Temporal Contrast Adaptation in Salamander Bipolar Cells Fred Rieke

Temporal Contrast Adaptation in Salamander Bipolar Cells Fred Rieke
The Journal of Neuroscience, December 1, 2001, 21(23):9445–9454
Temporal Contrast Adaptation in Salamander Bipolar Cells
Fred Rieke
Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195
This work investigates how the light responses of salamander
bipolar cells adapt to changes in temporal contrast: changes in
the depth of the temporal fluctuations in light intensity about the
mean. Contrast affected the sensitivity of bipolar cells but not of
photoreceptors or horizontal cells, suggesting that adaptation
occurred in signal transfer from photoreceptors to bipolars.
This suggestion was confirmed by recording from photoreceptor–bipolar pairs and observing a direct dependence of the gain
of signal transfer on the contrast of the light input. After an
increase in contrast, the onset of adaptation in the bipolar cell
had a time constant of 1–2 sec, similar to a fast component of
contrast adaptation in the light responses of retinal ganglion
cells (Kim and Rieke, 2001). Contrast adaptation was mediated
by processes in the dendrites of both ON and OFF bipolars. The
functional properties of adaptation differed for the two bipolar
types, however, with contrast having a much more pronounced
effect on the kinetics of the responses of OFF cells than ON cells.
A general problem sensory neurons face is adjusting their operational range to match the range of the input signals they receive.
This is particularly clear for vision, in which the mean light
intensity and the contrast (the extent of fluctuations in light
intensity about the mean) vary substantially in different visual
environments. The visual system handles these differences in
input signals by adjusting its sensitivity, or adapting. Adaptation
includes mechanisms sensitive to the mean light intensity (for
review, see Walraven et al., 1990) and the spatial and temporal
contrast (for review, see Shapley, 1997; Meister and Berry, 1999).
This work examines the contribution of retinal bipolar cells to
temporal contrast adaptation.
Contrast adaptation is widely viewed as a cortical phenomena,
and there is good evidence that cortical mechanisms contribute
(Albrecht et al., 1984; Ohzawa et al. 1985; Sanchez-Vives et al.,
2000). Several studies, however, show that changes in temporal
contrast affect the sensitivity of retinal ganglion cells in amphibians and mammals (Sakai et al., 1995; Smirnakis et al., 1997),
including primate (Chander and Chichilnisky, 1999, 2001). Indeed, without contrast adaptation, many retinal neurons would be
easily saturated because of their high contrast gain (Capovilla et
al., 1987; Burkhardt and Fahey, 1998, 1999). Thus, the retina
makes an important contribution to the ability of the visual to
adapt to contrast. We know little, however, about where contrast
adaptation occurs in the retina or what mechanisms are
responsible.
Retinal contrast adaptation shows a range of spatial and temporal properties: the spatial extent of the signal controlling contrast adaptation differs between ON and OFF ganglion cells (Smirnakis et al., 1997); the onset of adaptation after an increase in
contrast has several temporal components (Victor, 1987; Sakai et
al., 1995; Smirnakis et al., 1997; Kim and Rieke, 2001); and the
strength of contrast adaptation differs between ON and OFF ganglion cells (Chander and Chichilnisky, 1999; Kim and Rieke,
2001). This diversity in the properties of contrast adaptation in
the retinal output suggests a corresponding diversity in both the
mechanisms mediating contrast adaptation and in the functional
roles of each mechanism.
We found previously that contrast adaptation included contributions from spike generation in retinal ganglion cells and from
unidentified sites within the retinal circuitry (Kim and Rieke,
2001). The aim of the present work was to identify the sites of
contrast adaptation in the retinal circuitry and the mechanisms
responsible. The principal findings described here are as follows:
(1) the first site of contrast adaptation in the retina is in the
dendrites of bipolar cells; (2) this site contributes to the fast-onset
component of contrast adaptation seen in retinal ganglion cells
(Kim and Rieke, 2001); and (3) the functional properties of
contrast adaptation differ between ON and OFF bipolars, with
contrast exerting a larger effect on the kinetics of the responses of
OFF cells than ON cells.
Received March 6, 2001; revised Sept. 10, 2001; accepted Sept. 13, 2001.
This work was supported by National Institutes of Health Grant EY-11850 and the
McKnight Foundation. I thank Cecilia Armstrong, Divya Chander, E. J. Chichilnisky, Greg Field, Josh Gold, Kerry Kim, and Maria McKinley for helpful discussions
and Eric Martinson for excellent technical assistance.
Correspondence should be addressed to Dr. Fred Rieke at the above address.
E-mail: [email protected]
Copyright © 2001 Society for Neuroscience 0270-6474/01/219445-10$15.00/0
Key words: contrast gain control; contrast adaptation; bipolar
cell; adaptation; temporal contrast; retinal signal processing
MATERIALS AND METHODS
Recording procedures. All experiments used retinas from larval tiger
salamanders (Ambystoma tigrinum; from Charles Sullivan, Nashville,
TN). Salamanders were dark adapted overnight, and retinas were isolated under infrared light (K im and Rieke, 2001) following procedures
approved by the Administrative Panel on Laboratory Animal C are at the
University of Washington.
Light-evoked current and voltage responses of retinal cells were measured in a slice preparation. A piece of retina ⬃1 ⫻ 2 mm was embedded
in low gelling temperature agar (Sigma, St. L ouis, MO), immersed in
cold H EPES-buffered Ames medium (Sigma), and sliced in 300-␮mthick sections on a vibrating microtome (Leica, Wetzlar, Germany).
Slices were transferred to a recording chamber and held in place with a
coarse nylon grid glued to a platinum weighting ring. The chamber was
placed on the stage of an upright microscope equipped with an infrared
viewing system. Slices were continuously superf used with a bicarbonate
Ringer’s solution containing (in mM): 110 NaC l, 2 KC l, 30 NaHC O3, 1.5
C aC l2, 1.6 MgC l2, and 10 glucose; pH was 7.4 when equilibrated with 5%
C O2–95% O2 and osmolarity was 270 –275 mOsm. The volume of the
recording chamber was ⬃300 ␮l, and the superf usion rate was 1–2
ml /min. All experiments were at 20 –22°C.
9446 J. Neurosci., December 1, 2001, 21(23):9445–9454
Light produced by a light-emitting diode (L ED) was focussed on the
slice through the bottom of the recording chamber. An L ED with a peak
output at 470 nm was used to stimulate rods, and one with a peak output
at 640 nm was used to stimulate L cones. The light stimuli were spatially
uniform and illuminated a circular area 650 ␮m in diameter centered on
the recorded cell. The temporal contrast of the light stimulus was controlled by adding Gaussian fluctuations to the signal controlling the light
output of the L ED. The Gaussian fluctuations were low-pass filtered at
either 10 (for rods) or 30 (for cones) Hz, as noted in the figure legends.
