in response to optic activation of local ipRGC axons. The size of these currents varied dramatically. Excitatory currents ranged from 12 to 14,000 pA (measured at Vhold _75mV) and inhibitory currents ranged from 90pA to 1500 pA (Vhold _35mV). All synapses demonstrated synaptic depression and responded to stimuli trains up to a minute long. Additionally, a small subset of synapses (n=2) exhibited prolonged post-stimulus inhibitory responses, lasting up to 30 seconds after stimulation of the ipRGC afferents.
Our results show that the synaptic connection between ipRGCs and TCs of the dLGN is highly variable. This diversity may be linked to the overall diversity of ipRGCs, several subtypes of which are thought to innervate the dLGN. This suggests that ipRGCs may play multiple functional roles in the processing of visual information in the dLGN. In ongoing experiments, we are quantitatively comparing these retinogeniculate synapses with those derived from conventional RGCs.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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