J Neurophysiol 117: 4 –17, 2017.
First published October 5, 2016; doi:10.1152/jn.00289.2016.

RESEARCH ARTICLE

Sensory Processing

Whisker row deprivation affects the flow of sensory information through rat
barrel cortex
Vincent Jacob,*1 Akinori Mitani,*2,3 Taro Toyoizumi,*2 and X Kevin Fox*1
1

School of Biosciences, Cardiff University, Cardiff, United Kingdom; 2RIKEN Brain Science Institute, Wako, Saitama, Japan;
and 3Department of Neurosciences, University of California, San Diego, La Jolla, California
Submitted 8 April 2016; accepted in final form 1 October 2016

NEW & NOTEWORTHY Sensory cortical plasticity is usuallyquantified by changes in evoked firing rate. In this study we quantified
plasticity by changes in sensory detection performance using Chernoff
information and receiver operating characteristic analysis. We foundthat whisker deprivation causes a change in information flow within
the cortical layers and that layer 5 regular-spiking cells, despite
showing only a small potentiation of short-latency input, show thegreatest increase in information content for the spared input partly bydecreasing their spontaneous activity.
cortical circuit; conductance; cortical column; plasticity; vibrissa

dynamically reshapes cortical receptive
fields. Subregions of the receptive field can be strengthened or
weakened by altering the balance of sensory drive between
competing inputs. In layers 2/3 (L2/3), the nature of receptive

SENSORY EXPERIENCE* V. Jacob and A. Mitani contributed equally to this work. T. Toyoizumi andK. Fox are co-senior authors.
Address for reprint requests and other correspondence: K. Fox, School of
Biosciences, Cardiff Univ., Museum Ave., Cardiff CF10 3AX, UK (e-mail:foxkd@cardiff.ac.uk).
4field plasticity is known to vary with the type of sensory
modification set by the experimenters, but for any given patternof deprivation, the plasticity is relatively uniform in effectacross neurons (Feldman and Brecht 2005; Wallace and Fox1999). In contrast, we recently found that a row-deprivation
pattern can cause nonuniform receptive field plasticity in subtypes of layer 5 (L5) pyramidal cells (Jacob et al. 2012). The
two main types of pyramidal cells in cortical layer L5 are
known as thick tufted or intrinsically bursting (IB) cells andthin slender or regular-spiking (RS) cells (Chagnac-Amitai etal. 1990; Connors and Gutnick 1990; McCormick et al. 1985).
In deprived columns of barrel cortex, spared whisker inputs
were potentiated in IB cells together with little depression ofdeprived inputs, whereas RS cell responses to deprived whiskers were depressed without potentiation of spared input (Jacob et al. 2012).
What mechanisms might be responsible for the different
reactions of different cell types to the same deprivation pattern? At the cellular level, these include different capacities
between cells for particular synaptic plasticity processes suchas long-term potentiation (LTP), long-term depression (LTD),and homeostatic plasticity; at the circuit level, these include thedynamic interaction between cells in different layers of thecortical columns, the relative strength of cortical vs. thalamic
input differences, and changes in the balance between excitatory and inhibitory inputs. A previous study in mouse barrel
cortex has provided evidence Hebbian and homeostatic mechanisms are recruited to different degrees in L5RS and L5IB
cells (Greenhill et al. 2015). In this study we have concentrated
on the differences that might arise at the circuit level.
To understand the information flow between layers, werecorded intracellularly from all layers and compared spontaneous activity and receptive fields using both conventional
measures of activity (subthreshold inputs and suprathresholdoutputs) and analysis of Chernoff information induced bywhisker stimulation. We also analyzed response latencies tojudge the relative dominance of rapid thalamic vs. slower
intracortical inputs after plasticity. Finally, in a separate set ofexperiments, we measured synaptic conductance of evokedpostsynaptic potentials (PSPs) in RS and IB cells as a first step
toward understanding whether the excitatory inhibitory balancemight be responsible for differing expression of potentiationand depression in IB and RS cells, respectively. Although
L5RS cell responses did not potentiate above the baseline value

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Jacob V, Mitani A, Toyoizumi T, Fox K. Whisker row deprivation affects the flow of sensory information through rat barrel cortex.
J Neurophysiol 117: 4 –17, 2017. First published October 5, 2016;
doi:10.1152/jn.00289.2016.—Whisker trimming causes substantial
reorganization of neuronal response properties in barrel cortex. However, little is known about experience-dependent rerouting of sensory
processing following sensory deprivation. To address this, we performed in vivo intracellular recordings from layers 2/3 (L2/3), layer 4(L4), layer 5 regular-spiking (L5RS), and L5 intrinsically bursting(L5IB) neurons and measured their multiwhisker receptive field at thelevel of spiking activity, membrane potential, and synaptic conductance before and after sensory deprivation. We used Chernoff information to quantify the “sensory information” contained in the firing
patterns of cells in response to spared and deprived whisker stimulation. In the control condition, information for flanking-row andsame-row whiskers decreased in the order L4, L2/3, L5IB, L5RS.
However, after whisker-row deprivation, spared flanking-row whisker
information was reordered to L4, L5RS, L5IB, L2/3. Sensory information from the trimmed whiskers was reduced and delayed in L2/3
and L5IB neurons, whereas sensory information from spared whiskers
was increased and advanced in L4 and L5RS neurons. Sensory
information from spared whiskers was increased in L5IB neurons
without a latency change. L5RS cells exhibited the largest changes insensory information content through an atypical plasticity combining
a significant decrease in spontaneous activity and an increase in ashort-latency excitatory conductance.

PLASTICITY OF CORTICAL INFORMATION FLOW

(as reported by Jacob et al. 2012), they were specifically foundto convey increased information on spared whisker stimulation
due to the combination of lower spontaneous activity andpotentiation of a fast excitatory component.
METHODS

thesia. Biocytin staining of L5 cells was revealed in coronal sections(300 ␮m thick) using Vectastain ABC kits (Vector Laboratories,
Peterborough, UK). The morphology of a subset of recorded cells wasrecovered and used to establish a correlation between somatic positionand electrode depth from the surface of the saline solution above thepia. The border between L2/3 and L4 was found to be located at a
depth of 575 ␮m, the border between L4 and L5 was located at a depthof 950 ␮m, and the border between L5 and L6 was located at a depthof 1,400 ␮m. The cells used for morphological characterization
included part of the cells whose receptive fields were recorded plus anadditional sample. We did not have a sufficient sample to classify
receptive fields according to cell morphology. Instead, we usedphysiological criteria. A number of methods are available to classify
L5 cells into IB and RS populations, but none unambiguously classify
all cells. Nevertheless, the classification bias we encountered is likely
to be marginal because we observed that 88% of the cells wereclassified into the same categories with the use of two distinct
methods: these were the original method based on evoked firing(Connors and Gutnick 1982) and a more recent quantitative method
based on spontaneous activity (Nowak et al. 2003). In the present
study we decided to use the original method: L5 cells were identified
as IB cells if they responded to current injection at least once witha characteristic burst shape, comprising high-frequency action
potential decreasing in size, superimposed on a slow depolarization(“calcium”) event. Cells were identified as RS cells if they responded to increasing amplitude of current injection with regulartrains of spikes. For a detailed discussion on distinguishing IB and
RS cells, see Jacob et al. (2012). In rats. the two L5 cell subtypes
are not strictly confined to sublayers 5a and 5b (Nayaranan et al.
2015), but we still observed that two-thirds of IB cells lay withinlayer 5b. Recordings from fast-spiking neurons were made but notincluded in this data set.
Our histological methods were designed to recover cell morphology. Therefore, we used a functional assay to identify the principal
barrel. At the beginning of every electrode penetration, local fieldpotentials were recorded systematically in L4. The principal whisker
was identified as the whisker evoking the shortest latency, fastest risetime-evoked potential in L4. Intracellular recordings were performed
within the same electrode penetration only if an obvious principal
whisker emerged in the D-row. Septal recording locations are unlikely
with this method because evoked potentials in septal locations tend to
generate similar responses to several whiskers. In a subset of experiments, the angle of the electrode was slightly off normal to a tangent
to the brain surface, and this was taken into account in aiming at the
D-row barrels.
Chernoff information. Chernoff information is an objective way tocharacterize discriminability between two probability distributions.
We measured the “distance” between an evoked firing rate trace f(t)and a baseline firing rate trace g(t) by using the Chernoff information(Chernoff 1952; Cover and Thomas 1991; Kang et al. 2004), assuming that spiking probability in each condition was approximated by aninhomogeneous Poisson processes. This quantity is an upper bound on
the accuracy of an optimal decoder in discriminating whether theobserved spikes are generated from the firing rate trace f(t) or g(t). We
visually inspected the validity of the inhomogeneous Poisson assumption after applying the time-rescaling method (Brown et al. 2002) but
found no clear deviation in most cells, possibly because of the low
spike count under our sparse stimulation protocol. Notably, theChernoff information is meaningful even if the inhomogeneous
Poisson assumption is violated; in this case, this quantity summarizes the accuracy of a simple decoder based on linear summationof spikes instead of an optimal decoder. f(t) was the peristimulus
time histogram (PSTH) after stimulation of a whisker (bin ⫽ 1 ms).
g(t) ⫽g0 was a constant function whose value was the mean firing
rate estimated from 40 to 10 ms before the stimulus onset. The
Chernoff information upper bounds the error in estimating thepresence or absence of the whisker stimulus on the basis of an

