Retinal ganglion cell maps in the brain: implications for visual processing

doi:10.1016/j.conb.2013.08.006

Current Opinion in Neurobiology

Volume 24, February 2014, Pages 133-142

https://doi.org/10.1016/j.conb.2013.08.006 Get rights and content

Highlights

•
The retina conveys a rich set of information about the content of the visual world to the brain.
•
Genetic tools are starting to reveal ‘labeled lines’ extending from the retina to visual targets in the brain that control specific behaviors.
•
The dorsal lateral geniculate nucleus harbors cell types tuned for directional motion and orientation features that may arise from the retina.
•
Genetic and imaging studies are starting to provide a window into how retinal maps are kept separate or combined within the brain.

Everything the brain knows about the content of the visual world is built from the spiking activity of retinal ganglion cells (RGCs). As the output neurons of the eye, RGCs include ∼20 different subtypes, each responding best to a specific feature in the visual scene. Here we discuss recent advances in identifying where different RGC subtypes route visual information in the brain, including which targets they connect to and how their organization within those targets influences visual processing. We also highlight examples where causal links have been established between specific RGC subtypes, their maps of central connections and defined aspects of light-mediated behavior and we suggest the use of techniques that stand to extend these sorts of analyses to circuits underlying visual perception.

Introduction

Over 50 years ago, Lettvin et al. published the seminal paper ‘What the Frog's Eye Tells the Frog's Brain’ [1]. Lettvin described the many elaborate features encoded by the output neurons of the eye — the retinal ganglion cells (RGCs), such as edges, looming objects, or ‘bug detectors’ that respond best to small stimuli moving against a stationary background. The broad textbook model of vision nevertheless became that RGCs have simple center-surround receptive fields that are combined within the brain to generate more complex feature representations [2]. This certainly is the case for some RGCs and visual channels [3, 4, 5]. However, Lettvin also had it right: regardless of whether you examine the eye of a fish, mouse, rat, rabbit, monkey or human, you’ll find ∼20 distinct subtypes of RGCs, each responding best to a specific, often highly specialized arrangement of light and dark in the visual environment [6, 7•, 8]. For example, some RGCs respond best to specific directions of motion [9, 10, 11] or orientations [12, 13, 14] and still others are suppressed by contrast [15] or signal the presence of looming stimuli [16]. A complete cataloging of the features encoded by different RGC subtypes is ongoing, but one thing is clear: RGCs are primed to deliver a rich set of visual information to the brain. In mammals there are also more than two-dozen brain areas that receive direct input from RGCs. Thus, the following crucial questions arise:

1.
Where does each RGC subtype project to in the brain?
2.
How are the visual signals encoded by different RGC subtypes integrated by local circuits within their targets?
3.
How does the parallel organization of retinal maps influence visual perception and behavior?

In the following sections, we address recent progress toward answering these questions. We focus on four different eye-to-brain pathways, each serving a dedicated aspect of visual processing.

Section snippets

Intrinsically photosensitive RGCs: linking irradiance detectors to brain nuclei controlling specific non-image-forming behaviors

One of the great ongoing successes in the effort to link specific RGC subtypes and their maps in the brain to well defined visual behaviors comes from the study of intrinsically photosensitive RGCs (ipRGCs). All ipRGCs respond directly to light due to their expression of melanopsin photopigment [17, 18, 19, 20]. Genetic labeling of ipRGCs from the melanopsin locus enabled selective mapping of ipRGC axonal projections within the brain and thereby revealed their two major targets: the

The superior colliculus contains functionally distinct parallel visual maps

The superior colliculus (SC) is a large multimodal structure involved in directing the head and eyes to particular locations in visual space [35]. Input from the retina is delivered to the superficial-most layers of the SC where it is topographically mapped and aligned with the auditory and somatosensory maps that reside in deeper layers [36]. Recently, there has been a surge in understanding about how different RGCs and the information they encode are mapped in the SC. In large part these

