Science - USA (2021-10-29)

SCIENCE science.org 29 OCTOBER 2021 • VOL 374 ISSUE 6567 548-B

PHOTO: FLUSSREIF

NEUROSCIENCE

Hidden in plain sight

Context controls the activity of sensory neurons

By Andreas J. Keller

W

here is Waldo? Despite his strik-

ing red-and-white–striped shirt,

Waldo (frequently known as Wally

outside the United States) of the

popular children’s puzzle-book

series “Where’s Waldo?” is consis-

tently difficult to find in the crowded illus-

trations in which he is embedded. Readers

must search a given scene meticulously to

find him and are often fooled by patterns

surrounding the elusive protagonist that re-

semble those of his shirt. Why is this seem-

ingly simple task so challenging for our vi-

sual systems?

Our perception of a visual stimulus is

strongly influenced by the scene surround-

ing the stimulus—the visual con-

text. Depending on its context,

the same visual stimulus may

be perceived as more or less sa-

lient, allowing it to stand out or

meld into the rest of the visual

scene. This contextual modula-

tion is what leads to a reduction

in our visual system’s response to

Waldo’s shirt. If he appeared alone, or was

at least the only one wearing a red-and-

white–striped shirt, he would be conspicu-

ous and spotted effortlessly.

SEEING THE STIMULUS AND THE SURROUND

Context gives meaning to sensations. Ac-

cordingly, sensory processing of a stimulus

is shaped by the context in which the stimu-

lus is embedded. My colleagues and I set

out to understand the neural circuits in the

mouse visual cortex responsible for contex-

tual modulation of sensory stimuli.

Every sensory neuron in the visual sys-

tem receives input from one region in space

and responds to stimuli placed in that re-

gion. Adjacent neurons in the visual cortex

receive input from surrounding regions in

space. The responses of excitatory neurons

are suppressed when stimulus and sur-

round are similar but are facilitated when

they differ. Somatostatin-expressing (SOM)

inhibitory neurons integrate information

from the surrounding regions and provide

surround suppression to other neurons ( 1 ).

Could these inhibitory neurons also account

for surround facilitation when stimulus and

surround differ?

Using optical recordings in the visual

cortex of awake mice, we found that SOM

neurons are active when stimulus and sur-

round are similar but not when they differ.

Conversely, inhibitory neurons expressing

vasoactive intestinal peptide (VIP)—the

main inhibitor of SOM neurons—are partic-

ularly active when stimulus and surround

differ ( 2 ).

COORDINATING CONTEXTUALIZATION

On the basis of these results and known

connectivity motifs between VIP, SOM, and

excitatory neurons ( 3 – 5 ), we hypothesized

a simple mechanism to explain contextual

modulation in excitatory neurons: When

stimulus and surround are similar,

SOM neurons are active and sup-

press excitatory neurons. When

stimuli and surround differ, VIP

inhibitory neurons are active, sup-

press SOM neurons, and thereby

relieve excitatory neurons from

suppression. Using computational

modeling, optical recordings, and

optogenetic perturbations, we showed that

VIP neurons orchestrate the amount of sup-

pression that SOM neurons provide to other

neurons ( 2 ). VIP neurons may coordinate

cortical circuits in adjusting the saliency of

a stimulus in a visual scene.

MAKING THE PICTURE WHOLE

Current dogma holds that neurons respond

to stimuli and are modulated by the visual

context. Context, however, can play more

than a supporting role. When a neuron’s vi-

sual information is missing—for example,

because of obstruction—its activity can

be driven by context alone ( 6 – 12 ), which

allows our sensory neurons to fill in the

gaps. Likely relying upon past visual ex-

perience, missing information is inferred

from the context.

The visual system comprises several

stages of processing. Information flows from

the retina to the primary visual cortex, from

where it is then sent to higher visual areas.

Information also flows in the opposite di-

rection through feedback projections from

higher visual areas to earlier stages of pro-

cessing. It is this reverse flow of information

that is responsible for filling the gaps when

visual information is missing ( 12 ).

Institute of Molecular and Clinical Ophthalmology Basel

(IOB), 4057 Basel, Switzerland. Email: [email protected]

FINALIST
Andreas J. Keller
Andreas Keller
received his un-
dergraduate and
graduate degrees in
physics from ETH
Zürich. His PhD work, completed
under Dr. Kevan Martin, focused on
rapid network state transitions in the
visual cortex. He joined the labora-
tory of Dr. Massimo Scanziani at
the University of San Francisco for
his postdoctoral training. Andreas
started his laboratory at the Institute
of Molecular and Clinical Ophthalmol-
ogy Basel in 2021, where his research
focuses on mechanisms of cortical
plasticity in feedforward and feed-
back circuits. science.org/doi/
10.1126/science.abl7124

PRIZE ESSAY

INSIGHTS