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Subjects and whisker deprivation. Experiments were performed at
Cardiff University and were approved under the UK Scientific Procedures Act 1986. Recordings were performed in 37 control and 30
deprived Long-Evans male rats. Animals were lightly anesthetizedwith isoflurane and had the left D-row of whiskers trimmed to length⬍1 mm (same length as the fur hairs) every 24 or 48 h. Whisker
trimming started at postnatal day 32– 45 (P32–P45) and was continued
for 10 days before recording; the trimmed whiskers were kept andglued to the whisker cut end before stimulation. Control animals wererecorded at the same age as deprived animals, but the D-row ofwhiskers were trimmed and glued on the day of recording. For thisreason, recordings from trimmed whiskers were compared with thosefrom control D-row whiskers, whereas the control for the sparedwhiskers were the C- and E-row whiskers.
Surgery and recording procedures. Anesthesia was induced with
isoflurane and maintained with intraperitoneal injection of urethane(1.5 g/kg body wt). Anesthetic depth was monitored by reflex movements, breathing rate, and cortical activity, and if required, additionaldoses of urethane were injected (0.15 g/kg body wt). Body temperature was maintained at 37°C with a thermostatic heating blanket. The
animal was placed in a stereotaxic frame and a 1-mm-diameter
craniotomy performed over the D1-2 barrels. A separate craniotomy
was made caudally away from the barrel field to insert a carbon fiberreference electrode at the cortical surface. Glass micropipettes filledwith 1 M potassium acetate and 2% biocytin (50 –100 M⍀) wereinserted in the brain through a small opening of the dura. Recordings
were performed in current-clamp mode, and the bridge was balanced
manually (Axoclamp 2B). Recordings were excluded from analysis
when the average membrane potential was within 50 mV of the action
potential peak amplitude. Every 2.2 s between stimulation sequences,a short hyperpolarizing current (10 pA, 100 ms) was injected in thecell and the series and membrane resistance were calculated using adouble exponential fit. Data from 32 L5RS cells and 38 L5IB cells
were already included in a previous study with different analysis(Jacob et al. 2012).
Whisker stimulation. Whiskers were deflected with the use of 9
independent computer-controlled piezoelectric actuators (Physik Instrumente, Bedford, UK) arranged in a 3 ⫻ 3 array (Jacob et al. 2012).
The principal whisker and the 8 immediate neighbor whiskers were
trimmed to 12-mm length and inserted 3 mm into short tubes glued
onto the actuator. When the principal whisker was not at the center of
the array in the control animals, the whiskers two rows or twocolumns apart from the principal whisker were excluded from theanalysis. Each element of the stimulator has a very large range of
positional adjustments due to gimbal joints, and the actuators werepositioned and oriented to maintain the whiskers at their initial resting
position and angle unless stimulated. Piezoelectric bender movement
was controlled by a whisker stimulator driver (CED 3901) interfacedwith a data acquisition interface (CED 1401; Cambridge Electronic
Design, Cambridge, UK). The deflection amplitude of each actuator
was calibrated with a laser displacement measurement system (MicroEpsilon, Ortenburg, Germany). Receptive fields were mapped withsparse noise stimuli composed of pseudorandom sequences of ventral/
dorsal deflections at 5 Hz (interpolated with a nonstimulation event).
Five to 125 sequences (mode 50) were considered, depending on thestability of the recording. Each whisker deflection lasted 30 ms (witha 10-ms plateau phase) to avoid oscillations and was 200 ␮m in peak
amplitude (Fig. 2A).
Cell type identification and location. After recordings were complete, animals were perfused with fixative under deep general anes-

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PLASTICITY OF CORTICAL INFORMATION FLOW

observed spike train. In the current context, the Chernoff information is simply approximated by

兵 兺 log关共 f 共t兲⌬兲 共g共t兲⌬兲␣I ⬵ max ⫺
␣

t

⬵max
␣

1⫺␣

⫹ 共 1 ⫺ f 共 t兲 ⌬兲 ␣

共1 ⫺ g共t兲⌬兲1⫺␣兴 其兺t ⌬关␣ f 共t兲 ⫹ 共1 ⫺ ␣兲g共t兲 ⫺ f ␣共t兲g1⫺␣共t兲兴

Gtatal共t兲 ⫽

1
ã共t兲

ь

⫺C

a共 t兲

ã共t兲

ь

E共t兲 ⫽ ṽ0共t兲 ⫹ C

v 0共 t 兲

Gtotal共t兲

Leak conductance (Grest) and reversal potential (Erest) were estimatedby averaging ⫺40 to ⫺10 ms before the stimulus onset.
Evoked excitatory [Gex(t)] and inhibitory conductances [Gin(t)]were estimated by solving the following equation:
Gtotal共t兲 ⫽ Gex共t兲 ⫹ Gin共t兲 ⫹ Grest
E共t兲Gtotal共t兲 ⫽ EexGex共t兲 ⫹ EinGin共t兲 ⫹ ErestGrest
where Eex ⫽ 0 mV and Ein ⫽ ⫺75 mV are excitatory and inhibitory
reversal potential, respectively. Evoked reversal potential (⌬E) was
estimated by subtracting the baseline average Erest from E.
Statistical tests between control and deprived conditions. We
typically recorded one to two cells of a given type per animal.
Whiskers were first categorized in three trimmed whisker classes andsix spared whisker classes by sorting their response level. We thentested the effect of deprivation on deprived and spared whiskers witha two-way ANOVA using the aligned rank transform (ART; Wobbrock et al. 2011) with cells as independent samples (the number ofcells is indicated by nC). With ART, ANOVA can be applied without
making assumptions about the distribution of the data.
In addition, a bootstrap test was applied to all combinations of acell and whisker as independent samples (number of whisker-cell pairis indicated by nWC) for times around the stimulus. The bootstrap test
has the advantage of making no assumption about the distribution ofdata and of being adapted to low sample size. In most cases, thebootstrap method yielded the same level of significance as ARTANOVA. For each group, the quantity of interest was computed fromeach of the 1,000 data sets resampled from the corresponding datagroup, allowing replacement (bootstrap). This provided resampled
differences of the quantity of interest, from which we reconstructed a
distribution of differences between the groups. The P value was thencalculated by assuming the null hypothesis that there is no statisticaldifference between the control and deprived conditions. Hence, aone-tailed P value in this scenario is given by the probability that thisdifference is either positive or negative. The two-tailed P value istwice the smallest one-tailed P value. The difference in control vs.
deprived groups was considered statistically significant if P ⬍ 0.05.
The limits of the confidence interval are defined as 2.5% and 97.5%
percentiles of the resampled quantities of interest computed from thegroup. We tested the difference in mean firing rates (shown in Fig. 2)
and the difference in Chernoff information computed on the basis of
population average of the PSTHs (shown in Fig. 3). Furthermore, we
tested the difference in median membrane potential (shown in Fig. 5)
and the difference in median conductance/evoked reversal potential(shown in Fig. 7) to avoid sensitivity of the results to a small numberof outliers.
A color bar at the top of each panel in Figs. 2–5 and 7 indicates thetime at which the population represented by that color is significantly
greater than the other population using the bootstrap test (P ⬍ 0.05).
Initial slope and latency distributions shown in Fig. 6 were comparedusing the Wilcoxon rank sum test or ANOVA.
Data representation. In this article, we characterize population
statistics using bootstrap resampling (unless we mention otherwise).
For the quantity of interest, we quote the bootstrap median (BM),upper confidence interval (UCI), and lower confidence interval (LCI),J Neurophysiol • doi:10.1152/jn.00289.2016 • www.jn.org

