Please cite this article in press as: Reinagel P. Using rats for vision research. Neuroscience (2015), http://dx.doi.org/10.

1016/
j.neuroscience.2014.12.025

Neuroscience xxx (2015) xxxxxx

REVIEW
USING RATS FOR VISION RESEARCH
P. REINAGEL *

powerful methods are dicult or costly to perform in

animals with such large brains, however, including
lesions, slice physiology, recording or imaging
simultaneously from multiple visual areas, lling and
reconstructing individual cells, anatomic tracing of longrange projections, genetic labeling of specic cell types,
isolating mutants, transgenic animals, or comparisons
across large populations of individuals. Accordingly,
these methods are rarely employed in macaque vision
research, leaving gaps in our knowledge. Therefore a
small mammal with robust visual behavior would be
valuable for our research and for the eld in general.

Section of Neurobiology, Division of Biological Sciences, University

of California, San Diego, La Jolla, CA, United States

AbstractA wide variety of species are used for the study of

visual neuroscience. This is benecial because fundamental
mechanisms and theoretical principles of vision are likely to
be highly conserved, while dierent species exhibit dierent
visual capacities and present dierent technical advantages
for experiments. Eight years ago my laboratory adopted the
hooded rat as our primary preparation for vision research.
To some this may be surprising, as nocturnal rodents have
often been presumed to have poor vision and weak visual
behavior. This commentary will provide my personal perspective on how I came to work with rats; discuss an example research project for which rats have been advantageous;
and comment on the opportunities and challenges of the
preparation.
This article is part of a Special Issue entitled: Choice of
model
organisms
for
Neuroscience
Research.
2014 IBRO. Published by Elsevier Ltd. All rights reserved.

HOW WE CHOSE RATS

We considered a wide range of small mammal species,
and commenced pilot studies of visual behavior of
candidate species until a suitable preparation was
identied. In choosing candidates we considered visual
characteristics (prominence of visual system; percent of
photoreceptors
that
are
cones),
experimental
accessibility (suitability for optical imaging, slice
preparation, behavioral tractability), pragmatic factors
(size, availability, cost, maintenance burden, epizootic
problems, ease of handling), and research infrastructure
(existence of breeding colony, stereotaxic atlas, genome
sequence, genetic libraries), to the extent that these
facts were known. No species was ideal in all respects.
Balancing the advantages and disadvantages in
dierent ways, our top candidates were California
ground squirrel, degu, gerbil, guinea pig, rat, and
mouse. Our short list also included thirteen-lined ground
squirrel, Nile rat, hamster, tree shrew, ferret, and bush
baby. We began by testing four candidates. Two were
chosen for highly developed, cone-dominated visual
systems, in spite of limited research infrastructure:
California ground squirrel (Otospermophilus beecheyi)
and degu (Octodon degus). Two were chosen for highly
developed infrastructure, in spite of limited visual
systems: rat (Rattus norvegicus, specically the
pigmented Long-Evans strain), and mouse (Mus
musculus, specically the F1 hybrid of c57bl/6  dba/2).
The goal was to nd one small mammal that could
learn a visual task by operant conditioning with twoalternative forced choice (2AFC) trial design (rather than
gonogo), appetitive reward (as against negative
reinforcement, e.g., escaping water), liquid reward (as
against food pellets), and computer-displayed visual

Key words: rodent vision, visual behavior, pigmented rat,

visual psychophysics.
Contents
Introduction
How we chose rats
An example study using rats
Strengths and limitations of the rat preparation
Acknowledgements
References
Appendix A. Supplementary data

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INTRODUCTION
The development of the visually behaving macaque
model revolutionized visual neuroscience, allowing
neurophysiology to be directly linked with behavior on a
trial-by-trial basis. Immense progress has been made in
this preparation, and we expect it will remain the best or
only preparation for many visual studies. Several
*Address: Section of Neurobiology, Division of Biology, University of
California, San Diego, 9500 Gilman Drive #0357, La Jolla, CA 92093,
United States.
E-mail address: preinagel@ucsd.edu
Abbreviation: 2AFC, two-alternative forced choice.
http://dx.doi.org/10.1016/j.neuroscience.2014.12.025
0306-4522/ 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
1

