Synaptic circuits for irradiance coding by intrinsically photosensitive retinal ganglion cells

Abstract

We have explored the synaptic networks responsible for the unique capacity of intrinsically photosensitive retinal ganglion cells (ipRGCs) to encode overall light intensity. This luminance signal is crucial for circadian, pupillary and related reflexive responses light. By combined glutamate-sensor imaging and patch recording of postsynaptic RGCs, we show that the capacity for intensity-encoding is widespread among cone bipolar types, including OFF types.Nonetheless, the bipolar cells that drive ipRGCs appear to carry the strongest luminance signal.By serial electron microscopic reconstruction, we show that Type 6 ON cone bipolar cells are the dominant source of such input, with more modest input from Types 7, 8 and 9 and virtually none from Types 5i, 5o, 5t or rod bipolar cells. In conventional RGCs, the excitatory drive from bipolar cells is high-pass temporally filtered more than it is in ipRGCs. Amacrine-to-bipolar cell feedback seems to contribute surprisingly little to this filtering, implicating mostly postsynaptic mechanisms. Most ipRGCs sample from all bipolar terminals costratifying with their dendrites, but M1 cells avoid all OFF bipolar input and accept only ectopic ribbon synapses from ON cone bipolar axonal shafts. These are remarkable monad synapses, equipped with as many as a dozen ribbons and only one postsynaptic process.

Direction selectivity in retinal bipolar cell axon terminals

“…To anatomically confirm the involvement of starburst and wide-field amacrine cells in the direction-selectivity computation of bipolar cells, we used a serial block-face electron microscopy (SBEM) dataset ( Ding et al., 2016 ). We reconstructed a T7 bipolar cell that formed synapses with ON-OFF DSGCs ( Figure 5 ) ( Ding et al., 2016 ; Sabbah et al., 2018 ; Sethuramanujam et al., 2021 ), traced all synapses from amacrine cells, and reconstructed the amacrine cell dendritic/axonal processes ( Figure S5 ). The reconstructed amacrine cells fell into two categories: wide-field cells with long axon-like processes (31%) and non-wide-field cells with highly branched processes (69%) ( Figures 5 A–5D; Figures S6 A–S6C).…”

Synapse-specific direction selectivity in retinal bipolar cell axon terminals

“…We first reconstructed all ON and OFF bipolar cells that formed synapses with ON-OFF DSGC cells (fig. S5, A to D) ( 13, 24, 25 ), then focused on one of the reconstructed T7 bipolar cells (fig. S5E) for further tracing of synapses from amacrine cells onto this T7 bipolar cell.…”

Luxotonic signals in human prefrontal cortex as a possible substrate for effects of light on mood and cognition

“…2A, 3). ipRGCs responses in humans (Mure et al, 2019), as well as in the mouse (Estevez et al, 2012; Sabbah et al, 2018; Schmidt and Kofuji, 2009; Wong, 2012), persist throughout the duration of the stimulus and even after light offset, with the post-stimulus response duration increasing with luminance. Thus, the similarity in light-evoked activity in ipRGCs and the human PFC may suggest a contribution of ipRGCs’ light responses to PFC activation.…”

“…Bright light affects decision-making and working memory, key functions of the prefrontal cortex 12–15 . These effects are thought to depend upon a specialized output channel of the retina dedicated to a stable representation of environmental illumination – a luminance signal 16–19 . This retinal output signal arises from intrinsically photosensitive retinal ganglion cells (ipRGCs), a rare class of output neuron that is autonomously sensitive to light by virtue of its expression of the photopigment melanopsin 20,21 .…”

“…Interestingly, bright light was also found to affect decision-making and working memory, both being key functions of the prefrontal cortex (PFC) (Daneault et al, 2018; Kretschmer et al, 2012; Vandewalle et al, 2007; Xu and Labroo, 2014). These luminance-related effects are thought to depend upon a specialized output channel of the retina dedicated to a stable representation of environmental illumination, constituting a luminance signal (Sabbah et al, 2018; Schmidt and Kofuji, 2009; Wong, 2012). However, the origin of the specific luminance signal acting in the PFC has yet to be identified.…”