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when the size of the time bin, ⌬, is small enough so that each bin does
not contain more than one spike. The maximum of the integral withrespect to the parameter ␣ was computed by discretely sampling therange with step size 0.01. If the difference between firing rate traces
f(t) and g(t) is small, the Chernoff information becomes equivalent to
the Fisher information, a measure widely used in neuroscience toquantify detectability of a small parameter change (Seung and Sompolinsky 1993; Toyoizumi et al. 2006). The Chernoff information ismore general than the Fisher information because it can also characterize large “distance.” An in-depth explanation about Chernoff information in the neuroscience context is given elsewhere (e.g., Kang
et al. 2004).
Receiver operating characteristic. For each stimulus condition, theoverlap between the distributions of spike counts in trials withwhisker and without whisker stimulation was calculated using receiver operating characteristic (ROC) analysis. The ROC curve wascreated by plotting the proportion of stimulus trials whose spikecounts were above the threshold against the proportion of null trials
whose spike counts were above the same threshold. This was repeatedfor various thresholds. The area under ROC (AUROC) was calculated
by measuring the area under the ROC curve. When the area was below
0.5, the area above the curve was taken instead. A larger AUROC
indicates that the two distributions are more separated. This was
repeated for variable upper limits of the time window in the range of
6 to 60 ms after the stimulus in 1-ms steps. The lower limit of the time
window was 5 ms after the stimulus.
Initial slope analysis. The initial slope of the PSPs was defined as
the maximum PSP derivative. When the maximum did not correspondto the initial part of the response, the whiskers were excluded from theanalysis by visual inspection (29 cells).
Latency analysis. Latency was defined as the first time point
following stimulation when the time derivative of the evoked PSP
crossed a threshold fixed at mean ⫾ 3 SD beyond the time derivativeof the spontaneous activity. After visual inspection, latency wascorrected if an obvious false positive was detected (3.8% of the cases).
In rare cases, the response was small enough that the derivative of the
PSP did not cross the threshold but the response was unambiguously
visible. In these cases, the latency was taken as the time of the
maximum PSP derivative (1.4% of the cases).
Conductance estimation. Because voltage clamp cannot be achieved
with high-access resistance electrodes, we used current-clamp recording for conductance estimation. A range of current injections was used
to maintain the cell hyperpolarized or slightly depolarized. We
avoided depolarizations that would recruit the nonlinearities of thecurrent-voltage (I-V) curve, as recommended by Monier et al. (2008).
Receptive fields were mapped during random alternation between
three to five different levels of current injection (⫺40 to ⫹20 pA) thatalways included the zero-current level. Recorded membrane potentialtraces were median-filtered with a 10-ms window to eliminate residual
spikes. For each whisker, at each time point t, a linear regression
model [v(t) ⫽ v0(t) ⫹ a(t)I, where v0(t) and a(t) are regression
coefficients relating injection current I to membrane potential v(t)]was fit to minimize the sum of squared errors in all recordings of thecell with the whisker stimulus. The regression coefficient trace wassmoothed [ã(t) and ṽ(t)] and differentiated [ȧ(t) and v̇(t)] with respect
to time both using the Savitzky-Golay filter. A third-order polynomial
was used, and the window length was 5 ms (1 ms for 2 cells with sharp

response). The overall results did not change if a 5-ms window wasused in all the cells.
First, total conductance and reversal potential were estimated on
the basis of the following equations, where C is the measured
capacitance of the cell:

PLASTICITY OF CORTICAL INFORMATION FLOW

which are respectively 50%, 97.5%, and 2.5% percentiles of thebootstrap samples. Likewise, we plot these three percentiles in eachpanel of Figs. 2–5 and 7.
RESULTSA

B

C

the principal whisker was located at the center of the grid (Fig.
2A). We applied a pseudorandom sequence to stimulate thewhiskers, comprising 50 stimuli for each of the 9 whiskers plus
a null period of no stimulation, which we used to estimate
spontaneous activity (Jacob et al. 2008, 2012). Evoked activity
was evaluated by subtracting spontaneous activity and averaging the response over 50 stimuli. Overall, the absolute level of
spontaneous and evoked activity reported (Fig. 2) cannot bedirectly compared with that of other studies due to the use of
sharp microelectrodes. However, the relative incidence of eachcell type is in agreement with the literature (de Kock et al.
2007).
Effect of deprivation on spontaneous activity. Spontaneous
activity was unchanged by deprivation in all but the L5RS cells(Fig. 2B). After whisker deprivation, the mean spontaneous
firing rate of L5RS cells located in the deprived row decreased
approximately fourfold in row-deprived animals (control:BM ⫽ 7.9 Hz, deprived: BM ⫽ 2.1 Hz). This difference was
highly statistically significant (P ⬍ 0.001, bootstrap test) andcan be seen in the prestimulus period of the PSTHs (Fig. 2, C
and D, L5RS). Spontaneous activity was unchanged for any
other cell type studied, including L5IB cells and cells locatedin other layers (see Fig. 2 and Table 1).
Effect of deprivation on evoked activity. Evoked activity wasaffected by deprivation, and the amplitude and direction of theeffect depended on cell type, layer location, and the identity ofthe stimulated whisker (trimmed or spared, Fig. 2, C and D).
For trimmed whiskers, the mean firing rate decreased to 71%

DE

Fig. 1. Cortical cell types studied in vivo in the barrel cortex using intracellular recording. A: schematic representation of the recording setup. B: distribution of
the depth below the pia of recorded cells. C: dendritic reconstruction of 5 cells filled with biocytin. In L2/3, we only encountered cells with a pyramidal
morphology. In L4, we recorded from both spiny stellate (left) and pyramidal cells (right). Both cell types were present in the sample but not treated separately
in the analysis for L4. In L5, we distinguished between thick tufted (left) and thin slender (right) pyramidal cells. D: characteristic responses of cells to somaticcurrent injection: an example of L5RS cell spiking (top) and an example of L5IB cell spiking showing the characteristic burst of spikes of decreasing amplitude
riding on an envelope of depolarization (bottom). E: comparison of the morphology of L5 neurons categorized as IB or RS by their spiking characteristics. Note
that, on average, IB cells had larger somata and longer, wider dendrites, and their dendrites bifurcated at a greater depth than for RS cells. **P ⬍ 0.01; ***P ⬍10⫺4, Wilcoxon rank sum test.
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Intracellular recordings were performed in vivo in the D-row
columns of the barrel cortex of juvenile rats (⬃P30; Fig. 1A).
Cortical layers were assessed by the depth from pia (deeper
L2/3, mentioned as L3 for simplification, L4, and L5, Fig. 1B).
A subset of these cells was studied morphologically (Fig. 1C).
L4 cells (n ⫽ 5) were categorized into stellate-like or pyramidal-like morphology; L3 cells (n ⫽ 4) typically had dendritic
branching within L2/3; and L5 cells (n ⫽ 43) were either thicktufted or thin slender pyramidal neurons, as found in earlier
studies (Simons and Woolsey 1984; Zhu and Connors 1999).
L5 cells were further classified as intrinsically bursting (L5IB)
or regular spiking (L5RS) according to their firing pattern in
response to current injection, and the classes correlated with
their morphology (Fig. 1, D and E; Jacob et al. 2012).
Sensory deprivation was induced by trimming the D-row
whiskers (Fig. 2A). After 10 days of deprivation, trimmed
whiskers were re-glued on the whisker stump for testingcortical responsiveness. Responsiveness was compared withthat in control animals, whose whiskers were trimmed andre-glued on the day of recording. To assess changes in thereceptive fields of recorded cells rapidly and automatically, weused a whisker stimulator containing 9 piezoelectric bimorph
wafers attached to 9 whiskers in a 3 ⫻ 3 square grid such that