P. Reinagel / Neuroscience xxx (2015) xxxxxx

stimuli (as against physical objects or cue cards). In these

respects, we mimicked conditions typical of human and
monkey visual behavior experiments, which are well
suited to providing a large number of trials in rapid
succession with temporal precision and minimal human
intervention.
Our pilot task was discrimination of high-contrast lowspatial frequency sinusoidal gratings at mesopic mean
luminance. We used an operant chamber that had been
previously developed for 2AFC olfactory and auditory
tasks in freely behaving rats (Uchida and Mainen, 2003;
Hromadka and Zador, 2007; Otazu et al., 2009). For control of visual stimuli, trials, and training we used an early
prototype of the training protocols and custom software
that were further developed and described in detail elsewhere (Meier et al., 2011, and supplementary materials
thereof). In the pilot study trials were initiated by insertion
of nose in the center nose poke, and terminated by
response at either the left or right nose poke. Correct
responses earned liquid reward; incorrect responses
earned a brief penalty time-out during which a ickering
checkerboard was displayed (see Supplemental Videos
1 and 2).
The rst species we succeeded in training were LongEvans hooded rats (Fig. 1A, B; Supplementary Video 1)
and California Ground Squirrels (Fig. 1C, D;
Supplementary Video 2). The rats we tested were
young adults (P30P90). The squirrels we tested were
captive-raised 1-year-old adults, born of wild-caught
pregnant mothers. The epizootic risks necessitated BL2
handling, o-site housing, and daily transportation by
car to the testing laboratory. Despite these sub-optimal
conditions the squirrels learned rapidly and performed
well in the task. In our initial pilot, neither mice nor
degus learned the visual task. We chose to proceed

with rats rather than squirrels because rats were able to

learn and perform all the visual tasks we needed, and
the existing research infrastructure for rats is far better
than for squirrels. With further eort, protocols have
since been optimized for freely behaving mice as well
(for preliminary report, see Sriram et al., 2013). We abandoned eorts to optimize protocols for degus, and did not
test the other candidate species, so their visual and
behavioral capacities in our task remain unknown.
Using rats as our primary preparation, we developed
software, hardware, and operant chambers for
automated training and testing of rodents in visual tasks
(Meier et al., 2011). The ability to train a large number
of subjects in a compact space is one signicant advantage of using a small mammal model. We note that other
groups had previously (Birch and Jacobs, 1979; Cowey
and Franzini, 1979; Keller et al., 2000; Prusky et al.,
2000) or contemporaneously (Douglas et al., 2006;
Minini and Jeery, 2006; Bussey et al., 2008; Zoccolan
et al., 2009) developed related methods for training and
testing vision in rodents, and new methods are emerging
daily, especially for mice (e.g., Chen et al., 2008; Harvey
et al., 2009; Andermann et al., 2010; Dombeck et al.,
2010; Niell and Stryker, 2010; Busse et al., 2011;
Harvey et al., 2012; Histed et al., 2012).

AN EXAMPLE STUDY USING RATS

We nd rats to be excellent subjects for studies that
require complex visual behaviors and large numbers of
trials from multiple subjects. To illustrate this, consider
our use of rats to study spatial context eects (Meier
et al., 2011; Meier and Reinagel 2011; Meier and
Reinagel 2013). A question of broad interest in vision
research is to understand how spatially proximal visual

Fig. 1. Small animals tested for visual behavior. (A) Long-Evans hooded rat in pilot test, performing 2AFC orientation discrimination. (B)
Performance of one of the rats as a function of spatial frequency (8437 trials over 18 days). (C) California Ground Squirrel in pilot test, performing
2AFC orientation discrimination. (D) Performance of one of the squirrels as a function of spatial frequency (797 trials over 2 days). Mice and
Octodon degus were also tested, but performed poorly under the pilot test conditions.
Please cite this article in press as: Reinagel P. Using rats for vision research. Neuroscience (2015), http://dx.doi.org/10.1016/
j.neuroscience.2014.12.025

