The Scientist November 2018

11.2018 | THE SCIENTIST 27

MODUS OPERANDI

© GEORGE RETSECK

AT A GLANCE

T

he eye presents a paradox to experimental neuroscientists. On one

hand, it’s accessible, its function is well understood, and its inputs

can be precisely controlled, says neurobiologist William Newsome

of Stanford University. “On the other hand, it is very diffi cult to record

its electrical signals while visual behavior is actually taking place.” That’s

because the hardware for electrical recordings—rigid electrodes—aren’t

compatible with small, spherical, constantly moving rodent eyes.

To record retinal cell activity, researchers tend to remove the eye from

the animal, dissect the retina, and lay it fl at on an array of microelectrodes.

While such preparations can continue to respond to light for a matter

of hours, new mesh electrodes, developed by nanotechnologist Charles

Lieber of Harvard University and colleagues, can remain inside a living ani-

mal’s eye, recording the same cells for several weeks.

Measuring 1.5 mm by 0.8 mm and containing 16 individual elec-

trodes, the polymer and metal meshes are injected, one per mouse eye,

toward the rear of the vitreous body, where they unfurl to coat the retina.

Tiny wires connected to the meshes extend out of the corner of the ani-

mals’ eyes for attachment to an external recording device. The animals are

restrained, their heads immobilized, for sessions of light stimulation and

recording, but they are free to move and behave normally between ses-

sions. Remarkably, the meshes have little eff ect on vision, and after a few

weeks they detach from the retina.

Long-term, in vivo recording ability opens a range of new research

avenues, says Lieber, whose team has used the meshes to measure

changes in retinal ganglion cell activity over the course of several day/

night cycles.

It’s a “fantastic” innovation, says Marla Feller of the University of Cal-

ifornia, Berkeley, who studies the organization of retinal neural circuits

during development but was not involved in the research. “It was exciting

to see how successful it was at being able to record from the same cells

over multiple days.” Not only might the method be useful for following

individual cells through retinal maturation, she says, but also for examining

which cells die and which survive during eye diseases such as glaucoma.

(Science, 360:1447–51, 2018) g

Ultrafl exible mesh electrodes monitor intact, functioning eyes

of awake animals.

BY RUTH WILLIAMS

Retina Recordings Reinvented

MULTI-CELL RETINAL

RECORDINGS

Ex vivo

In vivo

METHOD

The eye is removed, and the

retina is dissected and laid fl at

on an array of microelectrodes.

Mesh electrode is injected into the

eye of an anesthetized mouse.

VIABLE

RECORDING TIME

8 to 12 hours for mouse

retinas

Several weeks

NO. OF SIMULTANEOUSLY

RECORDING ELECTRODES

Approximately 500

16 so far but could

theoretically be more

INVASIVE?

Highly. Animal

sacrifi ced

Minimally.

Visual function

negligibly

aff ected

Tiny wires connected to the meshes extend out of the corner of the ani- (Science, 360:1447–51, 2018) g

AT A GLANCE

 1 ^2

Light

stimulation

ENVISIONED:  1 A mesh of multiple electrodes is injected toward the rear of the mouse eye, where it unfurls onto

the retina.  2 Wires connected to the mesh extend from the corner of the animal’s eye to enable electrical recording

of retinal activity in response to stimulation, such as bars of light shown on a screen.