7

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PLASTICITY OF CORTICAL INFORMATION FLOW

A

B

C

of control levels in L3 (P ⫽ 0.008, ART-ANOVA). In L5, themean firing rate of RS cells decreased to 36% of control levels(P ⫽ 0.0002) The mean firing rate evoked by trimmed whiskers was unaffected by deprivation for cells located in L4 (P ⫽0.20) and for IB cells in L5 (P ⫽ 0.07). In summary, trimming
the whiskers led to lower trimmed whisker responses in L3 andL5RS cells but not in L4 and L5IB cells, and the magnitude ofthe decrease was largest for L5RS cells (Table 1).
For spared whisker responses, the mean firing rate of
L5IB cells increased to 139% of control values, which wasstatistically significant (P ⫽ 0.009). However, no other cell
types showed changes in spared whisker responses (L3, P ⫽0.48; L4, P ⫽ 0.11; L5RS, P ⫽ 0.21) as shown in Fig. 2 andTable 1.
Effect of deprivation on sensory information coding. The
information a neuron receives about a stimulus depends in parton differences between the evoked and spontaneous activity.
The spontaneous activity of L5RS cells was reduced after
deprivation, which suggested that information might changeeven if spared whisker responses remained constant. Therefore,
we investigated deprivation-induced changes in information
coding across cortical layers and cell types. We quantified theD

Chernoff information (Chernoff 1952; Cover and Thomas
1991; Kang et al. 2004), which summarizes detectability ofwhisker stimulation on the basis of population responses(shown in Fig. 3). For each cell type, the Chernoff information
measures a distance between the time-varying population firing
rate under evoked and spontaneous conditions, assuming inhomogeneous Poisson spiking of neurons (see METHODS). Although sensory information is generally coded by more thanjust firing rate (de Ruyter van Steveninck et al. 1997), including pattern of firing such as bursts, such extra features were notprominent in our data, possibly because of the relatively low
spiking activity and the sparse stimulation protocol applied inthis study. Chernoff information was calculated as accumulating with each 1-ms time bin from 1 to 60 ms poststimulus.
Aggregate Chernoff information about the stimulus was contained in the last time window (60 ms) and for each response
appeared to reach an asymptote by 60 ms (see Fig. 3). To
obtain the Chernoff information in an unbiased way based onrare spiking events, we calculated Chernoff information of the
population mean responses rather than the single-cell responses. However, the results were qualitatively similar
when the information was calculated for individual cells

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Fig. 2. Methodology for measuring the effect of whisker row deprivation on sensory responses in a deprived
barrel cortex column. A: deprivation protocol. Left, theD-row whiskers are trimmed for 10 days, leaving only
the whisker stump. The D-row whiskers are glued to thestump before mechanical stimulation; for the control
case, D-row whiskers are trimmed and then glued
immediately. Right, schematic representation of a stimulation sequence. Receptive fields are tested with a9-whisker stimulator arranged in a 3 ⫻ 3 grid with thedeprived D-row (red) at the center. Each line represents
the position of a whisker as a function of time. One
stimulation sequence comprises 1) a random permutation of stimulations of each of the 9 whiskers (colored
trapezoids) and a time event without stimulation (grayrectangle) and 2) an intracellular injection of current at
the end to test cell resistance (bottom line). Interwhisker intervals and an expanded trace to show thetime course of the stimulus (bottom inset) are indicated.
B: plasticity of baseline firing rate. Bars and error bars
show the median and 95% confidence interval (bootstrap). Note that only the L5RS cells change theirbaseline firing rate in response to deprivation. C: plasticity of response to trimmed whiskers. Drawings at top
are schema showing the positions of the whiskers included in the analysis (control, black; deprived, red).
Population PSTHs of the response to trimmed whisker
stimulation are plotted for each category of cell. Theline shows the average firing rate, and the shaded area
represents the 95% confidence interval (bootstrap). For
each time point, control and trimmed whisker responses
are compared using statistical test (bootstrap test). The
horizontal bars above the graphs indicate the time
points for which there is a significant difference (P ⬍0.05, bootstrap test) between the time plots (depression,
black; potentiation, red). At right, the bar charts show
the area (calculated after subtracting spontaneous activity; scale bar, 0.5 spike/stimulus) and peak (scale bar,
50 Hz) of the population PSTHs; error bars show 95%
confidence intervals (bootstrap). D: plasticity of response to the spared whiskers recorded in the deprived
barrel column. Conventions are the same as in C exceptthat potentiation and spared whiskers are coded blue.
*P ⬍ 0.05, bootstrap test.

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9

Table 1. Spiking properties
Control
Layer(Spared/Trimmed)Mean

L3 (T)
L3 (S)
L4 (T)
L4 (S)
L5IB (T)
L5IB (S)
L5RS (T)
L5RS (S)

10
10
14
14
27
27
23
23

0.677
0.495
1.24
0.71
0.864
0.692
0.685
0.529

L3
L4
L5IB
L5RS

10
14
27
23

2.35
2.69
12.9
7.93

Lower
95% CI

Upper
95% CINo. ofcells

Mean

Total evoked (3–103 ms), spikes/stimulus
0.439
0.896
13
0.482
0.302
0.746
13
0.417
0.968
1.55
12
0.932
0.541
0.889
12
0.866
0.62
1.13
22
0.684
0.538
0.848
22
0.959
0.485
0.887
21
0.25
0.389
0.658
21
0.654
Baseline (⫺40 to ⫺10 ms), Hz
1.54
4.37
13
2.09
1.98
3.74
12
2.47
10.8
15.4
22
13.5
6.25
9.8
21
2.14

Lower
95% CI

Upper
95% CIP Value

0.254
0.289
0.601
0.681
0.45
0.792
0.127
0.513

0.69
0.557
1.32
1.1
0.913
1.13
0.4
0.823

0.00760*
0.47950.19686
0.11240.06672
0.00946*0.00022*0.21064

1.26
1.67
11.6
1.6

3.24
3.45
15.6
3.8

0.65
0.701
0.683
0*

Suprathreshold responses of neurons in different layers of the cortex to stimulation of the whiskers are tabulated along with the spontaneous firing rates. The
mean firing rate for evoked responses are estimated over the period 3–103 ms poststimulus after subtracting spontaneous activity. The spontaneous firing rate
period is estimated over ⫺40 to ⫺10 ms before the stimulus (Hz). Upper and lower 95% confidence intervals are calculated using the bootstrap method. P values
compare control and deprived values using the aligned rank transform (ART) ANOVA test (evoked) or bootstrap test (baseline). *P ⬍ 0.05. T refers to trimmed
whisker and S to spared whisker stimulation.

