General features of inhibition in the inner retina

Abstract

Visual processing starts in the retina. Within only two synaptic layers, a large number of parallel information channels emerge, each encoding a highly processed feature like edges or the direction of motion. Much of this functional diversity arises in the inner plexiform layer, where inhibitory amacrine cells modulate the excitatory signal of bipolar and ganglion cells. Studies investigating individual amacrine cell circuits like the starburst or A17 circuit have demonstrated that single types can possess specific morphological and functional adaptations to convey a particular function in one or a small number of inner retinal circuits. However, the interconnected and often stereotypical network formed by different types of amacrine cells across the inner plexiform layer prompts that they should be also involved in more general computations. In line with this notion, different recent studies systematically analysing inner retinal signalling at a population level provide evidence that general functions of the ensemble of amacrine cells across types are critical for establishing universal principles of retinal computation like parallel processing or motion anticipation. Combining recent advances in the development of indicators for imaging inhibition with large-scale morphological and genetic classifications will help to further our understanding of how single amacrine cell circuits act together to help decompose the visual scene into parallel information channels. In this review, we aim to summarise the current state-of-the-art in our understanding of how general features of amacrine cell inhibition lead to general features of computation.

Keywords: GABA; amacrine cell; computation; glycine; inhibition; neuronal network; retina; vision.

Figure 1. Organisation of the amacrine cell network in the inner retina

A, in the retina, photoreceptors (PRs, purple) transduce the visual input into an electrical signal and feed into bipolar cells (BCs, green) that provide input to the retina's output neurons, the retinal ganglion cells (RGCs, blue). This vertical excitatory pathway is extensively modulated by inhibitory amacrine cells (ACs) in the inner retina. Here, wide‐field ACs (red) mainly transfer information laterally within individual synaptic layers, while small‐field ACs (orange) predominantly mediate vertical signalling across synaptic layers. Arrows indicate main signal flow. HC, horizontal cells (yellow). B, ACs form a complex and dense synaptic network in the inner plexiform layer. In mammals, wide‐field ACs use GABA as neurotransmitter (light blue vesicles), while small‐field ACs use glycine (purple vesicles). Bipolar cells use glutamate (green vesicles). C, ACs provide inhibitory inputs to BC axon terminals (presynaptic inhibitory inputs), RGC dendrites (postsynaptic inhibitory inputs) and other ACs (serial inhibitory inputs).

Figure 2. Example of a general function of amacrine cells

A, a local stimulus (100 μm diameter, yellow) mainly activates retinal pathways directly beneath the stimulus including PRs and BCs as well as small‐field ACs. The glutamatergic output of individual BCs in response to such a local light step (left) and contrast flicker (right), is nearly independent of the specific BC type recorded from (of the same polarity) – here exemplarily shown for two On (CBC9 and CBC6) and Off (CBC1 and CBC3a) BC types (Franke et al. 2017). The last row of traces represents an overlay of the previous two rows. Colour intensity used to indicate expected stimulus‐driven activity level of individual neurons. B, full‐field stimulation (600 μm diameter) additionally recruits wide‐field ACs that provide inhibitory GABAergic inputs to BC axon terminals and AC dendrites. This lateral inhibition decorrelates the BC responses, thereby increasing the functional diversity across BC types (Franke et al. 2017). Because the response diversification is observed for all BC types, which receive inputs from different AC types, this effect illustrates an example of a general role of ACs in inner retinal signalling.