European Journal of Neuroscience, pp. 1–12, 2018 doi:10.1111/ejn.

13830

Adaptation to stimulus orientation in mouse primary visual

cortex

Jillian L. King and Nathan A. Crowder

Department of Psychology and Neuroscience, Dalhousie University, 1355 Oxford Street, PO Box 15000, Halifax, NS, B3H 4R2,
Canada

Keywords: animal model, comparative neuroscience, electrophysiology, tilt-after-effect, vision

Abstract
Information processing in the visual system is shaped by recent stimulus history, such that prolonged viewing of an adapting stim-
ulus can alter the perception of subsequently presented test stimuli. In the tilt-after-effect, the perceived orientation of a grating is
often repelled away from the orientation of a previously viewed adapting grating. A possible neural correlate for the tilt-after-effect
has been described in cat and macaque primary visual cortex (V1), where adaptation produces repulsive shifts in the orientation
tuning curves of V1 neurons. We investigated adaptation to stimulus orientation in mouse V1 to determine whether known species
differences in orientation processing, notably V1 functional architecture and proportion of tightly tuned cells, are important for
these repulsive shifts. Unlike the consistent repulsion reported in other species, we found that repulsion was only about twice as
common as attraction in our mouse data. Furthermore, adapted responses were attenuated across all orientations. A simple
model that captured key physiological findings reported in cats and mice indicated that the greater proportion of broadly tuned
neurons in mice may explain the observed species differences in adaptation.

Introduction
Studies of sensory adaptation and/or after effects suggest that the
visual system possesses a number of mechanisms to calibrate itself
based on what has been viewed in the recent past (for reviews see
Carandini, 2000; Kohn, 2007). Adaptation to the orientation of an
edge or texture is especially interesting because unlike brightness,
colour or contrast, this process is thought to emphasize the primary
visual cortex (V1) and extrastriate areas as antecedent stages of anal-
ysis show little selectivity for orientation (but see Smith et al.,
1990; Xu et al., 2002; Kuhkmann & Vidyasagar, 2011; Naito et al.,
2013). In the tilt-after-effect and similar visual illusions, prolonged
viewing of an adaptor grating causes the orientation of the subse-
quently presented test grating to appear shifted away from (or ‘re-
pelled’ by) the adaptor’s orientation (Gibson & Radner, 1937;
Levinson & Sekuler, 1976; Patterson & Becker, 1996; Schrater &
Simoncelli, 1998; Clifford, 2002). A potential neural correlate for
these perceptual effects has been described in cat and macaque,
where adaptation within the classical receptive field of V1 neurons
produces repulsive shifts in the orientation tuning curves of these
cells (Dragoi & Sur, 2000; Dragoi et al., 2001; Wissig & Kohn,
Correspondence: Nathan A. Crowder, as above. E-mail: nathan.crowder@dal.ca
Received 25 August 2017, revised 15 December 2017, accepted 8 January 2018
Edited by Panayiota Poirazi. Reviewed by Athanassia Papoutsi, Institute of Molecular
Biology and Biotechnology, Greece; and Nicholas Price, Monash University, Australia
All peer review communications can be found with the online version of the article.
2012; Patterson et al., 2013). Several related studies have made pro-
gress in establishing how aspects of the stimulus protocol can affect
the nature of orientation adaptation (duration of adaptation: Dragoi
& Sur, 2000; Ghisovan et al., 2009; adapting angle: Patterson et al.,
2013; and stimulus size: Wissig & Kohn, 2012), but there are many
remaining details to be revealed about the neural mechanisms under-
lying this form of short-term plasticity.
We examined orientation adaptation in the mouse primary visual
cortex to gain a comparative perspective on this phenomenon. Despite
mice having spatial acuity up to two orders of magnitude lower than
classical animal models of vision (Wong & Brown, 2006), mouse V1
neurons share many features with those of more visual species includ-
ing: tuning for spatial and temporal frequencies (Gao et al., 2010); the
presence of simple and complex cells (Liu et al., 2009; Van den
Bergh et al., 2010); binocular disparity selectivity (Scholl et al.,
2013); and most relevant for the current work, selectivity for orienta-
tion and direction (Niell & Stryker, 2008; Liu et al., 2011; Tan et al.,
2011). Critically, however, there are also at least three differences in
the way orientation information is dealt with in mouse V1 compared
to classical models. First, there is a larger proportion of neurons that
are not selective or poorly tuned for orientation in mouse V1 (Niell &
Stryker, 2008; Gao et al., 2010; Liu et al., 2011; Tan et al., 2011;
Stroud et al., 2012). Second, there is evidence that orientation selec-
tivity emerges prior to V1 in the mouse, and the sharpening of orienta-
tion tuning as signals pass from the dorsal lateral geniculate nucleus
(dLGN) to V1 is not as dramatic as in cats or primates (Li et al.,
2013; Piscopo et al., 2013; Scholl et al., 2013; Zhao et al., 2013; but

© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
2 J. L. King and N. A. Crowder
see Lien & Scanziani, 2013). Finally, whereas cats and primates have
columns of orientation selective V1 neurons organized into an orienta-
tion map with iso-orientation domains that converge in pinwheel cen-
tres, these orientation maps are either absent or poorly developed in
mice (Ohki et al., 2005; Ringach et al., 2016). This last difference
may be especially important because there is evidence that orientation
adaptation in cats depends on neuronal location within the orientation
map (Dragoi et al., 2001). Any differences in the pattern of orienta-
tion adaptation between species could indicate that the features absent
from the mouse are the ones which are critical for the repulsive shifts
seen in the traditional animal models.
We investigated the effects of adaptation on the orientation tuning
of mouse V1 neurons using single unit recording and adaptation
paradigms that were comparable with previous studies in cat and
monkey (Dragoi et al., 2001; Wissig & Kohn, 2012; Patterson et al.,
2013). We found that unlike in other species, adaptation induced
repulsive shifts in the tuning curves of orientation selective neurons
only about twice as frequently as it induced attractive shifts. We also
found that adaptation attenuated responses across all orientations, and
this effect appears to be more pronounced in mice than in other spe-
cies. We used a simplified model to show that these differences in
adaptation found in mice could arise from the greater proportion of
neurons that are broadly tuned or poorly modulated by orientation in
this species.
Materials and methods
Animals
Extracellular recordings were performed on 27 male C57BL/6J mice
obtained from The Jackson Laboratories (JAX stock # 000664) 2–
7 months of age and weighing 22–33 g. All experimental proce-
dures were performed in accordance with the guidelines of the
Canadian Council on Animal Care and were approved by the Dal-
housie University Committee on Laboratory Animals.
Physiological preparation
Animals were pre-medicated with an injection of chlorprothixene
(5 mg/kg I.P.; Sigma Aldrich) and then placed in a custom face
mask and anaesthetized with isoflurane in oxygen for the remainder
of the experiment (2.5% isoflurane during induction, 1.5% during
surgery and 0.5% during recording; Pharmaceutical Partners of
Canada). Additional doses of chlorprothixene were given every four
hours. Once anesthetized, mice were maintained at a body tempera-
ture of 37.5 °C with a heating pad, and their corneas were protected
by frequent application of optically neutral silicone oil (30 000 cSt,
Sigma-Aldrich). In preparation for electrophysiological recordings,
the scalp was removed and a head post was secured using dental
epoxy. A small craniotomy (~1 mm2) was then made 0.8 mm ante-
rior and 2.3 mm lateral from lambda (Paxinos & Franklin, 2001). A
wall of petroleum jelly surrounded the craniotomy and was filled
with saline to prevent dehydration of the cortex. The pupils were
not dilated so as to maintain a large depth of focus, and the eyes
were not immobilized because eye movements under anaesthesia
have been shown to be negligible in mice (Wang & Burkhalter,
2007; Niell & Stryker, 2008; Gao et al., 2010).
Extracellular recordings were made with glass micropipettes con-
taining 2 M NaCl, with a tip diameter of 2–5 lm. Signals from indi-
vidual units were isolated, amplified, filtered, and acquired with a
CED 1401 interface and Spike2 software (Cambridge Electronic
Designs, Cambridge, UK) sampled at 40 kHz. Online responses were
© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
generated in Spike2 from triggered transistor-transistor logic (TTL)
pulses from a window discriminator (Cornerstone by Dagan). Spike
sorting was performed offline with Spike2 software, which first
searched for and sorted spikes using a supervised template-matching
algorithm, and then displayed candidate spikes. We used a principle
components analysis to check the clustering of spike waveforms. Data
were exported to MATLAB (Math Works, Natick, MA, USA) and neu-
ronal responses were represented as spike density functions with
1 kHz resolution, generated by convolving a delta function at each
spike arrival time with a Gaussian window.
Visual stimuli
Once a visually responsive neuron was isolated, the receptive field
(RF) was mapped by hand using an ophthalmoscope. Quantitative
stimuli, which were programmed in MATLAB using the Psychophysics
Toolbox extension (Brainard, 1997; Pelli, 1997), were presented on a
calibrated CRT monitor (LG Flatron 915FT Plus 19 inch display,
100 Hz refresh, 1024 9 768 pixels, mean luminance = 30 cd/m2) at
a viewing distance of 20–30 cm. All stimuli were presented for 8–12
repetitions. Each unit’s preferred orientation, RF size, spatial fre-
quency (SF), and temporal frequency (TF) were analyzed online to
ensure robust responses during the orientation adaptation protocol.
Preferred size was tested with two stimuli: (1) sine-wave gratings in
different sized circular apertures, and (2) a full field grating with dif-
ferent sized grey discs at its centre. These two stimuli helped centre
the monitor, and ensured the stimulus was placed within the neuron’s
classical receptive field. The size of the circular aperture used for all
subsequent stimuli was chosen as either the diameter where the size
tuning function began to asymptote in neurons lacking surround sup-
pression or the peak of the size tuning function for neurons that
showed surround suppression.
Orientation adaptation
For the orientation adaptation protocol, orientation tuning was measured
with drifting square-wave gratings (SF = 0.03 cpd; TF = 2 Hz; con-
trast = 1) spaced 18° apart and spanning 180° centred on the unit’s pre-
ferred orientation as determined from the online analysis. Drifting test
gratings with randomly selected orientations were presented for 2 s each.
On adapted trials, this test grating was preceded by a 2-s drifting adaptor
grating, whereas on nonadapted trials this test grating was preceded only
by a grey of mean luminance (Fig. 1A). We attempted to select an
adapting orientation that fell midway between the peak and trough of the
orientation tuning curve (flank adaptation), but there was enough vari-
ability that some units were adapted near their peak, whereas other adap-
tors were nearly orthogonal to the peak. We referred to adaptation with a
stimulus that elicited firing ≤ 10% above the untuned baseline of the
control orientation tuning curve as end-of-flank adaptation (Kohn &
Movshon, 2004). Adapted and nonadapted trials were randomized, and
a grey of mean luminance was shown for the 6-s interstimulus interval
(ISI) between trials. This ISI was based on pilot data from 10 neurons
where we measured recovery from adaptation by comparing spike rates
elicited by adapting gratings that followed either nonadapted or adapted
trials and found no evidence of a difference between these conditions for
the 6-s ISI (P = 0.35, paired t-test).
Data analysis
The least squares method was used to fit each orientation tuning
curve to a von Mises function, which is a circular Gaussian often
used in modelling orientation selectivity (e.g. Swindale, 1998):
European Journal of Neuroscience, 1–12