The contrast of this stimulus was defined as the SD of the light intensity
divided by the mean. Light intensities measured at the preparation are
given in the figure legends.
Electrical responses were measured using either perforated-patch or
whole-cell recordings and an Axopatch 200B patch-clamp amplifier
(Axon Instruments, Foster C ity, CA); recording configurations are noted
in the figure legends. Patch pipettes were filled with an internal solution
containing (in mM): 125 K-aspartate, 10 KC l, 10 H EPES, 5 Nmethylglucamine (NMG)–N-hydroxyethylethylenediaminetriacetic acid
(H EDTA), 1 C aC l2, 1 ATP, 0.1 GTP, and 0.1 mM calcein, pH was
adjusted to 7.2 with NMG-OH (and osmolarity was 260 –265 mOsm). For
perforated-patch recordings, the pipette solution also contained 1 mg /ml
amphotericin-B (solubilized formulation; Sigma), and the pipette tip was
filled with amphotericin-free solution. Filled pipettes had resistances of
8 –10 M⍀, and the series resistance during recording was 20 – 40 M⍀.
C alcein was included in the pipette solution to permit the morphology of
a cell to be visualized under fluorescence at the end of a recording; all
bipolar cells reported here had processes in both the inner and outer
plexiform layers. ON and OFF bipolars were distinguished based on the
polarity of their responses to 1 sec light increments and decrements (see
Fig. 6, insets). In voltage-clamp recordings, bipolar cells were held at ⫺60
mV; in current-clamp recordings, the holding current was between 0 and
⫺50 pA, resulting in a membrane potential near ⫺50 mV. Voltages have
not been corrected for junction potentials (approximately ⫺9 to ⫺10 mV
for the solutions used).
Data anal ysis. The effect of contrast on the amplitude and kinetics of
the light response of a cell was measured using a static nonlinearity
model that provided a relatively simple description of how continuous
light inputs were transformed into cellular responses (Sakai et al., 1995;
Chichilnisky, 2001). An important aspect of this model is that it separates
an instantaneous nonlinearity in the response of a cell (e.g., attributable
to saturation or activation of voltage-dependent conductances) from a
change in the response characteristics of a cell attributable to adaptation.
The model describes the current-to-response transformation as a linear
filter followed by a static or time-independent nonlinearity (Fig. 1 A).
Comparing the filter and static nonlinearity for lights of different contrasts proved an effective means of characterizing contrast-dependent
changes in the amplitude and kinetics of the light response of a cell.
Details of the calculation of the linear filter and static nonlinearity are
described by K im and Rieke (2001).
The linear filter and static nonlinearity were determined from recordings of 5–10 min of the response of a cell to light inputs of a given
contrast. Figure 1 shows an example of this analysis for responses of a
current-clamped ON bipolar cell to a 30% contrast light input. Figure 1 B
shows the linear filter; convolving this filter with the light input provides
the best linear estimate of the voltage response of a cell given the light
input (Wiener, 1949; K im and Rieke, 2001). Thus, the shape of the filter
estimates the time course of the response of a cell to a brief light flash at
time 0 in the presence of the fluctuating contrast signal. For ON cells such
as that in Figure 1 B, the linear filter measured under current clamp has
a positive polarity, reflecting the depolarization produced by an increment in light intensity (Fig. 1 B, inset). Systematic differences between the
measured voltage and the linear prediction obtained by convolving the
light input with the linear filter were used to determine a timeindependent nonlinearity in the relationship between light input and the
response of a cell: the static nonlinearity in the model. The shape of the
static nonlinearity was determined by calculating the average measured
response for each value of the linear prediction. Figure 1C plots the
average measured response ( y-axis) against the corresponding linear
prediction (x-axis). In this cell, as in most bipolars, the nonlinearity was
mild and consisted primarily of a gradual decrease in slope for large
response amplitudes.
Figure 1 D compares a short section of the measured voltage response
with the prediction from the linear filter and static nonlinearity in Figure
1, B and C. Although the prediction captures much of the structure in the
measured response, there are also clear differences. In principle, these
Rieke • Temporal Contrast Adaptation in Bipolar Cells
Figure 1. Static-nonlinearity model. A, The transformation between light
inputs and cellular response was described using a model consisting of a
linear filter followed by a time-independent or static nonlinearity. The
filter and static nonlinearity were calculated from recordings of 5–10 min
of the response of a cell to a fluctuating light input. B, Linear filter for a
current-clamped ON bipolar cell stimulated with a 30% contrast light
input. The inset shows the response of a cell to a 1 sec light step. C, Static
nonlinearity determined by plotting the measured response against the
linear prediction formed by convolving the light input with the linear filter
in B. Each point represents the average measured current ( y-axis) for a
particular value of the linear prediction (x-axis). Error bars are SE and are
mostly obscured by the data points. D, Short section of the measured and
predicted response. Mean light intensity, 20,300 photons ␮m ⫺2 sec ⫺1
using 640 nm LED; bandwidth, 0 –30 Hz. Holding current, 0 pA.
Perforated-patch recording.
differences could reflect either noise in the measured response or a
failure of the model. To distinguish between these possibilities, differences in the individual measured responses to a repeated stimulus were
compared with differences between the measured and predicted response. The extent of trial-to-trial fluctuations in the response of a cell
was determined by measuring the correlation between the average response and the individual responses to 15–30 repeats of a 20 sec stimulus.
In four such experiments, the average correlation was 0.76. This correlation was compared with the average correlation between the response
predicted by the static nonlinearity model and the individual measured
responses, which was 0.70 in the same four cells. Thus, ⬎90% of the
light-dependent structure in the measured response was well predicted by
the static nonlinearity model.
The model of Figure 1 was used to study contrast adaptation by
comparing linear filters and static nonlinearities measured for light
inputs of two contrasts. In all cells analyzed, the effect of contrast could
be restricted to changes in the linear filter, greatly simplif ying interpretation of the results. For a given contrast, the linear filter and static
nonlinearity are unique up to a single scale factor. Thus, both the y-axis
scaling of the filter in Figure 1 B and the x-axis scaling of the static
nonlinearity in Figure 1C can be multiplied by a factor ␣ without
changing the prediction of the model, because the rescaling of the filter
amplitude is offset by the change in the static nonlinearity. When linear
Rieke • Temporal Contrast Adaptation in Bipolar Cells
J. Neurosci., December 1, 2001, 21(23):9445–9454 9447
filters and static nonlinearities for two contrasts were compared, ␣ was
chosen to produce the best overlap of the static nonlinearities (Chichilnisky, 2001; K im and Rieke, 2001). For example, Figure 3D –F shows
nonlinearities for a cone, horizontal cell, and OFF bipolar cell measured
at 10 and 30% contrast. In each case, ␣ was chosen to cause the static
nonlinearities to overlap and thus restrict the effect of contrast to changes
in the linear filter. A similar scaling was used each time contrast adaptation was quantified using the static nonlinearity model. Thus, the
transformation of light inputs into cellular responses was described as a
contrast-dependent linear filter followed by a contrast-independent static
nonlinearity.
