1. Neuroscience
Download icon

Retinal Circuits: How we see the forest and the trees

  1. Jeffrey S Diamond  Is a corresponding author
  1. National Institute of Neurological Disorders and Stroke, United States
Insight
  • Cited 1
  • Views 1,594
  • Annotations
Cite this article as: eLife 2018;7:e41633 doi: 10.7554/eLife.41633

Abstract

Signaling pathways in the retina help us see spatial detail in our visual world.

Main text

Imagine you are walking through an alpine forest on a beautiful fall day, passing a stand of aspen trees with their thin trunks forming a vertical grid before a brilliant backdrop of autumn color. A closer look reveals the horizontal striations in their white bark (Figure 1A,B). This simple, sylvan example highlights how our visual system seamlessly shifts its attention across the broad range of spatial frequencies in the natural world: it can report global shapes, patterns and motion, and also encode fine details, enabling us to see the forest – and the trees.

Figure 1
Download asset Open asset
Processing visual information in the retina.

(A) A stand of aspen trees, seen from a distance, presents primarily vertical lines (Image credit: John Price). (B) Closer inspection reveals primarily horizontal features in the bark of individual trees (Image credit: Peng Chen). (C) Simplified schematic of the retinal circuitry showing the synapses between photoreceptors (top) and bipolar cells, and between bipolar cells and a single ganglion cell. The amacrine cells influence the behavior of the bipolar cells (and the ganglion cells). (D) Neurotransmitter release by bipolar cells (y-axis) versus the membrane potential of these cells. Bipolar cells inhabit one of three release regimes: quiescent (blue), when visual stimulation is insufficient to evoke release; linear (red), when release is proportional to the stimulus; and rectified (gold), when only positive stimuli evoke release. (E) Schematic showing a checkerboard stimulus presented to a 2 × 2 array of bipolar cells. (F) The change in the membrane potential (y-axis) over time (x-axis) of each bipolar cell depends on whether it receives a positive stimulus (2 and 3) or a negative stimulus (1 and 4) from the checkerboard. (G) The release of neurotransmitters from the four bipolar cells and the resulting response in the ganglion cell (bottom) depend on the release regime occupied by the bipolar cell (see main text).

One might expect that such a sophisticated system would require this information to be sent to 'higher' visual centers in the brain for processing. However, much of this processing is actually carried out at a relatively 'low' level by the neurons in the retina (Hochstein and Shapley, 1976; Demb et al., 1999; Schwartz et al., 2012; Grimes et al., 2014; Turner and Rieke, 2016). Now, in eLife, Maxwell Turner and Fred Rieke of the University of Washington, and Gregory Schwartz of Northwestern University, report how circuits in the retina fine-tune their spatial sensitivity in response to the surrounding visual world (Turner et al., 2018).

Neurons communicate with each other by releasing signaling molecules called neurotransmitters into the synaptic gaps between them. In the retina, visual signals in the form of slow, graded changes in membrane potential are transmitted from photoreceptors (the cells that actually detect the light we see) to bipolar cells and then to ganglion cells (Figure 1C). The release of neurotransmitters from bipolar cells into a synapse depends on the value of the membrane potential of the neuron relative to the activation range of the calcium ion channels that trigger the release (Figure 1D). There are three different regimes: the 'quiescent' regime, in which only a very strong positive stimulus will evoke release; the 'rectified' regime, in which a positive stimulus will evoke release, but a negative stimulus will not; and the 'linear' regime, in which a positive stimulus will lead to an increase in release, and a negative stimulus will lead to a decrease. Many of the synapses formed by bipolar cells operate in the 'rectified' regime.

Turner et al. studied how visual signals are transmitted from a number of bipolar cells to a single ganglion cell. This transmission depends on which regime the bipolar cells are in, particularly when the intensity of the visual image being transmitted varies across the receptive field of the ganglion cells (Croner and Kaplan, 1995).

Suppose that the bipolar cells in a 2 × 2 array are stimulated independently by a checkerboard image, with two cells receiving a positive stimulus and two receiving a negative stimulus (Figure 1E,F). If the bipolar cells are quiescent, the stimuli will not evoke a release from any of the four cells, and hence no signal will be transmitted to the ganglion cell. Likewise, if the bipolar cells are in the 'linear' regime, the release of neurotransmitters from two of the cells will increase, and the release from two will decrease, thus cancelling each other out, so the signal being transmitted to the ganglion cell will not change. Linear responses can, therefore, diminish the responses of the ganglion cells to higher spatial frequencies. However, if the bipolar cells are in the 'rectified' regime, only the two positively stimulated bipolar cells will release a neurotransmitter, enabling the ganglion cells to respond (Figure 1G; Enroth-Cugell and Robson, 1966).

Another set of cells in the inner retina, the amacrine cells, are also involved regulating the release of neurotransmitters by bipolar cells and thus fine-tuning the information transferred to ganglion cells. In particular, the amacrine cells contribute to the 'center-surround' organization of the receptive fields of ganglion cells: put simply, this means that if a ganglion cell is excited by a stimulus in the center of its receptive field, a similar stimulus in the surrounding area will be inhibitory.