Fig. 1. Adaptation to orientation in mouse V1 neurons. (A) Diagram depict-
ing the timing of the orientation adaptation protocol, with adapting stimuli
(white blocks), test stimuli (black blocks), and inter-stimulus intervals (grey
blocks) aligned with spiking activity of a sample neuron. (B–E) Orientation
tuning curves of four sample neurons with orientation on the abscissa and
mean response rate on the ordinate. Control and adapted conditions are
shown as filled and empty circles, respectively. Thin curves represent best
fits of a von Mises function to the control (solid) or adapted (dashed) data.
The spike trace in A and tuning curves in B are from the same unit. Solid
vertical lines indicate the adapting orientation, and dashed horizontal lines
indicate the spontaneous activity. All error bars indicate SEM.
rp ðhÞ ¼ m þ aebðcosðhhpref Þ1Þ ð1Þ
where the response (rp) at a given angle (h) is determined by the tun-
ing bandwidth (b), preferred orientation (hpref), amplitude (a) and
baseline response rate (m). Goodness of fits were calculated with R2.
Two simpler functions were also fit to the data to further characterize
tuning curve shapes: (1) data points from the control condition were
fit to a straight line (2 free parameters) to obtain a statistical measure
of orientation selectivity; and (2) data points from the adapted condi-
tion were fit to a modified von Mises function with hpref fixed at the
nonadapted value (3 free parameters) to obtain a statistical measure
for peak shift. An F-test was then used to compare the fits of the four
parameter von Mises function to these simpler functions:
ðSS1  SS2 Þ=ðdf 1  df 2 Þ
F¼ ð2Þ
ðSS2 Þ=ðdf 2 Þ
where SS1 is the residual sum of squares for the simpler function, and
SS2 is the residual sum of squares for von Mises function. The degrees
© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
European Journal of Neuroscience, 1–12
Orientation adaptation in mouse V1 3
of freedom for the simpler function (df1) and von Mises functions (df2)
were calculated as the number of data points minus the number of free
parameters being estimated. A P-value was then calculated to determine
whether the von Mises curve fits the data significantly better than the
simpler function using the MATLAB ‘fcdf’ function.
Each unit’s selectivity for stimulus orientation was also quantified
using a discrimination index for orientation (DIo), which accounts
for both depth of tuning and the variability of responses (Gao et al.,
2010):
RespMax  RespMin
DIo ¼ pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffi ð3Þ
RespMax  RespMin þ 2 SSE=ðN  M Þ
where RespMax and RespMin are the maximum and minimum
responses of the neuron to drifting gratings, SSE is the sum of squares
error, N is the total number of stimuli presented (orientations 9
repetitions), and M is the number of different orientations.
The final analysis quantified how many spatially phase sensitive
units were in our sample using the F1/F0 ratio. The F1/F0 ratio is
determined by dividing the first Fourier coefficient of the response
(F1) by the mean time-averaged response (F0). This F1/F0 ratio has
been used in classical animal models of vision to categorize orienta-
tion tuned V1 neurons as simple (F1/F0 > 1) or complex types (F1/
F0 < 1; e.g. Skottun et al., 1991). Here we use the nomenclature of
phase sensitive (F1/F0 > 1) and phase invariant (F1/F0 < 1) because
not all of the units in our sample were orientation selective.
Statistical analysis
We used parametric analyses (specific tests noted in Results)
because the data of interest appeared to be approximately normally
distributed. The Benjamini-Hochberg procedure for controlling false
discovery rate was applied (33 total comparisons), and adjusted P-
values are reported (Benjamini & Hochberg, 1995).
Modelling
We implemented a simplified feed-forward model to explore poten-
tial mechanisms underlying species differences in orientation adapta-
tion. The model simulated the responses of individual extra-granular
V1 neurons by pooling signals from a population of orientation
tuned excitatory and inhibitory inputs and then generating firing
rates with a power-law nonlinearity (Priebe & Ferster, 2008; Tan
et al., 2011). We modelled two sources of adaptation: (1) each input
underwent firing rate-dependent divisive scaling; and (2) the simu-
lated neuron underwent activity-dependent hyperpolarization (Dhruv
et al., 2011; Wissig & Kohn, 2012). We used a population of 200
of these simulated neurons to capture the major features and spec-
trum of effects observed in our data.
We defined excitatory input (rexcite) to each simulated neuron as a
scaled population of von Mises curves:
" !#
X
n   euðcosðhhi Þ1Þ
hðcosðhi hnom Þ1Þ
rexcite ðhÞ ¼ c þ de 
i¼1 1 þ geuðcosðhadapt hi Þ1Þ
ð4Þ
where hi is the preferred orientation of input i, hadapt is the angle of
the adapting grating, u is the bandwidth of input i, and g is the gain
of divisive scaling from adaptation (which is set to 0 in the control
condition). The divisive scaling of each input is firing rate depen-
dent because part of the denominator (euðcosðhadapt hi Þ1Þ ) calculates
4 J. L. King and N. A. Crowder
the firing of input i at the adapting angle. Excitatory synaptic
strength among V1 neurons is highest between neurons with similar
tuning properties (Cossell et al., 2015), so we scaled the amplitude
of each von Mises curve based on tuning similarity to the simulated
neuron. Thus, hnom is the nominal preferred orientation of the simu-
lated neuron as dictated by the strength of its synaptic inputs, h is
the bandwidth of this synaptic selectivity, d determines the gain of
the synaptic selectivity scaling factor, and c is an offset that allows
some influence from inputs with dissimilar tuning. We used 50 exci-
tatory and inhibitory inputs (n), but similar results were observed
when n was 20–200. The preferred orientations (hi) for the popula-
tion of inputs were taken from a normally distributed n-long list of
random numbers. The standard deviation of this list was varied to
simulate members of the local cortical network available in cat ori-
entation tuning columns or mouse salt-and-pepper orientation tuning
(Dragoi et al., 2001; Ohki et al., 2005; Nauhaus et al., 2008).
For simplicity, inhibitory input (rinhibit) did not include a synaptic
strength scaling mechanism, but merely functioned as a broadly
tuned normalization pool (Carandini & Heeger, 2012):
! (hpref); adaptation-induced suppression was measured as changes in
X
n
epðcosðhhj Þ1Þ
rinhibit ðhÞ ¼
j¼0 1 þ qepðcosðhadapt hj Þ1Þ
where hj is the preferred orientation of input j, p is the bandwidth of
input j, and q is the gain of divisive scaling from adaptation (which
is set to 0 in the control condition). As with excitation, the preferred
orientations (hj) for the population of inhibitory inputs were taken
from a normally distributed n-long list of random numbers, but the
standard deviation of this distribution was always large to simulate a
broadly tuned divisive normalization pool. The total input to the cell
was defined as follows:
rexcite ðhÞ
rinput ðhÞ ¼
1 þ rinhibit ðhÞ
The spiking response of the model neuron was generated by
applying a power-law nonlinearity to the input:
rspike ðhÞ ¼ jrinput ðhÞ  Vthresh jwþ
where Vthresh is the spiking threshold, ||+ indicates half-wave rectifi-
cation, and w is the exponent (Priebe & Ferster, 2008; Tan et al.,
2011). Following Wissig & Kohn (2012), we implemented an activ-
ity-dependent hyperpolarization (simulated as an increase in thresh-
old) to serve as a second adaptation mechanism:
Vthresh adapted ¼ Vthresh þ rspike ðhadapt Þ½k1  k2 ðhnom  hadapt Þ
where k1 and k2 are arbitrary constants chosen to simulate the range of
effects in our data set. Deeply modulated orientation tuning curves
will show more hyperpolarization when the adapt angle is closer to
their preferred orientation, whereas poorly modulated tuning curves
will show similar amounts of hyperpolarization at all angles.
Results
We analysed the effects of adaptation on orientation tuning in 120
units recorded in mouse V1. Like Gao et al. (2010), our sample
contained more phase-invariant (107) than phase-sensitive units
(13), but adaptation affected these two groups similarly so they were
pooled in all subsequent analyses. Adaptation effects did not corre-
late with recording depth either, so we made no attempt to segregate
units by cortical layer.
The sample neurons in Fig. 1B–E demonstrate not only the spec-
trum of orientation tuning in our sample, but also the variability of
adaptation effects. The neurons in Fig. 1B and C both had well
tuned nonadapted orientation tuning functions (filled circles). The
adapted responses (empty circles) of the cell in Fig. 1B showed
repulsion from the adapting angle (vertical line), whereas the
adapted responses of the cell in Fig. 1C show a generalized
response reduction with little repulsion. The cell in Fig. 1D is an
example of end-of-flank adaptation in a cell with a robust untuned
component in its orientation function, which again produced a gen-
eralized response reduction with little repulsion. Figure 1E shows
the effect of adaptation in a poorly tuned neuron. The smooth curves
in Fig. 1B–E show von Mises fits to the nonadapted (solid lines)
and adapted (dotted lines) data. We used parameters from these fits
to quantify the effects of adaptation: repulsive or attractive peak
shifts were measured as the change in the preferred orientation
both peak height (a) and baseline (m); finally, changes in the
ð5Þ
breadth of orientation selectivity were measured using tuning band-
width (b) and half-width at half-maximum above the untuned base-
line (HWHM; following Niell & Stryker, 2008).
Segregation of orientation tuned cells
It is apparent from the sample neurons in Fig. 1 that some cells
were much more orientation selective than others. Therefore, reason-
ing that a neuron’s adaptation to a specific orientation is only mean-
ingful if it can reliably distinguish between different orientations, we
chose to segregate our data into orientation tuned and nonoriented
cells. Orientation selective units had: (a) an R2 ≥ 0.5 for the von
Mises curve fits to ensure the data were not too jagged; and (b) a
ð6Þ
DIo ≥ 0.425, which corresponded to approximately 2 : 1 modula-
tion. We also ensured that using more liberal (DIo ≥ 0.225) or con-
servative (DIo ≥ 0.625) cut-offs did not introduce any noticeable
biases to our main adaptation effects. Our sample contained 56 ori-
entation tuned and 64 nonoriented units, and this proportion fell
within previously reported ranges (Niell & Stryker, 2008; Gao et al.,
ð7Þ
2010). Furthermore, our median nonadapted HWHM for orientation
tuned cells was 29.7° (interquartile range = 19.6–48°), which is sim-
ilar to the median of 28° reported by Niell & Stryker (2008). The
median bandwidth was 4.92 (interquartile range = 1.7–11.4). All
units that passed our criteria for orientation selectivity had signifi-
cantly better fits to a von Mises function than a straight line
(P < 0.05; see Eqn 2 in Materials and methods), whereas no units
that failed our criteria had significantly better fits.
ð8Þ Before focusing exclusively on orientation tuned neurons, it is
important to note that nonoriented cells were strongly visually
responsive and consistently showed adaptation. When our discrimi-
nation index (Eqn 3 in Materials and methods) was modified to
measure how well neurons could distinguish between the preferred
grating stimulus and a uniform grey field that elicited spontaneous
activity, there was no evidence of a difference between nonoriented
and orientation tuned cells (P = 0.21, two-sample t-test). We used
the change in the baseline normalized to the nonadapted maximal
firing rate as a common measure of adaptation across all neurons (as
other parameters like tuning width or preferred orientation were
invalid for nonoriented cells) and found orientation tuned neurons
showed similar mean decreases in baseline (0.25) to nonoriented
© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
European Journal of Neuroscience, 1–12
 Orientation adaptation in mouse V1 5