RESULTS
The experiments described below indicate that signal transfer
from rods and cones to bipolar cells provides the first site of
contrast adaptation in the retina. The onset and offset of this
adaptation were relatively rapid and contributed to a fast-onset
component of contrast adaptation in retinal ganglion cells. Contrast adaptation differed both functionally and mechanistically in
ON and OFF bipolars.
Bipolar cells provide the first site of
contrast adaptation
Two results indicate that the light responses of bipolar cells adapt
to the contrast of the light input but that those of photoreceptors
and horizontal cells do not. First, after an increase in contrast, the
amplitude of the light response of a bipolar immediately increased and then gradually declined, suggesting a time-dependent
change in sensitivity induced by the contrast change. Second, the
steady-state sensitivity of the light responses of bipolar cells
decreased after an increase in contrast. Both effects were small or
absent in photoreceptors and horizontal cells.
Response time course after a change in contrast
A signature of adaptation is a change in sensitivity over time after
a change in the input signal. Thus, contrast adaptation should
cause gradual changes in the amplitude of the response of a cell
after a change in contrast. To test for such changes, a randomly
fluctuating light stimulus was switched between 10 and 30%
contrast every 20 sec while recording the resulting response in a
photoreceptor, horizontal cell, or bipolar cell. Figure 2 A–C
shows voltage recordings from a cone ( A), horizontal cell ( B),
and OFF bipolar cell ( C) to a single cycle of this alternating
contrast signal. The timing of the contrast change is shown in the
stimulus trace at the bottom of the figure.
The amplitude of the light responses of photoreceptors and
horizontal cells changed quickly after an increase (0 sec) or
decrease (20 sec) in contrast and did not show time-dependent
structure that would suggest the cells were adapting. The absence
of time-dependent structure was captured more clearly by measuring the time-dependent variance across 15–30 cycles of the
contrast signal. Independent stimuli were used in each cycle, and
thus the variance measured the strength of the response of a cell
to the fluctuating stimulus. In both photoreceptors (Fig. 2 D) and
horizontal cells (Fig. 2 E), the variance reached a steady-state
level within ⬃0.2 sec after a change in contrast and maintained
this level throughout the 20 sec duration of the contrast signal. A
similar lack of time dependence was observed in the responses of
four rods, eight cones, and six horizontal cells.
The responses of bipolar cells, on the other hand, did show
time-dependent structure. After an increase in contrast, the amplitude (Fig. 2C) and the variance (Fig. 2 F) of the response
increased rapidly and then declined to a steady level; after a
decrease in contrast, the variance fell to an initial minimum and
Figure 2. Cone, horizontal, and bipolar responses to an alternating
contrast signal. The stimulus alternated between 30 and 10% contrast
every 20 sec (see stimulus trace at bottom). Current-clamp responses to a
single cycle of this stimulus are shown in A for a cone, B for a horizontal
cell, and C for an OFF bipolar cell. The time dependence of the amplitude
of the response of each cell to the fluctuating contrast stimulus was
measured by calculating the time-dependent variance from 15–30 cycles
of the stimulus. The fluctuating stimulus was independent in each cycle.
The variance is shown in D for the cone, E for the horizontal cell, and F
for the bipolar. The variance measured in the cone and horizontal cell
showed little time-dependent structure after a change in contrast, whereas
the variance measured in the bipolar cell showed transients after increases
(at t ⫽ 0) and decreases (at t ⫽ 20 sec) in contrast. Mean light intensity,
18,800 photons ␮m ⫺2 sec ⫺1 for the cone and bipolar cell and 18,200
photons ␮m ⫺2 sec ⫺1 for the horizontal cell (all using 640 nm LED).
Holding currents: ⫺50 pA for the cone, 0 pA for the horizontal, and 0 pA
for the bipolar. Perforated-patch recordings.
then gradually increased. A similar time dependence was observed in nine bipolar cells. These results suggest that bipolar
cells adapt to temporal contrast.
Contrast-dependent changes in sensitivity
The static nonlinearity model (see Materials and Methods) (Fig.
1) was used to determine how contrast affected the gain and
kinetics of the responses of photoreceptors, horizontal cells, and
bipolar cells. This model predicts the response of a cell to continuous light inputs of a particular contrast by passing the light
intensity through a linear filter followed by a time-independent or
static nonlinearity (Fig. 1). The linear filter (Fig. 3A) estimates
the time course of the response of a cell to a brief light flash in the
presence of a fluctuating contrast signal. Thus, for the cone in
Figure 3A, the filter predicts that the cell would respond to a brief
light flash at time 0 with a hyperpolarization lasting ⬃0.2 sec. The
static nonlinearity (Fig. 3D) describes the relationship between
the output of this linear filter and the measured response. In
general, this relationship is nonlinear, reflecting processes such as
saturation or activation of cellular conductances. This model
provided a relatively compact description (a single filter and
time-independent nonlinearity) of how the cell responded to light
inputs of a particular contrast. A key aspect of this model is that
it separates instantaneous nonlinearities in the response of a cell
from changes in sensitivity attributable to adaptation.
Contrast-dependent changes in the amplitude and kinetics of
the response of a cell were measured by comparing filters and
nonlinearities for different contrast inputs. High- and low-contrast
stimuli were interleaved to ensure that adaptation was reversible.
A section of record after each change in contrast was discarded to
9448 J. Neurosci., December 1, 2001, 21(23):9445–9454
Figure 3. Contrast adaptation in a current-clamped cone, horizontal cell,
and OFF bipolar cell measured using the static nonlinearity model. Same
cells and recording conditions as Figure 2. The contrast was alternated
between 10 and 30% every 20 sec. Linear filters and static nonlinearities
were calculated from 15–30 cycles of this stimulus, excluding the first 4 sec
of record after a change in contrast. Linear filters measured for 10% (thick
trace) and 30% (thin trace) contrast stimuli are shown in A for the cone,
B for the horizontal cell, and C for the OFF bipolar cell. Static nonlinearities are shown in D for the cone, E for the horizontal cell, and F for the
bipolar cell. In each case, the static nonlinearities at 10 and 30% contrast
overlapped and hence did not contribute to contrast adaptation. Linear
filters at 10 and 30% contrast were similar in the cone and horizontal cell
but differed substantially in the bipolar.
permit the response of a cell to reach steady state. Figure 3A–C
shows linear filters measured at 10 and 30% contrast for the cone,
horizontal cell, and OFF bipolar cell from Figure 2. Figure 3D–F
plots the corresponding static nonlinearities. In each cell, the
nonlinearities had similar shapes at high and low contrast and
thus did not contribute to contrast-dependent changes in sensitivity (see Materials and Methods). A similar contrast independence of the shape of the static nonlinearity was found in all of
the photoreceptors, horizontal cells, and bipolar cells studied.