P. Reinagel / Neuroscience xxx (2015) xxxxxx

information alters the primary perception of local visual

cues. At a basic level, the eective contrast of local visual
stimuli is normalized by surrounding contrast, a computation that arises as early as the retina. We were specically
interested in contextual interactions that are sensitive to
higher organizing principles, such as the collinearity of
an oriented stimulus with its surrounding context. It is
plausible that specic lateral interactions in primary visual
cortex might underlie such conguration-dependent perceptual eects. This hypothesis has been dicult to test,
however, as the behavioral evidence has been mainly
from humans. Therefore our goal was to establish a small
animal model for conguration-sensitive contextual
eects on visual perception.
The task we adopted is a anker detection task. The
subject must report the presence or absence of a small
oriented grating patch (target) in the center of the
display, while ignoring oriented grating patches at other
nearby locations anking the target (Fig. 2A). In
humans, detection is aected by anking stimuli in
general, and by collinear ankers in particular (Ejima
and Takahashi, 1985; Polat and Sagi, 1993, 2007; Xing
and Heeger, 2001; Chen and Tyler, 2008; Chubb et al.,
1989; Zenger and Sagi, 1996; Cannon and Fullenkamp,
1996; Williams and Hess, 1998; Solomon and Morgan,
2000). Flanker tasks have also been explored in nonhuman primates (Li et al., 2006; Pooresmaeili et al.,
2010).
There were many challenges and unknowns in
adapting this task to rats. It was unclear whether rats
would be able to learn such a task, which demands a
kind of spatially selective attention. Moreover, the
eects of context can be small, sometimes just a few
percent change in performance. To resolve such subtle
eects, rats would need to perform a large number of
trials with stable performance. Even if eects such as
contrast normalization could be demonstrated in rats,
rodents lack orientation-column architecture in V1,
which might have been essential for congurationspecic lateral interactions. We found, however, that
rats could perform the task, contextual eects exist and
could be resolved, and the eect of ankers was
sensitive to collinear conguration (Fig. 2B, C; Meier
et al., 2011).
The advantage of using rats for this study was the
ability to train several (N = 7) subjects in parallel on a
dicult visual task and collect very large numbers of
trials in a modest time frame. On average, na ve rats
reached stable performance on the anker detection
task in a total of 26,000 trials over 103 days. The rats
then had stable performance for months, allowing us to
collect on average 55,000 trials of behavioral data per
rat over a period of 25 months (98 63 days).
This large trial number provided the statistical power
to fully explore relevant stimulus parameters and control
conditions, and to resolve even small dierences in
performance across conditions. Because all seven
subjects were trained in parallel, the entire training and
data collection period was about six months. Rats have
a natural lifespan of at least two years in the laboratory,
allowing highly trained subjects to be used for multiple

Fig. 2. Rats tested in a anker detection task. (A) Rat performing the
task, which was to report the presence or absence of a central grating
patch while ignoring the anking patches. (B) Average performance
(% correct) of rats as a function of anker conguration. When
ankers were collinear (red), detection was selectively impaired
(N = 7 rats). (C) Dierence in performance between the collinear
condition and a conguration with non-collinear ankers at the same
locations. For six individual rats (blue), performance was signicantly
lower when ankers were collinear. For one rat the dierence was not
signicant (gray). (Image and gures reproduced from Meier et al.,
2011).

experiments. In this study, for example, two rats were

tested for another three months while we varied a
dierent set of stimulus parameters, allowing us to build
a detailed quantitative model that was highly
constrained by empirical measurements (Meier and
Reinagel, 2011). We are not aware of any other animal
model in which one could produce such a large behavioral
dataset in an equivalent time frame and budget.
There are two signicant caveats to this story. First,
we have only behavioral data so far, which could also
have been collected from human subjects. The power of
having an animal model is yet to be exploited. But in
principle, manipulation of the visual circuits during
behavior is now feasible. Moreover, our quantitative
models can be usefully combined with independently
collected data on the biophysics, cellular physiology,
micro circuitry, and visual electrophysiology of rat
primary visual cortex. The second caveat is that the
psychophysical eects we nd in rats are not the same
as found in humans (Meier and Reinagel, 2013). Therefore the rat is not an exact model for the visual processing
and sensory decision-making of humans. What the rat
does provide is a viable model of how conguration-sensitive spatial context eects, including collinearity computation, can arise in a mammalian visual cortex.