(data not shown). This result suggests that the variability of
sensory response in the current experiment was relatively
small within each cell type and emphasizes the robust natureof the finding.
In control undeprived animals, Chernoff information was
maximal in L4 cells. Whiskers in the same row as the principal
whisker, corresponding to the trimmed row in deprived animals, had bootstrapped Chernoff information of BM ⫽ 0.36
[UCI ⫽ 0.47, LCI ⫽ 0.26, nWC ⫽ 40 (14 cells)]. In the flanking
rows, which are spared in the deprived animals, Chernoff
information reached median BM ⫽ 0.15 [UCI ⫽ 0.22, LCI ⫽0.11, nWC⫽ 77 (14 cells)]. In control animals, Chernoff information for both flanking and same-row whiskers decreased in
the order L4 ⬎ L3 ⬎ L5IB ⬎ L5RS.
For all cell types except L5RS cells, the effect of whisker
deprivation on Chernoff information matched the changes in
evoked firing rate. After deprivation, Chernoff information was
unchanged in L4, which retained the greatest information in
the column (as with undeprived control animals). For thedeprived-row whiskers, Chernoff information was significantly decreased in L3 and L5RS cells [L3: control BM ⫽0.21, nWC ⫽ 30 whisker cell pairs (10 cells), deprived
BM ⫽ 0.11, nWC ⫽ 36 (13 cells), P ⫽ 0.030, bootstrap test;
L5RS: control BM ⫽ 0.13, nWC ⫽ 60 (23 cells), deprived
BM ⫽ 0.058, nWC ⫽ 58 (21 cells), P ⫽ 0.018, bootstraptest] and delayed in L5IB cells, but the order by which
information decreased by layer remained unchanged.
The situation was different for the spared whisker responses.
In L4 cells, Chernoff information was not significantly increased, though it was advanced in time (Fig. 3). In L5 cells,
Chernoff information was significantly increased (L5IB
spared: P ⫽ 0.032, L5RS spared: P ⬍ 0.001, bootstrap test)
and in addition, the increase in information was substantiallyadvanced in time for the L5RS cells. Finally, there was no
significant change in spared whisker information in L3 (P ⫽0.27). As a consequence, the ordering of information for sparedwhisker stimulation was reorganized by sensory deprivationsuch that activity in L5RS cells contained almost as much

Chernoff information as in L4 cells (BM ⫽ 0.17 vs. 0.24,
respectively) and far more than in L3 and L5IB cells (BM ⫽0.070 and 0.133, respectively). Therefore, sensory deprivation
changed the order of information representation for sparedwhiskers within a deprived barrel column to L4 ⬎ L5RS ⬎L5IB ⬎ L3.
Although Chernoff information takes into account changes
in the time course of neural response, we also used a simpler
ROC analysis based on spike count to check the robustness ofthe finding (Fig. 4). The results of the ROC analysis and theChernoff information analysis were very similar in that theeffect of whisker trimming produced the same direction ofchange in each case. The only difference was that the sparedwhisker response of L5IB cells did not show a significant
difference under ROC analysis despite the increased spikecount. In contrast, L5RS cells, which were of particular interest, showed a robust increase in sensory detection performanceby either measure.
Plasticity of subthreshold responses. To explore neuronalmechanisms underlying the deprivation-induced changes insensory information representation, we analyzed membranepotential in each group of cells. First, we tested for differencesin “resting” membrane potential of cells in different layers(Table 2). We found that there was no difference in mean
resting membrane potential for cells in L3, L4, and L5IB but
that L5RS cells showed a significant hyperpolarization from⫺60.7 to ⫺65.6 mV in deprived animals (P ⬍ 0.006, bootstraptest). This is consistent with the significant decrease in spontaneous action potential firing rate for L5RS cells (Table 1).
Figure 5, A–C, shows example traces and distribution of
ongoing membrane potential activity for L5RS cells with andwithout whisker deprivation. Deprivation did not induce a
global shift of the membrane potential distribution toward
hyperpolarization, but rather induced greater losses for depolarized membrane potential values.
Next, we analyzed the trimmed whisker-evoked postsynaptic potentials (tPSPs) and the spared whisker-evoked postsynaptic potentials (sPSPs) in L3, L4, L5IB, and L5RS cells (Fig.

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No. ofcells

Deprived

10

PLASTICITY OF CORTICAL INFORMATION FLOW

A

0.4

0.4

0.2

0.2

0

0

0.4

0.4

0.2

0.2

0

0

D

A

B

Fig. 3. Chernoff information contained in spike trains as a measure of plasticity
of sensory responses. A: trimmed whiskers. For the different layers and cell
types, Chernoff information between spontaneous activity and population
PSTH is plotted as a function of increasing time window sizes starting attime 0 after stimulation. The horizontal bar above each plot indicates thetime at which a significant increase (blue) or decrease (black) in Chernoff
information occurs due to sensory deprivation (bootstrap test). B: sparewhiskers. Chernoff information is plotted for cells in each layer using thesame conventions as in A. Note that potentiation occurs in all layers except
L2/3. C: summary of median Chernoff information for the largest window(0 – 60 ms) as a function of cell types for trimmed whiskers. Error bars
represent 95% confidence interval. D: same conventions as in C but forspared whiskers. *P ⬍ 0.05, ***P ⬍ 0.001, bootstrap test.

5, D and E, Table 2). For L3 cells, whisker deprivation
produced depression of trimmed whisker responses measured
by peak of median tPSP, which decreased to 65% of control
values (P ⫽ 0.04, ART-ANOVA), and initial slope of tPSPs,
which decreased to 54% of control values [control: median ⫽0.84 V/s, nWC ⫽ 35 (12 cells); deprived: median ⫽ 0.46 V/s,nWC ⫽ 36 (13 cells); P ⫽ 0.015, Wilcoxon’s rank sum test].
For L4 cells, we observed no changes in the peak tPSP (P ⫽0.25, ART-ANOVA) or tPSP slope (P ⫽ 0.63, Wilcoxon’s
rank sum test).
For L5 cells, tPSP responses were not significantly affected
in general, except for a significant slope reduction for L5RS
cells (P ⫽ 0.02, Wilcoxon’s rank sum test). Together withthe hyperpolarization of resting membrane potential in thispopulation following the deprivation, this naturally accounts
for the deprivation-induced decrease in the firing rate response to trimmed whiskers in L5RS cells. Conversely, forL3 cells, the decrease in firing rate caused by deprivation isFig. 4. Area under receiver operating characteristic curve (AUROC) calculated
independently for each cell and whisker. A: trimmed whiskers. For thedifferent layers and cell types, AUROC between distributions of spike counts
in trials with whisker stimulation and in null trials without stimulation isplotted as a function of increasing time window upper limit starting at time 6
ms after stimulation. Time window lower limit is 5 ms after stimulation. The
horizontal bar above each plot indicates the time at which a significant increase(blue) or decrease (black) in mean AUROC occurs due to sensory deprivation(bootstrap test). B: spare whiskers. AUROC is plotted for cells in each layerusing the same conventions as in A. Shaded areas represent the 95% confidence
interval.

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C

directly correlated with a decrease in membrane potential
depolarization.
For spared whiskers responses, L3 and L4 sPSPs were
unchanged overall after deprivation. However, sPSPs wereincreased in L5IB cells as judged by the peak of the mediansPSP, which increased to 144% of control values (P ⫽ 0.0005,
ART-ANOVA), and the sPSP initial slope, which increased to132% of control [control: median ⫽ 0.44 V/s, nWC⫽111 (19cells); deprived: median ⫽ 0.58 V/s, nWC ⫽ 98 (16 cells), P ⬍0.001, Wilcoxon’s rank sum test]. Finally, for L5 RS cells,
only the slope of the sPSPs was increased to 139% [control:
median ⫽ 0.32 V/s, nWC ⫽ 80 (17 cells); deprived: median ⫽0.44 V/s, nWC ⫽ 106 (17 cells), P ⫽ 0.014, Wilcoxon’s rank
sum test], but not the peak of the sPSP (Table 2). This sharper
rise of sPSPs after whisker deprivation is consistent with theshorter latency spiking response to spared whiskers in thispopulation. We explore later whether this change involveschanges in excitatory and inhibitory synaptic conductances.
Plasticity of response latency. The relative latencies recorded in the different groups of neurons provide additional
information on how sensory signals are sent to the cortex andhow they travel through layers. The latency of response to
remote surround whisker stimulation is much greater than thelatency of response to whiskers positioned closer to the center

BPLASTICITY OF CORTICAL INFORMATION FLOW

11

Table 2. Membrane potential
Control
Layer(Spared/Trimmed)

Deprived

MedianLower
95% CI

14
14
15
15
27
27
23
23

4.94
3.11
6.81
3.68
4.04
3.39
2.83
2.08

4.16
2.71
5.43
3.11
3.09
2.71
2.03
1.63

Layer

No. of
cells

Mean

Lower
95% CI

L3
L4
L5IB
L5RS

14
15
27
23

⫺61.35⫺66.30⫺63.69⫺60.74

L3 (T)
L3 (S)
L4 (T)
L4 (S)
L5IB (T)
L5IB (S)
L5RS (T)
L5RS (S)Lower
95% CINo. ofcells