This greatly simplified characterization of contrast adaptation as
the effect of contrast on the response of a cell was restricted to
changes in the linear filter. In subsequent figures, the static
nonlinearities are not shown, and the linear filters at high and low
contrast are scaled by a common factor so that the filter at low
contrast has unit amplitude.
Linear filters measured at 10 and 30% contrast were nearly
identical in cones (Fig. 3A) and horizontal cells (Fig. 3B) but
differed considerably in bipolar cells (Fig. 3C). The ratio of the
amplitude of the filter at high and low contrast was 0.98 ⫾ 0.04
(mean ⫾ SEM) in four rods, 1.01 ⫾ 0.04 in eight cones, 0.96 ⫾
0.03 in six horizontal cells, and 0.79 ⫾ 0.02 in 42 bipolar cells.
Contrast had a similar effect on the light responses of current- and
voltage-clamped bipolar cells (see Fig. 8); thus, in most experiments, cells were voltage clamped to minimize the effects of
voltage-activated conductances. Experiments like those illustrated in Figure 3 show that the sensitivity of photoreceptors and
horizontal cells changed little after a change in contrast, whereas
the sensitivity of bipolar cells changed substantially.
Contrast affects the gain of photoreceptor–bipolar
signal transfer
The experiments of Figures 2 and 3 indicate that bipolar cells, but
not photoreceptors or horizontal cells, adapt to temporal con-
Rieke • Temporal Contrast Adaptation in Bipolar Cells
Figure 4. Contrast affected gain of signal transfer from photoreceptors
to bipolars. The gain of signal transfer was measured by injecting depolarizing current into the photoreceptor and measuring the resulting
postsynaptic response in the bipolar cell. This was repeated in the presence and absence of a 25% contrast light input. A, Measurements from a
current-clamped cone and voltage-clamped ON bipolar cell. The cone
current was stepped from ⫺50 to ⫹50 pA for 20 msec, and the average
change in cone voltage (bottom) and bipolar current (top) was measured.
The voltage change in the cone was essentially identical in the presence
(thin trace) and absence (thick trace) of the contrast stimulus. The bipolar
response to depolarization of the cone decreased in the presence of the
contrast stimulus, indicating a contrast-dependent change in the gain of
signal transfer. Mean light intensity, 18,800 photons ␮m ⫺2 sec ⫺1 using
640 nm LED; bandwidth, 0 –30 Hz. Bipolar holding potential, ⫺60 mV. B,
Measurements from a current-clamped rod and voltage-clamped OFF
bipolar cell. The bipolar response to stepping the rod holding current
from ⫺50 to ⫹50 pA decreased in the presence of a 25% contrast light
stimulus, indicating a change in the gain of signal transfer. Mean light
intensity, 22 photons ␮m ⫺2 sec ⫺1 using 470 nm LED; bandwidth, 0 –10
Hz. Bipolar holding potential, ⫺60 mV. Perforated-patch recordings.
trast, suggesting that contrast affects the gain of signal transfer
from photoreceptors to bipolar cells. Simultaneous recordings
from photoreceptors and bipolar cells provided direct evidence
for this conclusion by bypassing the phototransduction process
and measuring the gain of signal transfer directly.
The gain of signal transfer was measured by injecting a depolarizing current pulse into a photoreceptor and measuring the
resulting postsynaptic response in a bipolar cell. This experiment
was repeated in the presence and absence of a 25% contrast light
input, and the gain of signal transfer was compared in the two
conditions. No attempt was made to disrupt gap junctions, so the
bipolar response represents changes in transmitter release from a
collection of electrically coupled photoreceptors (Schwartz, 1976;
Attwell et al., 1984). A similar spread of signals among coupled
photoreceptors occurs under normal conditions in the retina.
Figure 4 A shows results from a cone–ON bipolar pair in which
the cone was current clamped and the bipolar was voltage
clamped. Throughout the experiment, the slice was exposed to
bright 640 nm light. Changing the holding current of the cone
from ⫺50 to ⫹50 pA for 20 msec depolarized the cone and
produced a postsynaptic response in the bipolar cell. Sets of 20
such current pulses delivered in the presence and absence of a
25% contrast light input were interleaved. The bottom panel of
Figure 4 A shows average voltage changes in the cone in response
to the current pulse. Responses in the presence and absence of
the contrast stimulus are superimposed. Neither the mean cone
voltage nor the voltage change produced by the current pulse was
affected by the contrast signal. The top panel of Figure 4 A shows
the response of the bipolar to current injected into the cone. The
Rieke • Temporal Contrast Adaptation in Bipolar Cells
bipolar response was smaller in the presence of the contrast signal
than in its absence, indicating a contrast-dependent change in the
gain of signal transfer.
Figure 4 B shows results from a similar experiment on a rod–
OFF bipolar pair. In this case, the experiment was performed in
the presence of 470 nm light, which produced responses in rods
but was too dim to elicit responses in cones. The bottom panel of
Figure 4 B shows the average voltage response in the rod when the
holding current was changed from ⫺50 to ⫹50 pA for 100 msec.
Responses in the presence and absence of a 25% contrast light
input are superimposed. Again, the contrast stimulus had little or
no effect on either the mean rod voltage or the voltage response
to the current pulse. The top panel in Figure 4 B shows the bipolar
response to current injected into the rod. As for the cone–bipolar
pair, the bipolar response was smaller in the presence of the
contrast signal. Contrast also appeared to speed the kinetics of
signal transfer from the rod to the OFF bipolar, as observed for the
light responses of OFF bipolars (see Fig. 6).
A similar contrast dependence of the gain of signal transfer was
observed in four cone–bipolar and six rod–bipolar pairs. The
contrast dependence of signal transfer could be produced by
either presynaptic or postsynaptic mechanisms. Because horizontal cells and bipolar cells both receive direct input from photoreceptors, the lack of contrast adaptation in horizontal cells (Fig.
3B) suggests that the changes in signal transfer are not a property
of presynaptic mechanisms in the photoreceptor synaptic terminal but are generated postsynaptically in the bipolar cell. Additional evidence for this conclusion is provided by the experiments
of Figure 10 described below.
J. Neurosci., December 1, 2001, 21(23):9445–9454 9449
Figure 5. Kinetics of onset and offset of contrast adaptation. An OFF
bipolar cell was voltage clamped while the contrast of the light input was
switched between 10 and 30% every 10 sec. The time-dependent variance
was computed from 21 repetitions of this stimulus. The smooth curves fit
to the variance are single exponentials, with time constants of 2.1 sec (fit
between 0 and 10 sec) and 6.2 sec (fit between 10 and 20 sec). Mean light
intensity, 18,200 photons ␮m ⫺2 sec ⫺1 using 640 nm LED; bandwidth,
0 –30 Hz. The bipolar holding potential was ⫺60 mV, resulting in a ⫺70
pA average current. Perforated-patch recording.