cells (0.21) with no evidence of a population difference (P = 0.06,

two-sample t-test).

Population measures of adaptation

When examining adaptation effects across our population of orienta-
tion tuned cells, we first distinguished between flank adaptation
(n = 43) and end-of-flank adaptation (n = 13) because it has been
previously shown in primates that flank adaptation causes mainly
repulsion, whereas the effects of end-of-flank adaptation are more
variable (Wissig & Kohn, 2012; Patterson et al., 2013). We anal-
ysed changes in peak shift, peak height, baseline, bandwidth,
HWHM, and DIo with six mixed repeated-measures ANOVAs with
adaptation (within condition: control vs. adapted) and the flank
effect (between condition: flank vs. end-of-flank adaptation) as fac-
tors. For each ANOVA, we were interested in the main effect of adap-
tation, and the flank interaction that indicated whether there was a
different amount of adaptation in flank or end-of-flank conditions.
Adaptation produced ‘repulsive’ shifts in the preferred orientation
if the adapted peak moved away from the adapt angle, and ‘attrac-
tive’ shifts if the adapted peak moved towards the adapt angle (for
all figures negative peak shifts indicate repulsion). Figure 2A plots
peak shift as a function of the angle between the adaptor and the
nonadapted response peak. Our sample contained 32 cells (57%)
that showed significant repulsive shifts, 18 cells (32%) that showed
significant attractive shifts, and six cells (11%) that did not shift sig-
nificantly (P < 0.05; see Eqn 2 in Materials and methods). The pop-
ulation average peak shift was 2.81°. Previous studies that
Fig. 2. Effects of adaptation on orientation tuning. (A) The peak shift
presented control and adapted stimulus conditions in separate blocks induced by adaptation (ordinate) is plotted against the orientation difference
excluded units with large changes in orientation preference based on between the adapting grating and the control peak (abscissa). Negative peak
the suspicion that these changes reflect drifting isolation over time shift values indicate repulsion. The thick black line shows a 7.5°-wide sliding
(e.g. Wissig & Kohn, 2012). We did not exclude neurons based on window calculating the mean peak shift. Population mean peak shifts for
this criterion because our stimulus had adapted and nonadapted trials flank adapted (empty triangles) and end-of-flank adapted neurons (filled trian-
gles) are shown on the right. (B and C) show the normalized change in peak
randomly shuffled within the same session; therefore, if unit isola- height and baseline with the same format as A, respectively. Negative values
tion varied over time it would affect both types of trials equally. indicate decreased activity following adaptation. (D) Decreases in peak
Although adaptation could induce substantial attractive or repulsive height (ordinate) were larger than decreases in baseline (abscissa) for most
shifts in individual neurons, neither the main effect of adaptation neurons. Proportional changes in HWHM (E), and bandwidth (F) are shown
with the same format as A, but without the lines indicating sliding mean. For
(F1,54, P = 0.3) nor the flank interaction (F1,54, P = 0.96) were sig- all plots, open circles are flank adapted cells and filled circles are end-of-
nificant. Thus, our data from mouse differ from the consistent repul- flank adapted cells.
sion reported in previous cat and primate studies.
In contrast to the variable effects on the preferred orientation,
response amplitude was consistently reduced by adaptation. Changes should be smaller than the decrease in peak firing. The decrease in
in peak and baseline firing rates were both normalized to the non- peak firing was significantly larger than the decrease in baseline
adapted peak firing rate and negative numbers indicate suppression. (P = 2.8 9 104, paired t-test), which is more consistent with
Adaptation decreased peak height in all neurons, regardless of the divisive scaling.
relative angle between the adaptor and the nonadapted peak We used two complementary measures of tuning breadth: HWHM
(Fig. 2B); however, a 7.5°-wide sliding window calculating the depends predominantly on the width near the tuning curve’s peak,
mean normalized change in peak height (i.e. a boxcar filter) indi- whereas bandwidth was affected by the overall shape of the curve.
cates adaptation within ~20° of the nonadapted peak produced Both changes in tuning breadth were calculated as the proportional
slightly larger drops (solid line). Adaptation decreased baseline fir- difference, such that negative values indicated the curve became nar-
ing for all neurons in our sample, and the magnitude of this drop rower (HWHM; Fig. 2E) or less circular (bandwidth; Fig. 2F) fol-
appeared to be independent of the relative angle between the adaptor lowing adaptation. The main effect of adaptation was not significant
and the peak (Fig. 2C). This consistent suppressive effect was sup- for HWHM (F1,54, P = 0.74) or bandwidth (F1,54, P = 0.78). Nei-
ported by a significant main effect of adaptation for both peak ther HWHM (F1,54, P = 0.1) nor bandwidth (F1,54, P = 0.06) had
height (F1,54, P = 3.5 9 1011) and baseline (F1,54, P = 1.7 9 significant flank interactions (Fig. 2E and F). There was also no
1010). The flank interaction was not significant for peak height main effect of adaptation (F1,54, P = 0.48) or flank interaction
(F1,54, P = 0.99) or baseline (F1,54, P = 0.87). We then compared (F1,54, P = 0.42) for DIo.
the magnitude of suppressive effects on peak height and baseline for Orientation tuning curves in mouse V1 are generally broader and
each neuron in Fig. 2D. If the entire adapted curve was shifted less modulated than those in cat and macaque (Dr€ager, 1975; Wagor
downward, as if adaptation had a subtractive influence on firing, et al., 1980; Metin et al., 1988; Sohya et al., 2007; Niell & Stryker,
these two measures should be about equal. However, if adaptation 2008; Liu et al., 2009; Runyan et al., 2010; Tan et al., 2011; Kerlin
induced a divisive scaling of the adapted curve the drop in baseline et al., 2010), so we performed several additional analyses to

© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
European Journal of Neuroscience, 1–12
6 J. L. King and N. A. Crowder

Fig. 3. Potential influences on the direction and amplitude of peak shifts. (A) Histogram showing proportional differences between the firing rate at the peak
of the adapted curve and the control curve at that same angle (see inset diagram). All differences were negative indicating adapted curves always fell under con-
trol curves. (B) DIo (abscissa) plotted against peak shift (ordinate). Thick line in lower inset shows a 0.04-wide sliding window calculating the range of peak
shifts (window width depicted as a black rectangle with an arrow). (C) Bandwidth (abscissa) plotted against peak shift (ordinate) with the same format as B
(sliding window has a width of 2). (D) Normalized firing rate at the adapt angle (ordinate) plotted against the relative angle between nonadapted peak and
adapting orientation (abscissa). (E, F) Normalized change in peak height (E) or peak shift (F) is plotted against the normalized firing rate at the adapt angle
(now on the abscissa). The thick line in the lower insets shows a 0.04-wide sliding window calculating the range of peak drops (E) or peak shifts (F) for flank
adapted cells. Regression line (solid) and 95% confidence intervals (dashed) are shown in D–F. For all plots, open circles are flank adapted cells and filled cir-
cles are end-of-flank adapted cells.

determine whether this difference could account for the lack of con-
sistent repulsion in our data. Adapting cat V1 neurons, which have
narrower orientation tuning than mouse and even primate V1 cells
(Nauhaus et al., 2008), can induce facilitation at some orientations
such that the adapted curve shifts out from under the control curve
(Dragoi et al., 2001). This effect was never observed in our data,
and the histogram in Fig. 3A illustrates that the response at the
adapted peak was always smaller than the response at the identical
angle on the nonadapted curve. Given this constraint, large individ-
ual peak shifts in either direction could only be possible in cells
with broad tuning or large untuned responses. Both DIo (r = 0.02,
P = 0.84; Fig. 3B) and bandwidth (r = 0.05, P = 0.71; Fig. 3C)
were poorly correlated with peak shift, simply because individual
cells could show attractive or repulsive shifts. However, sliding win-
dows calculating the range of peak shifts (Fig. 3B and C bottom
insets) indicated that neurons with low DIo (those less modulated by
orientation) or low bandwidth values (more circular orientation tun-
ing) tend to have more variability in the size of their peak shifts.
The spike rate elicited by the adapting stimulus is critical for
other forms of adaptation in mouse V1 (LeDue et al., 2012, 2013;
King et al., 2016), so we examined the importance of response
magnitude on our measures of adaptation. Figure 3D shows that
responses to the adapting stimulus (normalized to the peak non-
adapted response) were more robust the closer the adapt angle was
to the peak of the nonadapted curve (Spearman rank correlation =
0.66, P = 4.24 9 108), as expected from orientation tuned cells.
The normalized spike rate elicited at the adapt angle was poorly cor-
related with the decrease in the adapted peak amplitude (Fig. 3E;
r = 0.03, P = 0.8) or peak shift (Fig. 3F; r = 0.09, P = 0.53). How-
ever, sliding windows calculating the range of both peak drops

Fig. 4. Adaptation over time. (A) Tuning curves from a sample neuron with responses averaged over the entire 2-s test period (format identical to Fig. 1). (B)
Neuron from A with responses divided into eight 250-ms epochs. Inset values indicate DIo of control (top) and adapted curves (bottom). (C) Average control
(filled circles) and adapted (empty circles) values of DIo over eight 250-ms epochs; values were normalized to the mean nonadapted DIo calculated over the
entire 2-s test. (D) Average peak orientation of control (filled circles) and adapted (empty circles) curves over eight 250-ms epochs with control curves aligned
to 0° at the first time bin. (E) Population histogram scoring the consistency of attraction/repulsion across epochs (see Results). (F) The peak shift (ordinate) in
the first 250-ms epoch plotted against the orientation difference between the adaptor and control peak (abscissa). The categorization of flank and end-of-flank
adaptation remained based on tuning curves averaged over the full 2-s stimulus duration. Format as in Fig. 2A. (G) Average peak height over epochs with all
responses normalized to the control peak height in the first epoch. (H) Average baseline over epochs with all responses normalized to the control peak height in
the first epoch. G and H follow format of D. All error bars indicate SEM.

© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
European Journal of Neuroscience, 1–12
 Orientation adaptation in mouse V1 7

© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
European Journal of Neuroscience, 1–12
8 J. L. King and N. A. Crowder

(Fig. 3E bottom inset) and peak shifts (Fig. 3F bottom inset) of
flank adapted cells show more variable adaptation effects with
higher elicited firing rates. Overall these additional analyses sug-
gested that the broader tuning of mouse V1 neurons may lead to lar-
ger or more variable peak shifts in either direction.
Dynamics of adaptation
Finally, we considered the possibility that subtle transient adaptation
effects could be masked by averaging spiking activity over the
entire 2-s test. Therefore, we examined how control and adapted ori-
entation tuning curves evolved over time by parsing responses into
250 ms epochs. We then calculated DIo and fit von Mises curves to
data from each epoch. We ran two-way repeated-measure ANOVAs
(with time epoch and adaptation as factors) to quantify changes in
DIo, peak location, peak height and baseline firing.
Figure 4A shows an example cell’s tuning curves averaged from
the entire 2-s test window, and Fig. 4B shows the eight 250-msec
epochs from the same cell. Both control and adapted tuning curves
changed in amplitude over time; however, the depth of tuning as
measured by DIo (Fig. 4B; noted top left inset of each graph)
remained relatively stable. For population data, control (filled cir-
cles) and adapted (empty circles) DIo values in each epoch were
normalized by the mean nonadapted DIo calculated using the fill 2-s
interval (Fig. 4C). We found that DIo changed significantly over
epochs (Fig. 4C; F1,7, P = 0.0002); however, the effect size was

Fig. 5. Modelling adaptation in cats and mice. (A) Model of how orientation tuned inputs may be combined in a pinwheel centre of cat V1. The flow diagram
on the left shows inputs under control (solid lines) or adapted conditions (dashed lines) that are first depicted as populations of excitatory (black) and inhibitory
(grey) curves (left-most boxes), which are summed to produce pooled inputs (middle boxes). Inhibition acts divisively, and then, the total input is passed
through a power-law nonlinearity (right-most box) to simulate orientation tuning curves (graph on right). (B) Histogram of peak shifts from 200 simulated cat
V1 pinwheel centre neurons generated as in A. (C and D) Simulation of adaptation in an iso-orientation domain of cat V1 with the same format as A and B.
Model parameters for simulations in A–D were: n = 50; hadapt = 12.5; u = 6; g = 0.5; hnom = 0; h = 5; d = 0.7; c = 0.3; p = 2; q = 0.7; Vthresh = 0.9;
w = 1.5; k1 = 0.5; k2 = 0.007. (E and F) Simulation of adaptation in mouse V1 with salt-and-pepper functional architecture in the same format as A and B (see
Results). Model parameters for this simulation were the same as A–D except: u = 3; Vthresh = 0.3. (G) Scatter column graph of individual (grey dots) and popu-
lation mean (horizontal black lines) peak shift values generated when we systematically varied the spiking threshold (Vthresh) while keeping all other model
parameters fixed. (H) Mean tuning breadth (HWHM) decreased when Vthresh was increased, regardless of the bandwidth parameter of excitatory inputs (u; noted
inset). (I) Scatter column graph of peak shift values generated when we systematically varied u while keeping all other parameters fixed (format as in G). Error
bars indicate 95% confidence intervals in G–I.

© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
European Journal of Neuroscience, 1–12
 Orientation adaptation in mouse V1 9