MedianLower
95% CI

Upper
95% CIP ValuePeak membrane potential, mV
6.87
13
3.84
13
7.63
12
4.59
12
4.99
22
3.99
22
3.91
21
2.68
21

3.23
2.81
5.44
3.9
4.57
4.89
2.3
2.43

2.33
2.47
2.92
2.67
3.38
3.48
1.69
1.85

4.8
3.82
7.35
5.27
5.8
5.75
2.99
3.08

0.03578*
0.872480.248450.86453
0.719070.00048*0.26878
0.41965

No. of
cells

Mean

Lower
95% CI

Upper
95% CIP Value

Resting membrane potential, mV⫺58.35⫺64.5713⫺62.03⫺71.7412⫺60.98⫺66.3022⫺58.45⫺63.2021⫺64.90⫺63.02⫺65.39⫺65.55⫺61.33⫺59.33⫺62.63⫺62.57⫺68.99⫺66.56⫺68.52⫺68.54

0.162
0.122
0.052
0.006*Upper
95% CI

Membrane potential responses to stimulation of the whiskers (with spikes removed) are tabulated along with the resting membrane potential for neurons indifferent layers of the cortex. Median membrane potentials for evoked responses and means for resting potential are shown together with the upper and lower
95% confidence intervals, which are calculated using the bootstrap method. P values compare control and deprived values using the ART-ANOVA test (peak)or bootstrap test (resting). *P ⬍ 0.05. T refers to trimmed whisker and S to spared whisker stimulation.

of the receptive field (Armstrong James and Fox 1987), and its
estimation is more sensitive to noise. Therefore, we consideredlatency independently for each whisker rather than averaging
all trimmed and all spared whiskers as described above. To
study the plasticity of PSP latencies, we plotted latencies
against the Euclidian distances between the corresponding
whisker positions and a center of mass (CM) of the multiwhisker receptive field, which is evaluated using the coordinates of
the whisker positions on the face. To estimate the CM independently from sensory deprivation, we used the CM of
evoked local field potentials recorded in L4 during the same
electrode penetration (Fig. 6A). The selected recording sites
had one dominant principal whisker in the D-row that largely
defined the center of the receptive field, but it could be offset
by secondary inputs from surrounding whiskers. As expected,
both latency and variability of latency distribution increased
with the distance of the whisker from the receptive field center(Fig. 6B, for all cell types, P ⬍ 0.01, ANOVA).
In the control condition, latency also increased from L4 andL3 to L5 (respectively for L3, L4, L5IB, and L5RS cells:
median latency ⫽ 9.6, 10.3, 11.4, and 13.5 ms; UCI ⫽ 10.3,
11, 12.1, and 14.6 ms; LCI ⫽ 9, 9.9, 11.1, and 12.4 ms). In the
deprived condition (Fig. 6C), the latency of trimmed whisker
tPSPs was unchanged for all layers. For spared whiskers, thelatency of sPSPs decreased significantly in the entire L5RS
cell’s receptive field (P ⬍ 0.001, ANOVA) and in L4 mostly
away from the receptive field center (P ⬍ 0.01, ANOVA).
Latencies did not change in L3 and L5IB cells. Interestingly,
the latency of sPSPs in L5RS cells (median ⫽ 10.5 ms, UCI ⫽12.4 ms, LCI ⫽ 9.2 ms, nWC ⫽ 83) was shorter than that in L3
neurons (median ⫽ 12.3 ms, UCI ⫽ 13.4 ms, LCI ⫽ 10.6 ms,
nWC ⫽ 80, P ⫽ 0.05, ANOVA) and L5IB cells (median ⫽ 13.2
ms, UCI ⫽ 14.4 ms, LCI ⫽ 12.1 ms, nWC ⫽ 88, P ⬍ 0.01,
ANOVA) but was not different from that in L4 neurons(median ⫽ 9.3 ms, UCI ⫽ 10.7 ms, LCI ⫽ 8.7 ms, nWC ⫽ 65,
P ⫽ 0.13, ANOVA). Moreover, latency of the 10% most rapidsPSPs was significantly shorter in L5 RS cells (median ⫽ 5.2ms) than in L3 cells (median ⫽ 7 ms, P ⬍ 0.001, ANOVA) andin L5IB cells (median ⫽ 8.4 ms, P ⬍ 0.001, ANOVA). This
result suggests that short-latency potentiation in L5RS cells is
unlikely to be derived either from L3 or L5IB cells.
Conductance analysis for L5 cells. To gain some insight into
the excitatory and inhibitory components of whisker responses and their plasticity, we repeated sets of stimuli
under various levels of injected current to calculate synaptic
conductance and reversal potential (Fig. 7A). We recorded
conductance for L5 receptive field responses in control anddeprived animals. We found that the decrease of latency
observed in L5RS cells was associated with both excitatory(P ⬍ 10⫺4 for trimmed whiskers and P ⬍ 10⫺6 for sparedwhiskers, Wilcoxon’s rank sum test) and inhibitory components (P ⬍ 10⫺6 for trimmed whiskers and P ⬍ 10⫺5 forspared whiskers; Fig. 7B).
For trimmed whisker responses, even though the medianexcitatory and inhibitory conductance peaks were both decreased (Fig. 7C; P ⫽ 0.018 for excitatory conductance andP ⫽ 0.018 for inhibitory conductance, nC ⫽ 6 cells, ARTANOVA), the effects largely canceled one another out toproduce no net change in the reversal potential over the sametime interval.
For spared whisker responses, both excitatory (gE) andinhibitory (gI) conductance peaks increased significantly (P ⫽0.003 and P ⫽ 0.03, respectively, ART-ANOVA). The earlypart of the median excitatory conductance waveform from 10
to 17 ms was the main source of the effect (P ⬍ 0.05, bootstrap
test; Fig. 7C). In addition, the median reversal potential was
significantly increased during a similar period from 9 to
26 ms (P ⬍ 0.05, bootstrap test), and the peak reversal
potential was 209% greater in deprived compared with control
animals (Table 3: P ⫽ 0.026, bootstrap test; P ⫽ 0.007, ARTANOVA). Both observations confirmed a stronger increase of
excitatory conductance than of inhibitory conductance. Because

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No. ofcells

12PLASTICITY OF CORTICAL INFORMATION FLOW

A

B

D

C

E

the earliest part of the subthreshold waveform is related to theperiod when spikes are produced in response to whisker stimulation, the increase in reversal potential during the first 30 ms of the
response most likely explains the increase in spike firing to thespared whiskers during this period (see above on RS cell suprathreshold responses).
For L5 IB cells, we found no significant difference in thelevel or latency of total conductance with deprivation. Although all whisker responses showed a trend toward morepositive reversal potentials favoring excitatory conductance(data not shown), none were significant (Table 3).
DISCUSSION

We found that plasticity induced by row deprivation alters
the distribution of sensory information within and between

the different layers of the cortical columns. To summarize,
no major changes were observed in L4 cells except for adecrease in latency to the spared whiskers; the only change
we observed in L3 cells was a decrease in response totrimmed whiskers; L5IB cells underwent a small depression
to trimmed whisker inputs and a global potentiation tospared whiskers; and finally, L5RS cells exhibited a remarkable form of plasticity resulting in the largest change in
information that we observed. L5 cells showed a decrease inspontaneous activity, the potentiation of a short latency
excitatory input from the spared whiskers and a decreased
response to the trimmed whiskers. We discuss below someof the substrates and pathways for L5 plasticity that was
clearly distinct from the more conventional effects observedin L4 and L3.