Cell-type-specific targeting of RGCs in the lateral geniculate nucleus

The recent advent of genetic tools for labeling specific RGC subtypes has greatly expanded understanding of how different visual channels are organized within the most famous mammalian retinorecipient target — the dorsal lateral geniculate nucleus (dLGN). Studies used transgenic labeling of specific RGC subtypes to demonstrate that the mouse dLGN contains at least two broad categories of functionally distinct retinal maps: a laminar map of direction selective RGC (DSGC) axons that resides

Mapping direction selective retinal inputs to brain areas that control image-stabilization

As the eyes and head move, images slip on the retina; left unchecked this would blur the image of the visual scene. A specialized set of direction selective RGCs and central targets together called the accessory optic system (AOS) generate reflexive eye movements that compensate for retinal slip [70, 71, 72•]. Consequently, the AOS is a powerful model for probing how the mapping of DSGCs relates to visual behavior. Classic work in rabbits [70] showed that the AOS consists of On-DSGCs that

Perspectives

Here we reviewed recent advances in understanding how different RGCs map visual features to the brain. In some cases such as the ipRGCs, those maps resemble ‘labeled lines’, whereas in other cases, such as the retinal inputs to the SC, they are poised to converge in a combinatorial pattern. Understanding the relevance of this convergence to visual processing and perception represents an important unmet challenge. For example, does the combined directional tuning of dLGN neurons simply mirror

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

• of special interest
•• of outstanding interest

Acknowledgements

We thank Maureen Eztevez, David Berson, Jianhua Cang and Cris Niell and members of the Huberman Lab for helpful comments. Support was provided by Knights Templar Eye Foundation (O.S.D) and by NIH R01 EY022157-01, The McKnight Endowment Fund for Neuroscience and the Pew Charitable Trusts (A.D.H).

References (82)

S.P. Brown et al.
Receptive field microstructure and dendritic geometry of retinal ganglion cells
Neuron
(2000)
H.B. Barlow et al.
Selective sensitivity to direction of movement in ganglion cells of the rabbit retina
Science
(1963)
B. Sivyer et al.
Uniformity detector retinal ganglion cells fire complex spikes and receive only light-evoked inhibition
Proc Natl Acad Sci U S A
(2010)
A.D. Güler et al.
Melanopsin cells are the principal conduits for rod–cone input to non-image-forming vision
Nature
(2008)
Y. Zhang et al.
The most numerous ganglion cell type of the mouse retina is a selective feature detector
Proc Natl Acad Sci U S A
(2012)
L. Wang et al.
Visual receptive field properties of neurons in the superficial superior colliculus of the mouse
J Neurosci
(2010)
J.P. Gabriel et al.
Layer-specific targeting of direction-selective neurons in the zebrafish optic tectum
Neuron
(2012)
X. Zhao et al.
Orientation-selective responses in the mouse lateral geniculate nucleus
J Neurosci
(2013)
D.L. Stewart et al.
Receptive-field characteristics of lateral geniculate neurons in the rabbit
J Neurophysiol
(1971)
S.K. Cheong et al.
Cortical-like receptive fields in the lateral geniculate nucleus of marmoset monkeys
J Neurosci
(2013)

W.R. Levick et al.

Rabbit lateral geniculate nucleus: sharpener of directional information

Science

(1969)

O.S. Dhande et al.

Development of single retinofugal axon arbors in normal and beta2 knock-out mice

J Neurosci

(2011)

J.Y. Lettvin et al.

What the frog's eye tells the frog's brain

Proc Inst Radio Eng

(1959)

D.H. Hubel et al.

Receptive fields, binocular interaction and functional architecture in the cat's visual cortex

J Physiol

(1962)

W.M. Usrey et al.

Specificity and strength of retinogeniculate connections

J Neurophysiol

(1999)

B. Chapman et al.

Relation of cortical cell orientation selectivity to alignment of receptive fields of the geniculocortical afferents that arborize within a single orientation column in ferret visual cortex

J Neurosci

(1991)

D.M. Dacey

Origins of perception: retinal ganglion cell diversity and the creation of parallel visual pathways

D.M. Berson

Retinal ganglion cell types and their central projections

R.H. Masland

The neuronal organization of the retina

Neuron

(2012)

C.W. Oyster et al.

Direction-selective units in rabbit retina: distribution of preferred directions

Science

(1967)

D.I. Vaney et al.