Properties of contrast adaptation in bipolar cells
Time course of onset and offset
The onset and offset of contrast adaptation in the retina occur on
several time scales (Victor, 1987; Sakai et al., 1995; Smirnakis et
al., 1997; Kim and Rieke, 2001). For example, the onset of
contrast adaptation in salamander retinal ganglion cells includes
components with ⬃1 and ⬃10 sec time constants (Kim and Rieke,
2001). To determine the kinetics of the onset and offset of
contrast adaptation in bipolar cells, the contrast was switched
between 10 and 30% periodically, and the time-dependent variance of the resulting bipolar response was measured. Figure 5
shows the variance in the current response of a voltage-clamped
OFF bipolar cell for contrast switches every 10 sec. The changes in
the variance after increases (t ⫽ 0) and decreases (t ⫽ 10 sec) in
contrast were fit by single exponentials (Fig. 5, smooth curves).
The time constants for the onset and offset of contrast adaptation
in this cell were 2.1 and 6.2 sec. In nine cells, the onset of contrast
adaptation had a time constant of 1.8 ⫾ 0.3 sec (mean ⫾ SEM),
and the offset had a time constant of 4.7 ⫾ 0.8 sec. The input
currents to ganglion cells exhibited a similar asymmetry between
the kinetics of the onset and offset of contrast adaptation (Kim
and Rieke, 2001). Bipolar cells, however, showed no evidence for
a slower temporal component after an increase in contrast like
that seen in ganglion cells. Thus, bipolar cells contribute to the
fast-onset component of contrast adaptation observed in the
ganglion cells.
ON
and
OFF
bipolars adapt differently to contrast
Contrast adaptation differed in ON and OFF bipolar cells. Although
contrast affected the amplitude of the light responses in both
types of bipolar cell, the effect of contrast on the response kinetics
was pronounced in OFF bipolars and small or absent in ON bipo-
Figure 6. Contrast adaptation differed in ON and OFF bipolar cells.
Contrast adaptation was measured for 10 and 30% contrast light inputs
using the static nonlinearity model as in Figures 1 and 3. Linear filters
measuring the amplitude and kinetics of the current response of a cell are
shown in A for a voltage-clamped OFF bipolar and in B for a voltageclamped ON bipolar. Insets show responses to 1 sec light steps. The holding
potential in both cases was ⫺60 mV, resulting in a current of ⫺60 pA in
the OFF bipolar and ⫺90 pA in the ON bipolar. Mean light intensity, 17,800
photons ␮m ⫺2 sec ⫺1 in A and 18,200 photons ␮m ⫺2 sec ⫺1 in B, both
using 640 nm LED. C, Collected measures of the amplitude of the filter
at 30% contrast relative to that at 10% contrast for 17 OFF bipolars and 25
ON bipolars. Error bars are SEM. D, Collected measures of the time-topeak of the filter at 30% contrast relative to that at 10% contrast.
Perforated-patch recordings.
lars. ON and OFF bipolars were distinguished based on their
responses to 1 sec light increments. Under voltage clamp, a light
increment generated an outward current in an OFF bipolar (Fig.
6 A, inset) and an inward current in an ON bipolar (Fig. 6 B, inset).
No attempt was made to divide ON and OFF bipolars into subtypes
(Burkhardt and Fahey, 1998; Wu et al., 2000).
Contrast adaptation was measured by presenting 10 and 30%
9450 J. Neurosci., December 1, 2001, 21(23):9445–9454
Rieke • Temporal Contrast Adaptation in Bipolar Cells
contrast inputs and characterizing the amplitude and kinetics of
the light response of a cell using the static nonlinearity model.
Figure 6 shows linear filters for an OFF bipolar (Fig. 6 A) and an ON
bipolar (Fig. 6 B), both measured under voltage clamp. The static
nonlinearities did not change with contrast (data not shown), and
thus contrast adaptation was restricted to changes in the linear
filters. In the OFF bipolar, increasing the contrast from 10 to 30%
decreased the amplitude and the time-to-peak of the filter. In the
ON bipolar, increasing the contrast from 10 to 30% produced a
clear change in amplitude but little or no change in the time-topeak. Figure 6C summarizes measurements of the amplitude of
the filter at high contrast relative to that at low contrast for 17 OFF
bipolars and 25 ON bipolars, all measured under voltage clamp.
Contrast had a slightly larger effect on the amplitude of the light
responses of OFF bipolars than ON bipolars. Figure 6 D summarizes
measurements of the time-to-peak of the linear filter at high
contrast relative to that at low contrast. The change in response
kinetics was clear in OFF bipolars and small or absent in ON
bipolars. A similar asymmetry between the effect of contrast on
the responses of ON and OFF bipolars was observed in currentclamp recordings. This asymmetry contributes to an ON – OFF
asymmetry in the light responses of salamander retinal ganglion
cells (Chander and Chichilnisky, 1999; Kim and Rieke, 2001) (see
Discussion).
Contrast adaptation affects rod- and cone-mediated responses
Contrast affected the amplitude and kinetics of the bipolar responses over a wide range of light intensities. Thus, contrast
adaptation acted on signals from both rod and cone photoreceptors. Rod-dominated responses were studied using 470 nm light at
mean intensities of 4 – 40 photons ␮m ⫺2 sec ⫺1, too dim to produce responses in the cones. Cone-dominated responses were
studied using 640 nm light at mean intensities of 3,000 – 80,000
photons ␮m ⫺2 sec ⫺1, light levels sufficient to saturate the rods.
Contrast adaptation was studied by delivering 10 and 30% light
inputs and measuring steady-state sensitivity using the static
nonlinearity model. Figure 7 shows linear filters measured for
rod- (Fig. 7A) and cone- (Fig. 7B) dominated responses in a
voltage-clamped OFF bipolar cell. The corresponding static nonlinearities overlapped and hence did not contribute to contrast
adaptation (data not shown). Rod-mediated responses were
slower than cone-mediated responses, as expected from the
slower kinetics of the photoreceptor responses themselves. However, increasing the contrast of the light input from 10 to 30%
decreased the amplitude and the time-to-peak of the filter for
both rod- and cone-mediated signals. Contrast affected the sensitivity of the bipolar cell responses for mean light levels as low as
4 photons ␮m ⫺2 sec ⫺1 (three cells) and as high as 80,000 photons
␮m ⫺2 sec ⫺1 (six cells). This indicates that contrast adaptation in
photoreceptor–bipolar signal transfer is a general property of how
signals are processed by the retinal circuitry.