Turner et al. show that ‘surround inhibition’ can influence the spatial sensitivity of the ganglion cells by shifting the bipolar cells from one release regime to another. Strong surround inhibition pushes bipolar cells toward quiescence, limiting responses to center stimuli. Conversely, surround stimuli of the opposite polarity to that of the center decreases inhibition in the surround, pushing the bipolar cells into their linear regime. As a result, contrasting details in the center cancel each other, reducing the ganglion cells’ spatial sensitivity. This proves useful when visual features change abruptly on a larger spatial scale, and encoding global contrast or motion takes temporary precedence over the finer details.

In our spatially correlated natural world, however, the luminance of the center and surround are often similar, so that bipolar cells occupy their rectified regime, thereby maximizing the sensitivity of the ganglion cells to higher spatial frequencies (Field, 1987). Notably, these changes can occur quickly, enabling the circuit to adapt in real time to changing visual conditions.

The work by Turner et al. and others has certainly expanded our appreciation for the remarkable versatility and computational power of this thin, transparent sheet of neurons that lines the back of the eye (Gollisch and Meister, 2010). The retinal circuitry has revealed itself as a dense forest of connected trees that holds many more secrets yet to be discovered.

References

Article and author information

Author details

  1. Jeffrey S Diamond

    Jeffrey S Diamond is in the Synaptic Physiology Section, National Institute of Neurological Disorders and Stroke, Bethesda, United States
    For correspondence
    diamondj@ninds.nih.gov
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1770-2629

Publication history

  1. Version of Record published: October 12, 2018 (version 1)

Copyright

© 2018, Diamond

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,594
    Page views
  • 158
    Downloads
  • 1
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Categories and tags

Research organism

Further reading

    1. Neuroscience

    Receptive field center-surround interactions mediate context-dependent spatial contrast encoding in the retina

    Maxwell H Turner et al.
    Research Article Updated

    Antagonistic receptive field surrounds are a near-universal property of early sensory processing. A key assumption in many models for retinal ganglion cell encoding is that receptive field surrounds are added only to the fully formed center signal. But anatomical and functional observations indicate that surrounds are added before the summation of signals across receptive field subunits that creates the center. Here, we show that this receptive field architecture has an important consequence for spatial contrast encoding in the macaque monkey retina: the surround can control sensitivity to fine spatial structure by changing the way the center integrates visual information over space. The impact of the surround is particularly prominent when center and surround signals are correlated, as they are in natural stimuli. This effect of the surround differs substantially from classic center-surround models and raises the possibility that the surround plays unappreciated roles in shaping ganglion cell sensitivity to natural inputs.

    1. Neuroscience

    A transient postnatal quiescent period precedes emergence of mature cortical dynamics

    Soledad Dominguez et al.
    Research Article

    Mature neural networks synchronize and integrate spatiotemporal activity patterns to support cognition. Emergence of these activity patterns and functions is believed to be developmentally regulated, but the postnatal time course for neural networks to perform complex computations remains unknown. We investigate the progression of large-scale synaptic and cellular activity patterns across development using high spatiotemporal resolution in vivo electrophysiology in immature mice. We reveal that mature cortical processes emerge rapidly and simultaneously after a discrete but volatile transition period at the beginning of the second postnatal week of rodent development. The transition is characterized by relative neural quiescence, after which spatially distributed, temporally precise, and internally organized activity occurs. We demonstrate a similar developmental trajectory in humans, suggesting an evolutionarily conserved mechanism that could facilitate a transition in network operation. We hypothesize that this transient quiescent period is a requisite for the subsequent emergence of coordinated cortical networks.

    1. Neuroscience

    A locomotor neural circuit persists and functions similarly in larvae and adult Drosophila

    Kristen Lee, Chris Q Doe
    Research Advance Updated

    Individual neurons can undergo drastic structural changes, known as neuronal remodeling or structural plasticity. One example of this is in response to hormones, such as during puberty in mammals or metamorphosis in insects. However, in each of these examples, it remains unclear whether the remodeled neuron resumes prior patterns of connectivity, and if so, whether the persistent circuits drive similar behaviors. Here, we utilize a well-characterized neural circuit in the Drosophila larva: the moonwalker descending neuron (MDN) circuit. We previously showed that larval MDN induces backward crawling, and synapses onto the Pair1 interneuron to inhibit forward crawling (Carreira-Rosario et al., 2018). MDN is remodeled during metamorphosis and regulates backward walking in the adult fly. We investigated whether Pair1 is remodeled during metamorphosis and functions within the MDN circuit during adulthood. We assayed morphology and molecular markers to demonstrate that Pair1 is remodeled during metamorphosis and persists in the adult fly. MDN-Pair1 connectivity is lost during early pupal stages, when both neurons are severely pruned back, but connectivity is re-established at mid-pupal stages and persist into the adult. In the adult, optogenetic activation of Pair1 resulted in arrest of forward locomotion, similar to what is observed in larvae. Thus, the MDN-Pair1 neurons are an interneuronal circuit – a pair of synaptically connected interneurons – that is re-established during metamorphosis, yet generates similar locomotor behavior at both larval and adult stages.