http://www.cell.com/article/S0960982222004882/pdf

Distinct inhibitory pathways control velocity and directional tuning in the mouse retina

The asymmetric summation of kinetically distinct glutamate inputs across the dendrites of retinal “starburst” amacrine cells is proposed to underlie their direction selective properties, but experimentally verifying input kinetics has been a challenge. Here, we used two-photon glutamate sensor (iGluSnFR) imaging to directly measure the input kinetics across individual starburst dendrites. We found that signals measured from proximal dendrites were relatively sustained compared to those measured from distal dendrites. These differences were observed across a range of stimulus sizes and appeared to be shaped mainly by excitatory rather than inhibitory network interactions. Temporal deconvolution analysis suggests that the steady-state vesicle release rate was ∼ 3 times larger at proximal sites compared to distal sites. Using a connectomics-inspired computational model, we demonstrate that input kinetics play an important role in shaping direction selectivity at low stimulus velocities. Together, these results provide direct support for the ‘space-time wiring’ model for direction selectivity.

Spatiotemporal properties of glutamate input support direction selectivity in the dendrites of retinal starburst amacrine cells

Although gap junctional coupling in the developing retina is important for the maturation of neuronal networks, its role in the development of individual neurons remains unclear. Therefore, we herein investigated whether gap junctional coupling by starburst amacrine cells (SACs), a key neuron for the formation of direction selectivity, occurs during the developmental stage in the mouse retina. Neurobiotin-injected SACs coupled with many neighboring cells before eye-opening. The majority of tracer-coupled cells were retinal ganglion cells, and tracer coupling was not detected between SACs. The number of tracer-coupled cells significantly decreased after eye-opening and mostly disappeared by postnatal day 28 (P28). Membrane capacitance (Cm), an indicator of the formation of electrical coupling with gap junctions, was larger in SACs before than after eye-opening. The application of meclofenamic acid, a gap junction blocker, reduced the Cm of SACs. Gap junctional coupling by SACs was regulated by dopamine D1 receptors before eye-opening. In contrast, the reduction in gap junctional coupling after eye-opening was not affected by visual experience. At the mRNA level, 4 subtypes of connexins (23, 36, 43, and 45) were detected in SACs before eye-opening. Connexin 43 expression levels significantly decreased after eye-opening. These results indicate that gap junctional coupling by SACs occurs during the developmental period and suggest that the elimination of gap junctions proceeds with the innate system.

/pdf/starburst-amacrine-cells-form-gap-junctions-in-the-early-42reee52.pdf

Starburst amacrine cells form gap junctions in the early postnatal stage of the mouse retina

The sensory periphery is responsible for detecting ethologically relevant features of the external world, using compact, predominantly feedforward circuits. Visual motion is a particularly prevalent sensory feature, the presence of which can be a signal to enact diverse behaviors ranging from gaze stabilization reflexes, to predator avoidance or prey capture. To understand how the retina constructs the distinct neural representations required for these diverse behaviors, we investigated two circuits responsible for encoding different aspects of image motion: ON and ON-OFF direction selective ganglion cells (DSGCs). Using a combination of 2-photon targeted whole cell electrophysiology, pharmacology, and conditional knockout mice, we show that distinct inhibitory pathways independently control tuning for motion velocity and motion direction in these two cell types. We further employ dynamic clamp and numerical modeling techniques to show that asymmetric inhibition provides a velocity-invariant mechanism of directional tuning, despite the strong velocity dependence of classical models of direction selectivity. We therefore demonstrate that invariant representations of motion features by inhibitory interneurons act as computational building blocks to construct distinct, behaviorally relevant signals at the earliest stages of the visual system.

/pdf/distinct-inhibitory-pathways-control-velocity-and-1kui9csj.pdf

Distinct Inhibitory Pathways Control Velocity and Directional Tuning in the Retina

The retinal neural circuit is intricately wired for efficient processing of visual signals. This is well-supported by the specialized connections between retinal neurons at both the functional and ultrastructural levels. Through 3D electron microscopic (EM) reconstructions of retinal neurons and circuits we have learnt much about the specificities of connections within the retinal layers including new insights into how retinal neurons establish connections and perform sophisticated visual computations. This mini-review will summarize the retinal circuitry and provide details about the novel insights EM connectomics has brought into our understanding of the retinal circuitry. We will also discuss unresolved questions about the retinal circuitry that can be addressed by EM connectomics in the future.

https://www.frontiersin.org/articles/10.3389/fopht.2023.1168548/pdf

New insights into retinal circuits through EM connectomics: what we have learnt and what remains to be learned

Retinal ON starburst amacrine cells (SACs) play a critical role in computing stimulus direction, partly in service of image stabilization by optokinetic nystagmus. ON SAC responses are sculpted by rich GABAergic innervation, mostly from neighbouring SACs. Surprisingly, however, we find that glycinergic narrow field amacrine cells (NACs) serve as their dominant source of inhibition during sustained activity. Although NAC inputs constitute only ~5% of inhibitory synapses to ON SACs, their distinct input patterns enable them to drive glycine inhibition during the both light increments and decrements. NAC to ON SAC inhibition appears to be mediated by ultra-slow non-canonical glycine receptors containing the α4 subunit, which effectively summate during repetitive stimulation. Glycinergic inhibition strongly decreases the output gain of the SACs, ensuring that their direction-selective output is maintained over their operating range. These results reveal an unexpected role for glycinergic pathways and receptor kinetics in modulating direction selectivity in the retina.

https://biorxiv.org/content/10.1101/2021.05.03.442480v1.full.pdf

Jain

Papers

Gain control by sparse, ultra-slow glycinergic synapses