Mechanism of contrast adaptation in bipolar cells
The effect of contrast on the sensitivity of bipolar cells and lack of
an effect on the sensitivities of photoreceptors and horizontal
cells (Fig. 3) indicates that contrast adaptation is mediated after
signals are transferred to the bipolar cell. The experiments described below tested several possible mechanisms: (1) voltageactivated conductances in the bipolar soma (Mao et al., 1998); (2)
amacrine feedback to the bipolar synaptic terminal (Maguire et
al., 1989); (3) horizontal cell input to the bipolar dendrites
Figure 7. Contrast affected both rod- and cone-mediated responses. A,
Linear filters for a voltage-clamped OFF bipolar cell for 10 and 30%
contrast light inputs using 470 nm light at a mean intensity of 24 photons
␮m ⫺2 sec ⫺1 and a bandwidth of 0 –10 Hz. The wavelength and low mean
intensity favored responses of rods over those of cones. B, Linear filters
for the same cell for 10 and 30% contrast light inputs using 640 nm light
at a mean intensity of 18,800 photons ␮m ⫺2 sec ⫺1 and a bandwidth of
0 –30 Hz. These conditions favored the responses of L cones over those of
rods. The holding potential was ⫺60 mV, resulting in a current of ⫺40
pA. Perforated-patch recording.
(Mangel, 1991); and (4) Ca 2⫹-dependent mechanisms in the
bipolar dendrites (Shiells and Falk, 1999; Nawy, 2000).
Voltage-activated conductances in bipolar soma make a
minimal contribution
If voltage-activated conductances in the bipolar soma make a
substantial contribution to contrast adaptation, the effect of contrast on the light response of a bipolar should differ when the
bipolar voltage is free to change or held constant. The extent of
contrast adaptation under current and voltage clamp was measured using the static nonlinearity model as in Figures 1 and 3.
Figure 8 A shows linear filters at 10 and 30% contrast for a
voltage-clamped OFF bipolar cell. Contrast affected the amplitude
and kinetics of the filter. Figure 8 B shows linear filters for
current-clamp responses from the same cell. Contrast again affected the amplitude and kinetics of the filter, and the magnitude
of these effects was similar to that observed under voltage clamp.
The extent of contrast adaptation with the membrane voltage
clamped or free to change was compared in seven OFF bipolars
and five ON bipolars; collected results are shown in Figure 8, C
and D. Figure 8C plots the change in the amplitude of the linear
filter measured under voltage clamp against that measured under
current clamp, with each point representing measurements from a
Rieke • Temporal Contrast Adaptation in Bipolar Cells
J. Neurosci., December 1, 2001, 21(23):9445–9454 9451
Figure 8. Contrast adaptation was similar under current and voltage
clamp. A, Linear filters for a voltage-clamped OFF bipolar cell for 10 and
30% contrast light inputs. Holding potential was ⫺60 mV, resulting in a
current of ⫺90 pA. B, Linear filters for the same cell from current-clamp
responses. Holding current was ⫺50 pA, resulting in a voltage of ⫺48 mV.
Mean light intensity, 16,100 photons ␮m ⫺2 sec ⫺1 using 640 nm LED. C,
Collected results on the change in amplitude of the filter from voltageclamp ( y-axis) and current-clamp (x-axis) responses. Each point represents one cell. The line has a slope of 1 and hence is the expectation of
contrast adaptation was the same under current and voltage clamp. D,
Collected results on the change in time-to-peak of the filter. Perforatedpatch recording.
single cell as in Figure 8, A and B. Figure 8 D compares the
change in time-to-peak of the filters measured under voltage and
current clamp. In each case, the points cluster near the line of
identity, indicating that the effect of contrast on the amplitude
and kinetics of the light responses of bipolar cells was similar
under current and voltage clamp. These experiments show that
voltage-activated conductances in the bipolar soma make little or
no contribution to contrast adaptation.
Contrast adaptation persists without amacrine feedback
To test whether the effect of contrast could be attributable to
amacrine feedback to the bipolar synaptic terminal, contrast
adaptation was measured with the amacrine feedback working
normally and with it suppressed. Amacrine feedback was suppressed with picrotoxin and strychnine, inhibitors of the GABA
(Maguire et al., 1989) and glycine (Maple and Wu, 1998; Cook et
al., 2000) receptors on the bipolar synaptic terminal. A substantial
increase in the amplitude of the light responses of amacrine and
ganglion cells confirmed that that picrotoxin and strychnine were
effective in altering inhibition from amacrine cells (data not
shown).
The effect of contrast on the amplitude and kinetics of the light
response of a bipolar persisted in the presence of picrotoxin and
strychnine. Figure 9, A and B, compares the extent of contrast
adaptation in a voltage-clamped OFF bipolar cell superfused with
normal Ringer’s solution (Fig. 9A) or with Ringer’s solution
containing 150 ␮M picrotoxin and 5 ␮M strychnine (Fig. 9B).
Picrotoxin and strychnine did not substantially alter the effect of
contrast. Results from 13 bipolars in which contrast adaptation
was measured with and without amacrine feedback are summarized in Figure 9C, which plots the effect of contrast on the
amplitude of the response of a cell in picrotoxin and strychnine
( y-axis) against that in Ringer’s solution (x-axis). Each point
represents measurements on a single cell. The points cluster
Figure 9. Amacrine and horizontal cells contributed little to contrast
adaptation. A, Linear filters for a voltage-clamped OFF bipolar cell superfused in normal Ringer’s solution for light inputs of 10 and 30% contrast.
B, Linear filters for the same cell as in A superfused in Ringer’s solution
containing 150 ␮M picrotoxin and 5 ␮M strychnine. Holding potential was
⫺60 mV, resulting in a current of ⫺60 pA. C, Collected results on the
amplitude of the filter at 30% contrast relative to that at 10% contrast for
13 cells tested in both normal Ringer’s solution and Ringer’s solution
containing picrotoxin and strychnine. Each point represents one cell as in
A and B. The line has a slope of 1 and thus represents the expectation if
picrotoxin and strychnine had no effect on contrast adaptation. D, Linear
filters for a voltage-clamped OFF bipolar in normal Ringer’s solution. E,
Linear filters for the same cell as in D superfused in Ringer’s solution
containing 5 ␮M bicuculline. Holding potential was ⫺60 mV, resulting in
a current of ⫺30 pA. F, Collected results on amplitude of the filter at 30%
contrast relative to that at 10% contrast for seven cells tested in both
normal Ringer’s solution and Ringer’s solution containing bicuculline. All
were perforated-patch recordings. Mean light intensity, 17,200 photons
␮m ⫺2 sec ⫺1 using 640 nm LED; bandwidth, 0 –30 Hz.
around the line of identity, indicating that contrast adaptation was
similar in the two cases. The average amplitude of the filter at
high contrast relative to that at low contrast was 0.80 ⫾ 0.02
(mean ⫾ SEM) in normal Ringer’s solution and 0.82 ⫾ 0.02 with
amacrine feedback suppressed. Thus, contrast adaptation was
affected little when amacrine feedback to the bipolar terminal was
suppressed, and most or all of the adaptation was attributable to
other mechanisms.