small (partial g2 = 0.07), and the direction of change varied over Modelling results
time. There was no evidence to support an effect of adaptation on
We generated a simplified feed-forward model of orientation adapta-
DIo (F1,1, P = 0.74), or an interaction between time epoch and
tion that first captured several salient features described in cat V1;
adaptation (F1,7, P = 0.12). We were concerned that the periodic fir-
then, in altering its features to align more with mouse V1, we nar-
ing of phase-sensitive neurons to the 2 Hz drifting gratings might
rowed down critical species differences that could explain our data.
have introduced variability into our DIo measures, but excluding
Adjacent neurons within cat V1 can have vastly different orientation
these cells did not affect the outcome of this analysis. Thus, we
preferences depending on their position within the orientation map,
found that the depth of orientation tuning for control and adapted
but anatomical studies show that their local dendritic arbours have a
curves changed inconsistently over time, similar to what was
circularly symmetrical geometry that extends approximately 500–
reported by Tan et al. (2011) with intracellular recordings.
800 lm into surrounding cortex independent of the somatic position
The mean preferred orientations (hpref) of control (filled circles)
(Malach et al., 1993; Das & Gilbert, 1999; Levy et al., 2014). Find-
and adapted (empty circles) curves across epochs are shown in
ings of broader orientation tuning at pinwheel centres (Nauhaus
Fig. 4D. We aligned cells with different preferred orientations by
et al., 2008), and more repulsion following adaptation (Dragoi
setting each nonadapted preferred orientation in the first epoch to
et al., 2001), have been hypothesized to arise from local network
zero. There was no evidence that preferred orientation changed
inputs that include many different preferred orientations. Conversely,
over epochs (F1,7, P = 0.75), that adaptation consistently induced
the more homogenous local network inputs in iso-orientation
repulsive or attractive peak shifts (F1,1, P = 0.87), or of an interac-
domains are thought to give rise to narrower orientation tuning and
tion between epoch and adaptation (F1,7, P = 0.74). We also
little repulsion following adaptation. We simulated adaptation in cat
implemented a scoring system to determine whether individual
V1 cells located near a pinwheel centre by pooling excitatory inputs
neurons consistently showed repulsion or attraction over epochs by
with preferred orientations (hi) that varied widely ( 60–90°) from
assigning a value of 0 to each epoch with an attractive shift and 1
the simulated neuron’s preferred orientation (hnom). Figure 5A
to each epoch with a repulsive shift (Fig. 4E). Here, a hypothetical
shows the simulation of a single neuron that pools multiple inputs
neuron that showed repulsive peak shifts in all epochs would have
(left-most boxes) to generate an orientation tuned spiking response
a score of 8. We performed a Hartigan’s dip test on the scores
(graph on right; solid line) that undergoes a repulsive peak shift fol-
and rejected the null hypothesis of unimodality (P < 0.05; Hartigan
lowing adaptation (dotted line). Figure 5B shows a population peak-
& Hartigan, 1985), which suggests that most cells were fairly con-
shift histogram of 200 simulated neurons indicating repulsion is
sistent in their attraction or repulsion over epochs. Averaging
common under these model conditions. Individual simulated cat V1
across neurons in each epoch may have masked an interaction
neurons located near iso-orientation domains (hi  10–20° from
between the adaptor angle and peak shift, so Fig. 4F plots individ-
hnom) were also orientation tuned (Fig. 5C), but rarely showed
ual peak shifts in the first epoch (when adaptation is expected to
repulsion (Fig. 5D). The modelling above simulated the main results
be strongest) as a function of the angle between the adaptor and
of Dragoi et al. (2001), with repulsion at pinwheel centres but not
the nonadapted response peak in the same format as Fig. 2A. Like
at iso-orientation domains; however, our model also inherently
the data derived from the full 2-s window, both repulsive and
caused the nonadapted curves of pinwheel neurons to have ~18%
attractive shifts are evident, but there was no evidence of a main
broader orientation tuning than iso-orientation domain neurons,
effect of adaptation on peak shift (F1,54, P = 0.81) or a flank inter-
which simulated the results of Nauhaus et al. (2008). Note that in
action (F1,54, P = 0.81). Overall, the pattern of results for peak
Fig. 5A and C adaptation caused peak height to decrease (as in our
shifts evolving over time was similar to our time-averaged analysis
data; Wissig & Kohn, 2012; Patterson et al., 2013), but this could
in that individual cells could show repulsion or attraction but nei-
be prevented (to mimic the data of Dragoi et al., 2001) by changing
ther shift direction was dominant.
the gain of adaptation for inhibitory inputs and activity-dependent
The peak amplitude (a) and baseline (m) parameters of the tuning
hyperpolarization (data not shown).
curves followed the classic evolution of visually evoked responses
To simulate adaptation in mouse V1 neurons, we modified our
over time: they reached a transient peak early in the response before
model of cat V1 cells located at pinwheel centres. The salt-and-pep-
undergoing exponential decay (Albrecht et al., 1984). Figure 4G
per organization of mouse V1 suggests that local cortical networks
shows the mean peak amplitude of control (filled circles) and
here will also contain neurons with diverse orientation tuning like
adapted (empty circles) curves across epochs, and Fig. 4H shows
the pinwheel centres of cat V1 (Malach et al., 1993; Levy et al.,
the mean baseline data across the same time bins. For individual
2014; Fig. 5E, left-most boxes). To simulate the broader orientation
cells, both peak height and baseline were normalized by the peak
tuning and poorer modulation we observed in our mouse data, we
amplitude of the nonadapted curve in the first epoch. Population
made two changes to our model: (1) we lowered the spike threshold
means for both peak amplitude and baseline were maximal in the
(Vthresh) so that simulated spike-rate orientation curves had an
second epoch, which was consistent with the example cell in
untuned component (Fig. 5E, graph on right); and (2) we made the
Fig. 4B. Mean firing in the first epoch was likely lower because it
tuning of the excitatory inputs broader (i.e. smaller values of u).
included the latent period (median latency: 61 ms; interquartile
With these changes, the distribution of peak shifts in our simulated
range = 39–98 ms). Peak amplitude varied significantly with epoch
population became wider, there were more instances of attractive
(F1,7, P = 5.4 9 1011) and adaptation (F1,1, P = 3.1 9 1011);
peak shifts, and the mean peak shift was closer to zero (Fig. 5F).
however, the interaction did not reach significance (F1,7, P = 0.33).
Systematically changing the spike threshold while keeping all other
Baseline also varied significantly with epoch (F1,7, P = 1.6 9
parameters the same did not have any consistent effect on the distri-
1022) and adaptation (F1,1, P = 7.8 9 109), but here the interac-
bution of peak shifts (Fig. 5G), although raising the spike threshold
tion was also significant (F1,7, P = 1.7 9 1010) suggesting that for
did lead to narrower tuning (Fig. 5H). Conversely, systematically
this parameter the effect of adaptation was diminished towards the
increasing the tuning breadth of excitatory inputs while keeping all
end of the 2-s test period. Once again, the consistent effect of adap-
other parameters the same caused more instances of attraction and
tation on peak amplitude and baseline seen in the time-binned
the distribution of peak shifts to approach zero (Fig. 5I). Thus, our
results matched our time-averaged analysis closely.

© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
European Journal of Neuroscience, 1–12
10 J. L. King and N. A. Crowder
model suggests that it was the broader orientation tuning of mouse
V1 neurons that led adaptation to produce relatively more attractive
peak shifts in our data set than observed in other species.
Discussion
The change in the orientation tuning of V1 neurons following pro-
longed exposure to a single orientation is a well-known example of
adaptation that has been studied in classical animal models of vision
(cats: Priebe et al., 2010; Bachatene et al., 2012; Cattan et al.,
2014; monkeys: Wissig & Kohn, 2012; Patterson et al., 2013) and
is a potential neural correlate of the tilt-after-effect and related illu-
sions (Gibson & Radner, 1937; Levinson & Sekuler, 1976; Patterson
& Becker, 1996; Schrater & Simoncelli, 1998; Clifford, 2002). We
used a comparative approach by studying orientation adaptation in
mouse V1, which possesses orientation tuned neurons but differs
from classical models in its functional architecture and proportion of
highly orientation selective neurons. Unlike the mainly repulsive
shifts seen in past work, we found adaptation produced approxi-
mately a 2 : 1 proportion of repulsive vs. attractive shifts. Adapta-
tion also consistently attenuated responses across all orientations.
We first consider whether these differences from past work reflect
procedural variations or a true species difference and then discuss
implications for studying this phenomenon in mice.
Procedural vs. species differences
As described in the Results section, our sample of mouse V1 neu-
rons was similar to previous mouse V1 surveys in terms of the pro-
portion of orientation selective units and tuning breadth.
Approximately 11% of the units in our sample were phase sensi-
tive, which is higher than the 6% reported by Gao et al. (2010),
but lower than the ~35–50% reported in other studies (Niell &
Stryker, 2008; Van den Bergh et al., 2010). However, both phase-
sensitive and phase-invariant units showed adaptation in our sample
as well as in previous cat and primate work (Dragoi et al., 2001;
Wissig & Kohn, 2012; Patterson et al., 2013), so the composition
of our sample seems unlikely to have led to the observed differ-
ences in adaptation.
Our stimuli were also similar enough to previous work that is
unlikely that the differences we observed were due to our adaptation
protocol. Regarding stimulus timing, past work in cats and primates
has shown that flank adaptation within the classical receptive field
has consistently yielded repulsive peak shifts with adaptation times
ranging from 50 ms to 10 min (Dragoi & Sur, 2000; Felson et al.,
2002; Patterson et al., 2013). Furthermore, repulsive shifts were
observed whether adaptation was induced with randomly interleaved
adaptation/control trials or with a top-up protocol (Patterson et al.,
2013). However, several studies in opioid- anaesthetized macaques
have shown that the spatial parameters of the stimulus protocol can
affect the type of adaptation observed. Large stimuli that extend into
the extra-classical receptive fields of most V1 neurons produced
attractive rather than repulsive peak shifts (Kohn & Movshon, 2004;
Wissig & Kohn, 2012; Patterson et al., 2013). We are sceptical that
this extra-classical effect was the source of attractive shifts in our
data set for three reasons. First, our online analysis helped us limit
the adaptation stimuli to the classical receptive field. Second, it has
been reported that isoflurane/urethane anaesthesia decreases surround
suppression in mice (Adesnik et al., 2012; Vaiceliunaite et al.,
2013), so if the adaptation stimuli did inadvertently extend beyond
the receptive field any extra-classical modulation would have been
weakened by our isoflurane anaesthesia. Third, in the primate work,
© 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd
attractive shifts were often accompanied by response facilitation
(Wissig & Kohn, 2012), whereas all of our cells showed suppres-
sion. Overall, our interleaved stimulus protocol with 2-s adaptors
targeting the classical receptive field could reasonably be predicted
to produce consistent repulsion in cats or primates, so the higher
proportion of attraction in our data set appears to be a genuine spe-
cies difference.
There are several differences in the way mouse V1 deals with ori-
entation signals that may underlie our observed differences in adap-
tation: (1) there is more sharpening of orientation selectivity
between the dLGN and V1 in cats (Scholl et al., 2013); (2) mice
have a greater proportion of neurons that are nonselective or poorly
tuned for orientation (Niell & Stryker, 2008; Gao et al., 2010; Liu
et al., 2011; Tan et al., 2011; Stroud et al., 2012); and (3) mice
have salt-and-pepper functional architecture rather than an ordered
orientation map (Ohki et al., 2005). Our model, which focused on
the latter two differences, suggested it was the broader orientation
tuning of inputs to mouse V1 cells that could lead to our observed
pattern of peak shifts. Additional evidence that tuning breadth can
lead to species differences in adaptation comes from nonoriented V1
neurons. All of our nonoriented mouse cells showed broad response
reduction following adaptation, as if they were fed by essentially
untuned inputs. Conversely, Wissig & Kohn (2012) showed that
their mean population tuning curve of nonoriented primate V1 neu-
rons developed a ‘dent’ at the adapting angle, as if these cells were
pooling over multiple tightly tuned inputs.
Studying adaptation to orientation in the mouse
There is currently a poor understanding of what types of changes in
neural responding underlie the perceptual tilt-after-effect illusion.
Models of V1 adaptation where each orientation tuned cell acts as a
labelled line predict that repulsive neural peak shifts actually lead to
perceptual attraction (e.g. Gilbert & Wiesel, 1990; Kohn & Mov-
shon, 2004), but decreases in gain, broadening of orientation tuning,
adapting surround suppression, or processing in subsequent brain
areas could counteract this effect (Clifford et al., 2001; Sur et al.,
2002; Kohn & Movshon, 2004; Wissig & Kohn, 2012). There are
several potential strategies that could be used to clarify links
between neurophysiological and perceptual aspects of adaptation that
require developing new methodologies.
If the repulsive shifts in orientation tuning observed in past cat
and primate work are indeed the neural basis for the tilt-after-effect
illusion, our current electrophysiological findings suggest that this
illusion should not occur in mice. This would mean that the genetic
tools available in mice, which are accelerating the visual neuro-
science community’s ability to monitor large neural populations and
dissect neural circuits (Baker, 2013), could not be brought to bear
on this psychophysically well characterized illusion (Gibson & Rad-
ner, 1937; Levinson & Sekuler, 1976; Patterson & Becker, 1996;
Schrater & Simoncelli, 1998; Clifford, 2002). Thus, it seems the
most straightforward way to determine whether this line of research
should continue in the mouse is to psychophysically test whether
mice perceive the tilt-after-effect. This proposal is challenging on
several fronts. Whereas other fields of neuroscience have established
behavioural tests in rodents that are mediated by vision (e.g. ele-
vated plus maze for anxiety: Pellow et al., 1985; Barnes maze for
memory and spatial learning: Barnes, 1979), rigorous psychophysi-
cal tests to probe perceptual decision making are not yet as devel-
oped in mice as they are in primates (Carandini & Churchland,
2013; c.f. Busse et al., 2011; Histed et al., 2012). So far, it has
been shown that mice are able to coarsely discriminate different
European Journal of Neuroscience, 1–12

orientations (Reuter, 1987; Andermann et al., 2010; Pinto et al.,
2013; Long et al., 2015); however, these types of discrimination
task would need to be altered to work in an adaptation paradigm.
Linking neural activity with perception will be even more challeng-
ing. For comparison, there is a much longer history of testing fine-
grain perceptual discrimination in primates (e.g. Newsome & Pare,
1988), but primate studies of adaptation that examine both a change
in neural activity and a change in perception/behaviour are quite rare
(Kohn, 2007; Yang & Lisberger, 2009). In fact, although neural
adaptation to orientation has been studied in awake primates (Gut-
nisky & Dragoi, 2008; Wang et al., 2011), we are not aware of any
work that has linked altered perception of orientation with changes
in neural encoding. In summary, whereas our electrophysiological
data suggest that neurons across mouse V1 adapt to orientation dif-
ferently than V1 neurons of primates or cats, deciding whether or
not these differences are actually important will require the develop-
ment of novel psychophysical tests in multiple species to link neural
adaptation with perception.
Acknowledgements
The authors thank Matthew P. Lowe for assistance with data collection. This
work was supported by the Natural Sciences and Engineering Research
Council of Canada.
Conflicts of interest
The authors declare that they have no conflicts of interest in association with
this work.
Author contributions
J.L.K. and N.A.C. collected and analysed data; J.L.K. and N.A.C. interpreted
results of the experiments; J.L.K. and N.A.C. wrote and revised the manu-
script; N.A.C. conceived and designed the research; J.L.K. prepared figures;
J.L.K. and N.A.C. approved the final version of the manuscript.
Data accessibility
Access to supporting data and materials may be arranged by contacting the
corresponding author.
Abbreviations
DIgrating, discrimination index for gratings; DIo, discrimination index for ori-
entation; dLGN, dorsal lateral geniculate nucleus; HWHM, half-width at half
maximum; ISI, interstimulus interval; RF, receptive field; SF, spatial fre-
quency; TF, temporal frequency; TTL, transistor-transistor logic; V1, primary
visual cortex.
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