STRENGTHS AND LIMITATIONS OF THE RAT

PREPARATION
Based on our work and work in other labs, we now know
that rats can rapidly learn and reliably perform many
complex visual tasks, such as visual object
discrimination (Zoccolan et al., 2009; Clark et al., 2011;
Tafazoli et al., 2012; Vermaercke and Op de Beeck,

Please cite this article in press as: Reinagel P. Using rats for vision research. Neuroscience (2015), http://dx.doi.org/10.1016/
j.neuroscience.2014.12.025

P. Reinagel / Neuroscience xxx (2015) xxxxxx

2012; Alemi-Neissi et al., 2013; Petruno et al., 2013;

Brooks et al., 2013), random dot motion discrimination
(Douglas et al., 2006; Petruno et al. 2013; Reinagel,
2013), and detection with anking distractors (Meier
et al., 2011; Meier and Reinagel, 2011). The anker
detection is the most dicult task we have trained rats
to perform, as judged by the unusually long training time
(100 days). Other visual tasks can be acquired much
more quickly. For example, if only detection is required,
rats can learn to report the side on which a stimulus
appears in just a few days, and to perform 2-AFC visual
discrimination in about a week (Clark et al., 2011;
Petruno et al., 2013; Reinagel 2013).
In addition to visual psychophysics, we also nd the
rat preparation valuable for studies requiring complex
visual behavior in combination with lesions. For
example, rats can perform subtle visual object
discriminations, which enabled a test of the role of the
perirhinal cortex in this visual computation (Clark et al.,
2011). Individual rats can be trained to perform a battery
of disparate tasks (stimulus localization, orientation discrimination, random-dot motion discrimination, and photographic image discrimination); this has enabled a test of
the perceptual function of V1 and medial extra-striate cortex (Petruno et al., 2013). Primates could easily perform
the same behaviors, but lesion studies in primates are
costly and necessarily limited in number. Although mice
are amenable to lesions, we have so far found them more
dicult to train.
An important motivation for using rats is that we are
developing behavioral paradigms and computational
theories in a preparation that will also be accessible to
tools of circuit analysis and manipulation going forward.
Compared with the behaving macaque monkey, we
expect that visually behaving rats will be a preferred
preparation for methods such as slice physiology, viral
vector gene expression, cell lling, and anatomic
projection tracing.
It remains to be determined whether rats can perform
all the complex visual tasks now established in the
macaque preparation, however. Rats have very few
cones, lack color vision, and have a very limited
binocular eld (although California Ground Squirrels are
comparable to macaques in these respects). For studies
requiring sophisticated genetics, the mouse will be the
preparation of choice, although it remains to be
determined whether mice can learn and perform all the
tasks that are now established in rats. In summary, we
nd the rat to be a valuable preparation for vision
research that is complementary to other established and
emerging models.
AcknowledgementsThe opinions expressed here are my own.
Without implication of endorsement, I wish to acknowledge my
debt to Harvey Karten for valuable discussion in the identication
of candidate species, and to Tony Zador and Zach Mainen for
helping us replicate and adapt their rat behavioral apparatus.
The behavioral pilot experiments were carried out in my laboratory by Erik Flister, Philip Meier, Bevil Conway, and Elizabeth
Murphy, with expert technical support from Pamela SchupMagon. The multi-species pilot study was supported by the
Hellman Fellows Fund.

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APPENDIX A. SUPPLEMENTARY DATA

Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/
j.neuroscience.2014.12.025.

(Accepted 13 December 2014)

(Available online xxxx)