Direction selectivity in the retina: symmetry and asymmetry in structure and function

Nat Rev Neurosci

(2012)

S.A. Bloomfield

Orientation-sensitive amacrine and ganglion cells in the rabbit retina

J Neurophysiol

(1994)

W.R. Levick et al.

Analysis of orientation bias in cat retina

J Physiol

(1982)

C.L. Passaglia et al.

Orientation sensitivity of ganglion cells in primate retina

Vision Res

(2002)

T.A. Münch et al.

Approach sensitivity in the retina processed by a multifunctional neural circuit

Nat Neurosci

(2009)

S. Hattar et al.

Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity

Science

(2002)

D.M. Berson et al.

Phototransduction by retinal ganglion cells that set the circadian clock

Science

(2002)

T.M. Schmidt et al.

Melanopsin-positive intrinsically photosensitive retinal ganglion cells: from form to function

J Neurosci

(2011)

M.T. Do et al.

Intrinsically photosensitive retinal ganglion cells

Physiol Rev

(2010)

S. Hattar et al.

Central projections of melanopsin-expressing retinal ganglion cells in the mouse

J Comp Neurol

(2006)

J.L. Ecker et al.

Melanopsin-expressing retinal ganglion-cell photoreceptors: cellular diversity and role in pattern vision

Neuron

(2010)

M. Hatori et al.

Inducible ablation of melanopsin-expressing retinal ganglion cells reveals their central role in non-image forming visual responses

PLoS ONE

(2008)

D. Goz et al.

Targeted destruction of photosensitive retinal ganglion cells with a saporin conjugate alters the effects of light on mouse circadian rhythms

PLoS ONE

(2008)

S.K. Chen et al.

Photoentrainment and pupillary light reflex are mediated by distinct populations of ipRGCs

Nature

(2011)

T.A. LeGates et al.

Aberrant light directly impairs mood and learning through melanopsin-expressing neurons

Nature

(2012)

R. Noseda et al.

A neural mechanism for exacerbation of headache by light

Nat Neurosci

(2010)

J. Johnson et al.

Melanopsin-dependent light avoidance in neonatal mice

Proc Natl Acad Sci U S A

(2010)

S. Rao et al.

A direct and melanopsin-dependent fetal light response regulates mouse eye development

Nature

(2013)

L.A. Kirkby et al.

Intrinsically photosensitive ganglion cells contribute to plasticity in retinal wave circuits

Proc Natl Acad Sci U S A

(2013)

J.M. Renna et al.

Light acts through melanopsin to alter retinal waves and segregation of retinogeniculate afferents

Nat Neurosci

(2011)

T.M. Brown et al.

Melanopsin contributions to irradiance coding in the thalamo-cortical visual system

PLoS Biol

(2010)

Cited by (138)