Contrast adaptation persists when horizontal inputs to bipolars
are suppressed
To test whether the effect of contrast could be attributable to
horizontal cell input to the bipolar dendrites, contrast adaptation
was compared before and after suppressing the horizontal–bipolar synapse with bicuculline, an inhibitor of GABA receptors on
the bipolar dendrites. The effect of contrast was essentially unchanged by suppression of horizontal input to bipolars.
Figure 9, D and E, compares the extent of contrast adaptation
Rieke • Temporal Contrast Adaptation in Bipolar Cells
9452 J. Neurosci., December 1, 2001, 21(23):9445–9454
of a voltage-clamped OFF bipolar cell superfused with normal
Ringer’s solution (Fig. 9D) or with Ringer’s solution containing 5
␮M bicuculline (Fig. 9E). Contrast adaptation was similar in the
two conditions. Figure 9F collects results from seven such experiments, plotting the effect of contrast on the amplitude of the
response of a cell in bicuculline ( y-axis) against that in Ringer’s
solution (x-axis). Contrast adaptation was essentially unchanged
in the presence of bicuculline. The average amplitude of the filter
at high contrast relative to that at low contrast in these seven cells
was 0.80 ⫾ 0.05 (mean ⫾ SEM) in both Ringer’s solution and
bicuculline. Thus, horizontal cell input to bipolars does not make
a substantial contribution to contrast adaptation.
Ca 2⫹ buffers eliminate contrast adaptation in
OFF
bipolars
The experiments of Figure 9 show that contrast adaptation persists when a bipolar cell is voltage clamped and amacrine feedback to the bipolar terminal is suppressed. Under these conditions, the voltage in the axon terminal should not change, and
thus conductances in the axon terminal do not contribute significantly to contrast adaptation. The similarity of contrast adaptation under current and voltage clamp (Fig. 8) indicates that
conductances in the soma do not make significant contributions.
Thus, Figures 8 and 9 indicate that most of the contrast adaptation in the light response of a bipolar is generated in its dendrites.
Several studies have identified Ca 2⫹-dependent gain controls
in the dendrites of ON bipolar cells (Shiells and Falk, 1999; Nawy,
2000). To test whether such a mechanism might contribute to
contrast adaptation, changes in Ca 2⫹ were suppressed by dialyzing a bipolar cell with a high concentration of Ca 2⫹ buffer and
measuring the consequences for contrast adaptation. The Ca 2⫹
buffer and total Ca 2⫹ in the dialyzing solution were increased by
the same factor to keep the free Ca 2⫹ concentration constant.
HEDTA and diBromoBAPTA (Br2BAPTA) were used as Ca 2⫹
buffers because they have a relatively low affinity for Ca 2⫹ and
thus are not likely to become fully Ca 2⫹ bound.
Increasing the Ca 2⫹ buffer concentration eliminated contrast
adaptation in OFF, but not ON, bipolars. The effect of contrast on
the gain and kinetics of the light response of a cell was measured
using the static nonlinearity model (Fig. 1). Figure 10 A shows
linear filters at 10 and 30% contrast for a voltage-clamped OFF
bipolar dialyzed with a solution containing 1 mM HEDTA. As for
perforated-patch recordings, contrast affected the amplitude and
kinetics of the filter. Figure 10 B shows filters for a voltageclamped OFF bipolar dialyzed with a solution containing 10 mM
HEDTA. In this case, contrast had little or no effect on the
amplitude or kinetics of the filter. Results from OFF bipolars
dialyzed with high and low concentrations of Ca 2⫹ buffers are
summarized in Figure 10C and compared with the extent of
contrast adaptation in cells with native Ca 2⫹ buffers (perforatedpatch recordings). All cells in which Ca 2⫹ changes were suppressed with high Ca 2⫹ buffer concentrations showed essentially
no contrast adaptation.
Contrast adaptation in ON bipolars had little or no dependence
on the Ca 2⫹ buffer concentration. Figure 10 D shows linear filters
at 10 and 30% contrast for a voltage-clamped ON bipolar dialyzed
with a solution containing 1 mM HEDTA. Figure 10 E shows
filters for a voltage-clamped ON bipolar dialyzed with a solution
containing 10 mM HEDTA. In both cases, the sensitivity of the
light response of a cell decreased with increases in contrast.
Figure 10 F collects results from ON bipolars dialyzed with high
and low concentrations of Ca 2⫹ buffer and with native buffers
intact. Contrast adaptation was similar in all three conditions.
Figure 10. High concentrations of Ca 2⫹ buffers suppress contrast adaptation in OFF, but not ON, bipolars. Contrast adaptation was compared in
whole-cell recordings from bipolar cells dialyzed with internal solutions
containing either 1 or 10 mM of the Ca 2⫹ buffer HEDTA. The total Ca 2⫹
in the internal solutions was changed along with the Ca 2⫹ buffer concentration to keep the free Ca 2⫹ constant. A, Linear filters for 10 and 30%
contrast light inputs for a voltage-clamped OFF bipolar dialyzed with 1 mM
HEDTA. Holding potential was ⫺60 mV, resulting in a current of ⫺50
pA. B, Filters for a voltage-clamped OFF bipolar dialyzed with 10 mM
HEDTA. Holding potential was ⫺60 mV, resulting in a current of ⫺40
pA. C, Collected results from OFF cells on the effect of contrast on the
filter amplitude for perforated-patch recordings (native) and whole-cell
recordings from cells dialyzed with 1 and 10 mM HEDTA. All were
voltage-clamp recordings. D, Filters for a voltage-clamped ON bipolar
dialyzed with 1 mM HEDTA. Holding potential was ⫺60 mV, resulting in
a current of ⫺70 pA. E, Filters for a voltage-clamped ON bipolar dialyzed
with 10 mM HEDTA. Holding potential was ⫺60 mV, resulting in a
current of ⫺40 pA. F, Collected results from ON cells. Mean light intensity, 18,500 photons ␮m ⫺2 sec ⫺1 using 640 nm LED; bandwidth, 0 –30 Hz.
Contrast adaptation also persisted in voltage-clamped ON bipolar
cells dialyzed with a solution containing 5 mM Br2BAPTA (data
not shown). In eight cells dialyzed with Br2BAPTA, the amplitude of the linear filter for 30% contrast inputs relative to 10%
contrast inputs was 0.81 ⫾ 0.04 (mean ⫾ SEM), again similar to
the extent of contrast adaptation with the native Ca 2⫹ buffers
intact.
The results summarized in Figure 10 indicate that Ca 2⫹dependent mechanisms in the bipolar dendrites contribute to
contrast adaptation in OFF, but not ON, bipolars. This difference
may help explain why OFF bipolar cells adapt more strongly to
contrast changes than ON bipolars (Fig. 6).