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Fig. 5. Plasticity of membrane potentials (Vm) and postsynaptic potentials (PSPs) along the barrel cortex column. A: 10 s of ongoing activity for a L5RS cellin a control rat. B: 10 s of ongoing activity for a L5RS cell in a deprived rat. C: for each L5RS cell, cumulative density of Vm during the blank stimuli wascalculated. For statistical robustness, outlier cells were removed (2 cells with the lowest median Vm value and 2 cells with the highest median Vm value for bothdeprived and control). Thick line shows the mean Vm cumulative distribution for control (black) and deprived (red) cells. Shaded areas delineate the bootstrap
confidence interval (95%). D: trimmed whiskers. For the different layers and cell types, median tPSPs are plotted. The horizontal lines above the graphs indicate
the time points for which there is a significant difference (P ⬍ 0.05, bootstrap test) between control and trimmed whiskers (depression, black; potentiation, red).
At right, distribution of tPSP initial slope is plotted as a histogram (scale bar, 5 units). The bar charts represent area and peak of median tPSPs and 95% confidence
interval (scale bars, 0.2 s·mV for area and 5 mV for peak). E: spared whiskers. Averaged sPSPs are plotted for the different layers and cell types. Conventions are thesame as in D except that potentiation is coded blue and the scale bar for initial slope distribution is 20 units. *P ⬍ 0.05, **P ⬍ 0.001, bootstrap test.

PLASTICITY OF CORTICAL INFORMATION FLOW

A

13

B

C

Pathways underlying short-latency responses in L5. There isa long history documenting the short-latency thalamic ventral
posteromedial nucleus (VPm) input to L5 of the somatosensory
cortex. Electron microscopy studies have shown that VPm
projections make contact with cells in all layers of the barrel
cortex except L2, and in particular on L5 (White 1978; Whiteand Hersch 1982). Short-latency whisker responses, concurrent
with those in L4, were observed in L5b almost a quartercentury ago (Armstrong-James et al. 1992), and in vitro studies
pioneering the thalamocortical slice preparation concurrently
demonstrated VPm input to L5 cells (Agmon and Connors
1992). More recent studies have further documented the presence of thalamic input to L5 in both the mouse and rat(Constantinople and Bruno 2013; Petreanu et al. 2009; Rah et
al. 2013; Wright and Fox 2010). In the present study we foundthat an early component of the RS cells response to whisker
stimulation was potentiated by row deprivation and that potentiation was related in time to an increase in an excitatory
conductance. Given the latency of the response comes before
any other cortical cell responds except those in L4 of theprincipal barrel, the most likely source of the excitation is adirect input from VPm. At present, it is not clear why short-latency input should potentiate in RS cells and not in IB cells.
The original report of Agmon and Connors (1992) suggested
that IB cells do not receive thalamic input whereas RS cells do.
However, there is evidence of the opposite in the auditory
cortex (Sun et al. 2013) and in the barrel cortex (Bureau et al.
2006).
For the thalamic input to account for the increased shortlatency component generated by spared whisker stimulation,
the VPm input would need to convey excitation to a nonprincipal whisker barrel. There are two possibilities: first, branchesof thalamic afferents innervating their principal barrels mightgrow into the neighboring deprived barrel (Oberlaender et al.
2012) during the 10-day deprivation period; second, the nonprincipal whisker inputs that potentiate might already exist,
and there is evidence for this view. Blocking intracorticalactivity with muscimol and locally disinhibiting the recorded
cell reveals double-whisker responses or multiwhisker responses in some L5 cells (Wright and Fox 2010).
Potentially, the short-latency input to L5 RS cells mightarise from L4 in the neighboring barrel. There is functional
evidence from paired recordings, glutamate uncaging, andoptogenetic stimulation studies that L4 projects to L5 (Feld-

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Fig. 6. Plasticity of PSP latencies along the barrel cortex column. A: methods for calculating the spatial distance between each whisker and center of mass (Wminus CM) and PSP latencies. Local field potentials (LFPs) were recorded in L4 with the same electrode and at the same penetration used for intracellular
recordings. Left, example of LFP responses to 8 different whiskers. The initial slope of the negative potential is used to calculate the CM of the receptive field.
Right, schematic representing the position of the whiskers (gray circles) and the CM (red cross) and the distance between whisker C2 and the CM (dashed line)
in a Cartesian whisker space. In the whisker space, distance between rows and between arcs is arbitrarily set to 1. The straddler’s positions (delta and gamma)
are set at halfway between the two rows. B: distribution of PSP latencies for L4 recordings. The distance between whisker and the L4 LFP CM is plotted against
PSP latencies (gray diamonds). Distances are grouped in 0.5 intervals of whisker space to calculate the median (black lines). Error bars show the 95% confidence
interval (bootstrap). C: plasticity of latencies. For each 0.5 distance interval, medians of PSP latencies are plotted for control responses (black), trimmed whisker
responses (red), and spared whisker responses (blue). Error bars show the 95% confidence interval (bootstrap). Because recordings were always in the deprived
column, the distance W minus CM was never larger than 1.5 for trimmed whiskers and never smaller than 0.5 for spared whiskers. Significant differences
between control and deprived cases are tested with Wilcoxon’s rank sum test. Note the highly significant latency shifts for L4 and L5RS spared whisker
responses (**P ⬍ 0.01; ***P ⬍ 0.001).

14

A1

PLASTICITY OF CORTICAL INFORMATION FLOW

B

A2

Fig. 7. Plasticity of excitatory and inhibitory conductances in L5RS cells. A1:
evoked conductances and reversal potential calculated on a control L5RS cell.
Left, PSPs were calculated for different levels of injected currents. Middle,
reversal potential (Erev). Right, total (Grest subtracted) excitatory (Gex) andinhibitory (Gin) conductances. A2: evoked conductances and resting potential
calculated on a control L5IB cell. Same conventions as in A1. B: plasticity oflatency of inhibitory (top) and excitatory (bottom) conductances to control(black), trimmed (red), and spared whiskers (blue). Same conventions as Fig.
6C. **P ⬍ 0.01, Wilcoxon rank sum test. C: plasticity of reversal potential(top), inhibitory (middle), and excitatory (bottom) conductances. Same conventions as Fig. 5, D and E. The bar charts represent areas (scale bars: Erev, 0.1
s·mV; Gin, 0.1 s·nS; Gex, 0.04 s·nS) and peaks (scale bars: Erev, 5 mV; Gin, 4
pS; Gex, 1 nS). Error bars indicate 95% confidence interval. *P ⬍ 0.05,
bootstrap test.

meyer et al. 2005; Petreanu et al. 2009; Schubert et al. 2001).
Furthermore, anatomical studies show axons projecting ventrally from L4 spiny stellate cells, mainly in the column, butwith some overlap into neighboring columns, including subgranular layers (Lubke et al. 2000; Narayanan et al. 2015).
Basal dendritic branches of L5 pyramidal cells spanning into
the neighboring barrel could be engaged by axons confined tothe home column. Glutamate uncaging studies in row-deprived
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Cneighboring spared columns to L5IB in the deprived column
can potentiate in response to deprivation (Jacob et al. 2012),
but this has not been demonstrated for L5RS cells. Finally, L6
cells, known to display short-latency responses to whisker
stimulation (Constantinople and Bruno 2013; de Kock et al.
2007) and to project axons to L5 (Narayanan et al. 2015), arealternative candidates for inducing the short-latency responses
in L5RS cells. However, neither L4 nor L6 inputs to L5RS
cells were found to potentiate (Jacob et al. 2012).
Pathways underlying spontaneous activity in L5. Information about the principal whisker decreases significantly within
the deprived column for all layers except L4, whereas information about the spared whiskers increases for all layers except
L3. In addition, spared whisker information builds up in the
L5RS cells after stimulation more rapidly than in control cases,
partly due to potentiation of a short-latency excitatory input(vide supra) but also due to a decrease in spontaneous activity.
Spontaneous activity varies according to the anesthetic level,
the sleep states, or, in the awake animal, the conscious state,
and it might alter the Chernoff information for the RS cells andother cell types. Urethane anesthesia creates a state of deltawave activity where the EEG fluctuates at 0.5– 4 Hz due to theburst-pause activity of L5 neurons, similar to the condition
present in natural slow-wave sleep (Armstrong-James et al.
1985; Armstrong-James and Fox 1988). The burst activity is
generated partly by intracortical circuits, particularly via horizontal connections in L5 (Beltramo et al. 2013; Chauvette etal. 2010; Le Bon-Jego and Yuste 2007), and partly by thalamic
input originating in principal and intralaminar thalamic nuclei(David et al. 2013; Doi et al. 2007; Fox and Armstrong-James1986). The decrease in spontaneous activity in the L5RS cells
was accompanied by a hyperpolarization in membrane potential, suggesting a decrease in excitatory drive. The decrease inspontaneous activity would not appear to arise from a change
in principal thalamic input, because this appears to potentiate
in RS cells; it also would not appear to derive from a decrease
activity in the L3-to-L5 pathway, because L5 bursts of action
potentials persist when activity is abolished in supragranularlayers (Beltramo et al. 2013), and some degree of independence was observed between subgranular and supragranular
spontaneous activity (Reyes-Puerta et al. 2015). This suggeststhat a decrease in horizontal connections between L5 cells,
which are known to be important for spontaneous bursts ofaction potentials (Beltramo et al. 2013; Chauvette et al. 2010),
are more influential for the decrease in spontaneous activity. In
this respect, it is of interest that bursts of action potentials in IB
cells tend to precede those in RS cells (Chauvette et al. 2010),
which suggests that IB-to-RS cell connections may be depressed by whisker deprivation. Conversely, the IB cells stillshow normal levels of spontaneous activity, which is consistent
with the lack of depression of columnar pathways and potentiation of intracolumnar pathways onto L5IB cells (Jacob et al.
2012).
Compound sources of principal whisker depression. L2/3
provides a major input to L5 across various cortical areas(Hooks et al. 2011). In the barrel cortex, input from L2/3 cells
to L5b is important for principal whisker responses in L5b(Wright and Fox 2010). In the current row-deprivation experiments, the input from L2/3 to L5 is depressed within the
deprived column, and this is due to two main effects; first, theL4 input to L2/3 is depressed in the deprived column (Glaze-PLASTICITY OF CORTICAL INFORMATION FLOW