The pulvinar as a hub of visual processing and cortical integration
2024, Trends in Neurosciences
The pulvinar nucleus of the thalamus is a crucial component of the visual system and plays significant roles in sensory processing and cognitive integration. The pulvinar’s extensive connectivity with cortical regions allows for bidirectional communication, contributing to the integration of sensory information across the visual hierarchy. Recent findings underscore the pulvinar’s involvement in attentional modulation, feature binding, and predictive coding. In this review, we highlight recent advances in clarifying the pulvinar’s circuitry and function. We discuss the contributions of the pulvinar to signal modulation across the global cortical network and place these findings within theoretical frameworks of cortical processing, particularly the global neuronal workspace (GNW) theory and predictive coding.
Neuroprotection in glaucoma: Mechanisms beyond intraocular pressure lowering
2023, Molecular Aspects of Medicine
Glaucoma is a common, complex, multifactorial neurodegenerative disease characterized by progressive dysfunction and then loss of retinal ganglion cells, the output neurons of the retina. Glaucoma is the most common cause of irreversible blindness and affects ∼80 million people worldwide with many more undiagnosed. The major risk factors for glaucoma are genetics, age, and elevated intraocular pressure. Current strategies only target intraocular pressure management and do not directly target the neurodegenerative processes occurring at the level of the retinal ganglion cell. Despite strategies to manage intraocular pressure, as many as 40% of glaucoma patients progress to blindness in at least one eye during their lifetime. As such, neuroprotective strategies that target the retinal ganglion cell and these neurodegenerative processes directly are of great therapeutic need. This review will cover the recent advances from basic biology to on-going clinical trials for neuroprotection in glaucoma covering degenerative mechanisms, metabolism, insulin signaling, mTOR, axon transport, apoptosis, autophagy, and neuroinflammation. With an increased understanding of both the basic and clinical mechanisms of the disease, we are closer than ever to a neuroprotective strategy for glaucoma.
Mapping visual functions onto molecular cell types in the mouse superior colliculus
2023, Neuron
The superficial superior colliculus (sSC) carries out diverse roles in visual processing and behaviors, but how these functions are delegated among collicular neurons remains unclear. Here, using single-cell transcriptomics, we identified 28 neuron subtypes and subtype-enriched marker genes from tens of thousands of adult mouse sSC neurons. We then asked whether the sSC’s molecular subtypes are tuned to different visual stimuli. Specifically, we imaged calcium dynamics in single sSC neurons in vivo during visual stimulation and then mapped marker gene transcripts onto the same neurons ex vivo. Our results identify a molecular subtype of inhibitory neuron accounting for ∼50% of the sSC’s direction-selective cells, suggesting a genetic logic for the functional organization of the sSC. In addition, our studies provide a comprehensive molecular atlas of sSC neuron subtypes and a multimodal mapping method that will facilitate investigation of their respective functions, connectivity, and development.
Activity-dependent Organization of Topographic Neural Circuits
2023, Neuroscience
Sensory information in the brain is organized into spatial representations, including retinotopic, somatotopic, and tonotopic maps, as well as ocular dominance columns. The spatial representation of sensory inputs is thought to be a fundamental organizational principle that is important for information processing. Topographic maps are plastic throughout an animal’s life, reflecting changes in development and aging of brain circuitry, changes in the periphery and sensory input, and changes in circuitry, for instance in response to experience and learning. Here, we review mechanisms underlying the role of activity in the development, stability and plasticity of topographic maps, focusing on recent work suggesting that the spatial information in the visual field, and the resulting spatiotemporal patterns of activity, provide instructive cues that organize visual projections.
A Guide for the Multiplexed: The Development of Visual Feature Maps in the Brain
2023, Neuroscience
Neural maps are found ubiquitously in the brain, where they encode a wide range of behaviourally relevant features into neural space. Developmental studies have shown that animals devote a great deal of resources to establish consistently patterned organization in neural circuits throughout the nervous system, but what purposes maps serve beneath their often intricate appearance and composition is a topic of active debate and exploration. In this article, we review the general mechanisms of map formation, with a focus on the visual system, and then survey notable organizational properties of neural maps: the multiplexing of feature representations through a nested architecture, the interspersing of fine-scale heterogeneity within a globally smooth organization, and the complex integration at the microcircuit level that enables a high dimensionality of information encoding. Finally, we discuss the roles of maps in cortical functions, including input segregation, feature extraction and routing of circuit outputs for higher order processing, as well as the evolutionary basis for the properties we observe in neural maps.
Pigment epithelium-derived factor and its role in microvascular-related diseases
2022, Biochimie
Microvascular diseases are among the most clinically important diseases, and vascular abnormalities are central in the development of such diseases. Pigment epithelium-derived factor (PEDF), a potent inhibitor of angiogenesis, exerts antiangiogenic effects without affecting the structure and function of normal blood vessels. PEDF also has neurotrophic effects, which may be a potential direction for the future treatment of angiogenic diseases with lower side effects. Here, we review (i) the expression levels of PEDF in several important organs and clinically common microvascular diseases and (ii) the effects of its absence and presence on the vasculature and nerves, focusing on both angiogenic and neuroprotective aspects. These effects are both positive and negative, and have the potential to be exploited. Additionally, we summarize and compare various PEDF agents and their possible advantages and disadvantages as therapeutic agents, which, despite most still being in the experimental stage, may provide some new opportunities for future clinical treatments and interventions in PEDF-targeted microvascular diseases.

View all citing articles on Scopus

View full text