DISCUSSION
The experiments described here lead to three conclusions about
contrast adaptation in salamander bipolar cells: (1) bipolar cells,
but not horizontal cells or photoreceptors, adapt to temporal
contrast; (2) contrast adaptation in the bipolars has a relatively
Rieke • Temporal Contrast Adaptation in Bipolar Cells
fast onset and offset; and (3) the functional properties of contrast
adaptation in ON and OFF bipolars differ. The properties of contrast adaptation in salamander bipolar cells are discussed below
and compared with adaptation in retinal ganglion cells.
Contrast gain and contrast adaptation
Contrast adaptation in signal transfer from photoreceptors to
bipolars serves an important role in protecting against saturation.
For contrast steps about a steady light level, the contrast gain of
salamander bipolar cells is 5–10 times higher than that of cones
(Burkhardt and Fahey, 1998) (Figs. 2, 3). Thus, without adaptation, fluctuating light inputs with a contrast of 5–10% would lead
to significant saturation of the bipolar responses; such saturation
would compromise encoding of visual inputs. Contrast adaptation
may be a general feature of signal processing in bipolar cells. In
rabbit, altering the contrast in the surround of the receptive field
of a ganglion cell does not affect the gain of the receptive field
center, suggesting that mammalian bipolar cells, which provide
the receptive field center, also adapt to contrast (Brown and
Masland, 2001).
Time course of onset and offset in bipolar and
ganglion cells
After an increase in contrast, the onset of adaptation in the
currents measured at the ganglion cell soma included fast (1–2
sec) and slow (10 –20 sec) components (Kim and Rieke, 2001),
suggesting that at least two distinct mechanisms contribute. The
fast component in the ganglion cell currents accounted for a
20 –30% reduction in the sensitivity when the contrast was increased by a factor of three (Kim and Rieke, 2001). In bipolar
cells, the onset of contrast adaptation was restricted to a fast (1–2
sec) component. A threefold increase in contrast reduced the
bipolar sensitivity by 20 –25%, similar to the reduction in the
sensitivity of a ganglion cell attributable to the fast-onset component of contrast adaptation. Thus, adaptation in the bipolar cells
can account for most or all of the fast-onset contrast adaptation
seen in the currents at the ganglion cell soma. Bipolar cells did
not show a substantial slow component of contrast adaptation,
and hence this component must originate at a later stage in
retinal processing.
The different temporal components of contrast adaptation
likely play different functional roles in retinal signal processing.
The slow onset form of contrast adaptation observed in the
responses of retinal ganglion cells (Smirnakis et al., 1997) is well
suited to dynamically adjust visual sensitivity to match the temporal and spatial structure of the light inputs. The fast-onset
component of contrast adaptation seen in the bipolar cells and
ganglion cells is likely to shape responses to single visual objects,
e.g., objects moving through the receptive field of a cell (Berry et
al., 1999). The fast-onset component of contrast adaptation in the
output spike trains of a ganglion cell contains approximately
equal contributions from adaptation in the bipolar cells and
adaptation in spike generation in the ganglion cell itself (Kim and
Rieke, 2001).
The onset and offset of contrast adaptation follow different
time courses in both bipolars (Fig. 5) and ganglion cells (Smirnakis et al., 1997; Brown and Masland, 2001), with the offset of
adaptation proceeding more slowly than the onset. The asymmetry between the time course of the onset and offset is in agreement with theoretical arguments about the ease with which increases and decreases in contrast can be detected from the
response of a cell (DeWeese and Zador, 1998).
J. Neurosci., December 1, 2001, 21(23):9445–9454 9453
Functional and mechanistic differences between
and OFF bipolars
ON
The functional properties of contrast adaptation differed for ON
and OFF bipolar cells (Fig. 6). Increases in contrast had a similar
effect on the amplitude of the light responses in ON and OFF cells.
Changes in contrast, however, had a much more pronounced
effect on the kinetics of the response of OFF bipolars than ON
bipolars. In salamander retinal ganglion cells, changes in contrast
had a greater effect on both the amplitude and kinetics of the light
response in OFF cells than ON cells (Chander and Chichilnisky,
1999, 2001; Kim and Rieke, 2001). Thus, some but not all of the
ON – OFF asymmetry in the ganglion cells can be accounted for by
the asymmetry in the bipolars.
In addition to the difference in functional properties, the mechanisms mediating contrast adaptation in ON and OFF bipolars
differed (Fig. 10). In both cell types, contrast adaptation was
mediated by mechanisms in the dendrites. In OFF bipolars, suppressing changes in Ca 2⫹ eliminated contrast adaptation, indicating that a Ca 2⫹-dependent gain control in the dendrites was
responsible. In ON bipolars, suppressing Ca 2⫹ changes had little
or no effect on contrast adaptation. Adaptation in ON bipolars
could be mediated by desensitization of glutamate receptors or
regulation of the second-messenger cascade coupling the receptors to channels (Nawy, 1999).
Mean and contrast adaptation in the retina
The output signals of retinal ganglion cells adapt to both the
mean light intensity (for review, see Walraven et al., 1990) and the
temporal contrast (for review, see Shapley, 1997; Meister and
Berry, 1999). The extent to which mean and contrast adaptation
operate independently has an important bearing on how vision
adjusts to changes in the statistics of the light inputs.
At high light levels, the mean and contrast of a visual scene are
primarily independent, with the mean determined primarily by
the illuminating light source and the contrast by the distribution
of reflectances in the scene. At low light levels, the mean and
contrast of the light inputs cannot change independently because
of quantal fluctuations in the incident photons. Indeed, the form
of adaptation operating at the lowest light intensity is mediated by
mechanisms in the retinal circuitry controlled by quantal fluctuations in the light input (Donner et al., 1990), likely the same
mechanisms causing contrast adaptation at higher light levels.
Several observations suggest that adaptation to the mean light
intensity and the fluctuations about the mean are primarily independent in the outer retina. First, photoreceptors contribute to
adaptation to the mean light level (for review, see Walraven et al.,
1990; Koutalos and Yau, 1996) but not to contrast adaptation
(Fig. 3) (Sakai et al., 1995; Smirnakis et al., 1997). Second,
Ca 2⫹-dependent mechanisms in the dendrites of ON bipolar cells
contribute to mean but not contrast adaptation (Shiells and Falk,
1999) (Fig. 10). Third, results described here suggest that signal
transfer from photoreceptors to bipolars can be described as a
contrast-dependent linear filter in the bipolar dendrites followed
by a static nonlinearity (Fig. 3). Consistent with this description,
the static nonlinearity was much less pronounced in voltageclamp experiments than current-clamp experiments and thus
appeared to be dominated by voltage-dependent conductances in
the bipolar soma. This indicates that contrast adaptation must be
produced by a change in the fluctuations of the bipolar response
rather than a change in the mean response.
9454 J. Neurosci., December 1, 2001, 21(23):9445–9454
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