15

Table 3. Membrane conductanceControl
Layer(Spared/Trimmed)

Deprived

MedianLower
95% CI

L5IB (T)
L5IB (S)
L5RS (T)
L5RS (S)

6
6
6
6

0.823
0.701
1.38
0.55

0.696
0.465
0.78
0.268

L5IB (T)
L5IB (S)
L5RS (T)
L5RS (S)

6
6
6
6

2.62
0.94
2.49
0.933

1.72
0.602
1.39
0.314

L5IB (T)
L5IB (S)
L5RS (T)
L5RS (S)

6
6
6
6

3.88
4.66
3.49
2.66

2.9
3.11
2.41
1.85

L5IB
L5RS

6
6

283
188

126
113

Upper
95% CINo. ofcells

Excitatory conductance, nS
3.44
3
0.958
3
2.96
6
1.15
6
Inhibitory conductance, nS
9.1
3
1.37
3
5.36
6
1.5
6
Reversal potential, mV
5.45
3
5.74
3
6.66
6
4.14
6
Input resistance, M⍀
354
3
324
6

MedianLower
95% CI

Upper
95% CIP Value

0.98
1.23
0.771
0.842

0.37
0.487
0.342
0.557

1.94
2.18
1.31
1.55

0.26140.081611
0.018267*
0.0033439*

0.859
1.65
2.67
2.31

0.441
0.911
1.11
0.866

5.62
4.08
4.97
4.55

0.59498
0.092052
0.018054*
0.028516*

4.99
5.83
4.19
5.57

3.28
4.1
2.67
3.6

12.4
7.86
6.3
7.4

0.62465
0.19963
0.76240.0071428*

150
175

114
98

549
258

0.587
0.730

Excitatory and inhibitory membrane conductances during responses to stimulation of the whiskers are tabulated along with the reversal membrane potential
for neurons in L5 of the cortex. Input resistances are also indicated. The median peak of conductances and reversal potentials is shown together with the upperand lower 95% confidence intervals, which are calculated using the bootstrap method. P values compare control and deprived values using the ART-ANOVA
test. *P ⬍ 0.05. T refers to trimmed whisker and S to spared whisker stimulation.

wski and Fox 1996; Glazewski et al. 1998), and second, theL2/3 inputs to L5 are depressed for RS but not IB cells (Jacobet al. 2012). This set of circumstances would be expected tocreate a depression in L5IB cells and a greater depression in
L5RS cells; thus our observations support this model (Fig. 8).
A recent deprivation study in mice showed a loss of dendritic
spines in L4 pyramidal cells following whisker trimming(Miquelajauregui et al. 2015). L4 pyramidal and spiny stellate
cells could not always be distinguished in the present study, so
we did not analyze them separately. We did not find any

A

BFig. 8. Schematic depiction of the proposed model of circuit plasticity for L5
neurons. A: control case. Sensory information from the whiskers (bottom)
reaches L5 via two pathways, a direct thalamic input or through a cortical relay
L4 ¡ L2/3 ¡ L5. Two adjacent cortical columns are represented, but for
simplification a single L2/3 spot is drawn due to L2/3 relative homogeneity.
The model can easily be implemented to distinguish the columns in L2/3. We
do not distinguish L5 IB and RS cells for the control case. B: proposed circuit
plasticity for L5RS cells (left) and L5IB cells (right). Depression of pathway
strength is indicated with dashed red arrows, and potentiation with thick blue
arrows. For RS cells, a potentiation upstream of L2/3 should be considered.
The potentiation could be from direct thalamocortical synapses, but we cannot
exclude a L4 ¡ L5 potentiation, which is why the connection is included witha dashed blue arrow. For IB cells, potentiation arises at L2/3 ¡ L5 synapses.

significant changes in the L4 cells independent of subtype. A
more specific depression of L4 inputs might impact L5 plasticity. One other factor that might contribute to the lower
depression of L5IB cells is that the hyperpolarization activatedcurrent (Ih) is downregulated in the apical dendrites by whisker
deprivation, and this effect appears restricted to IB cells(Breton and Stuart 2009). Lower levels of Ih would be expected
to increase excitability of the IB cells to their diminished L2/3
input and to some extent counter the circuit effects.
Excitatory vs. inhibitory influences in expression ofplasticity. Inhibition is important for induction of plasticity;disinhibition occurs phasically and chronically during the earlystages of whisker deprivation in superficial layers (House et al.
2011; Katzel and Miesenbock 2014; Kelly et al. 1999; Li et al.
2014), but its role in expression of barrel cortex plasticity isless well established. For the spared whiskers, both excitatory
and inhibitory conductances were found to increase in L5RS
cells, although at different latencies, which rules out the idea of
disinhibition and supports the idea that potentiation is due toexcitatory inputs likely through excitatory synapse potentiation. For the spared whiskers, the increase in gE preceded thatin gI and therefore allowed excitation to escape the influence of
the inhibitory effect and depolarize the cell. For the deprived
whiskers, the concomitant increase of gE and gI canceled one
another out and led to no change. This finding is consistent
with previous studies showing that the phase relationshipbetween excitation and inhibition is crucial in creating the
response selectivity of neurons in the barrel cortex (Wilent andContreras 2005). Our results should be interpreted with caution, since all studies estimating conductance from somaticrecordings are biased toward perisomatic synapses (Williams
and Mitchell 2008). For L5 pyramidal cells, all excitatory input
pathways target the perisomatic dendrites in L5, even if VPmneurons also contact oblique dendrites in L4 and L2/3 inputs
also target the apical tuft (Petreanu and Svoboda 2009). For

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No. ofcells

16

PLASTICITY OF CORTICAL INFORMATION FLOWGRANTS
We acknowledge funding from RIKEN Brain Science Institute (to A.
Mitani and T. Toyoizumi), from the Brain/MINDS (Brain Mapping by Innovative Neurotechnologies for Disease Studies) supported by the Ministry of
Education, Science, and Technology (MEXT) of Japan (to T. Toyoizumi), andfrom the Medical Research Council (to K. Fox) for this work.

DISCLOSURES
No conflicts of interest, financial or otherwise, are declared by the authors.

AUTHOR CONTRIBUTIONS
V.J. and K.F. conception and design of research; V.J. performed experiments; V.J., A.M., T.T., and K.F. analyzed data; V.J., A.M., T.T., and K.F.
interpreted results of experiments; V.J., A.M., and T.T. prepared figures; V.J.,
T.T., and K.F. drafted manuscript; V.J., A.M., T.T., and K.F. edited andrevised manuscript; V.J., A.M., T.T., and K.F. approved final version ofmanuscript.

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