Local Signals in Mouse Horizontal Cell Dendrites

Abstract

The mouse retina contains a single type of horizontal cell, a GABAergic interneuron that samples from all cone photoreceptors within reach and modulates their glutamatergic output via parallel feedback mechanisms. Because horizontal cells form an electrically coupled network, they have been implicated in global signal processing, such as large-scale contrast enhancement. Recently, it has been proposed that horizontal cells can also act locally at the level of individual cone photoreceptors. To test this possibility physiologically, we used two-photon microscopy to record light stimulus-evoked Ca signals in cone axon terminals and horizontal cell dendrites as well as glutamate release in the outer plexiform layer. By selectively stimulating the two mouse cone opsins with green and UV light, we assessed whether signals from individual cones remain isolated within horizontal cell dendritic tips or whether they spread across the dendritic arbor. Consistent with the mouse's opsin expression gradient, we found that the Ca signals recorded from dendrites of dorsal horizontal cells were dominated by M-opsin and those of ventral horizontal cells by S-opsin activation. The signals measured in neighboring horizontal cell dendritic tips varied markedly in their chromatic preference, arguing against global processing. Rather, our experimental data and results from biophysically realistic modeling support the idea that horizontal cells can process cone input locally, extending the classical view of horizontal cell function. Pharmacologically removing horizontal cells from the circuitry reduced the sensitivity of the cone signal to low frequencies, suggesting that local horizontal cell feedback shapes the temporal properties of cone output.

Retinal horizontal cells use different synaptic sites for global feedforward and local feedback signaling

“…For the checkerboard noise, which is a spatially maximally uncorrelated stimulus, the result 258 was different: The average correlation between voltage signals in tips was rather low (0.25 ± 0.14), 259 confirming our previous results (Chapot et al 2017). In contrast, the average correlation between 260 voltage signals in bulbs was much higher (0.71 ± 0.19) and so was the correlation between bulb signal 261 and the average over the tip signals (0.80 ± 0.10) ( Fig.…”

“…Whether the size and efficiency of 361 synaptic contacts is different and whether or how synaptic scaling is implemented for ON-CBC and 362 HC contacts has to be addressed in a future functional study. A recent study showed that, based on their thin diameter and high resistance, the fine HC 373 dendritic tips are optimized for generation of local cone-specific feedback and to a lesser extent for 374 lateral propagation of electrical signals (Chapot et al 2017). However, the extent to which the 375 feedback to cones is global or local strongly depends on the presented visual stimulus.…”

Cellular and molecular mechanisms of photoreceptor tuning for prey capture in larval zebrafish

“…7g). This strongly indicated that there was no glutamate spill-over between neighbouring ROIs (see also discussions in refs (Chapot et al, 2017b;Franke et al, 2017;James et al, 2019)). Our approach therefore allowed recording UV-cone driven glutamate in the live eye at single pedicle resolution.…”

“…To address this question, we established optical glutamate recordings from single cones in the live eye by expressing the fluorescent glutamate biosensor SFiGluSnFR (Marvin et al, 2018) in postsynaptic HCs. HCs contact cones at specialised invaginations that are tightly sealed against the surrounding extracellular matrix (Chapot et al, 2017b;Regus-Leidig and Brandstätter, 2012) , meaning that their dendrites can act as highly specific and spatially restricted glutamate antennas (Chapot et al, 2017b). As a population, HCs contact all four types of cones in the zebrafish eye (Klaassen et al, 2016;Li et al, 2009;Yoshimatsu et al, 2014), meaning that only a subset of HC dendritic signals correspond to synaptic release from UVcones.…”

“…Retinal and central wiring for prey capture. The region-specific differences in UV-cone function present the first preprocessing steps to detect prey and predators already at the visual system's first synapse (Baden et al, 2013b;Chapot et al, 2017b). However, how these signals are used by retinal and brain networks for robust extraction of such behaviourally crucial information remains an open question.…”