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Science. 2010 January 29; 327(5965): 587590. doi:10.1126/science.1179850.

The Asynchronous State in Cortical Circuits

Alfonso Renart1,*,, Jaime de la Rocha1,2,*, Peter Bartho1,3, Liad Hollender1, Nstor
Parga4, Alex Reyes2, and Kenneth D. Harris1,5,6
1Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, NJ 07102, USA
2Center

for Neural Science, New York University, New York, NY 10003, USA

3Institute

of Experimental Medicine, Hungarian Academy of Sciences, Budapest 1083, Hungary

4Departamento
5Smilow

de Fsica Terica. Universidad Autnoma de Madrid, Madrid 28049, Spain

Research Center. New York University Medical School, New York 10016, USA

Abstract
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Correlated spiking is often observed in cortical circuits, but its functional role is controversial. It is
believed that correlations are a consequence of shared inputs between nearby neurons and could
severely constrain information decoding. Here we show theoretically that recurrent neural networks
can generate an asynchronous state characterized by arbitrarily low mean spiking correlations despite
substantial amounts of shared input. In this state, spontaneous fluctuations in the activity of excitatory
and inhibitory populations accurately track each other, generating negative correlations in synaptic
currents which cancel the effect of shared input. Near-zero mean correlations were seen
experimentally in recordings from rodent neocortex in vivo. Our results suggest a re-examination of
the sources underlying observed correlations and their functional consequences for information
processing.

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The spiking activity of neurons is often correlated within local cortical populations (1-4). While
correlations could be a signature of active information processing (5,6), they can also impair
the estimation of information conveyed by the firing rates of neural populations (2,7,8) and
might limit the efficiency of an organism for performing sensory discriminations (2,7). Under
certain conditions correlated spiking is an inevitable consequence of shared pre-synaptic input
(9,10). In general, however, the overall contribution of shared input to correlation magnitudes
measured in vivo is unclear, as measured correlations could reflect mostly covariations in
activity due to cognitive or external variables outside the control of the experimenter (11-13).
To investigate the relationship between correlations and shared input, we studied theoretically
the correlation structures characteristic of densely connected recurrent networks.
We start by considering how the correlation between a single neuronal pair depends on the
fraction p of shared inputs and the degree rin to which the inputs are themselves correlated.
The effect of shared input can be isolated by considering presynaptic neurons that fire
independently (rin = 0). Both excitatory (E) and inhibitory (I) shared inputs cause positive
correlations of a moderate magnitude in the synaptic input and spiking activity of the
postsynaptic pair (Fig. 1A-B) (9, 14). Spiking correlations rin between inputs, on the other
hand, have a major impact on the output correlation rout of the post-synaptic pair. When all
inputs are E, very weak input correlations give rise to strongly correlated synaptic currents and

To whom correspondence should be addressed; [email protected]..

6New address: Departments of Bioengineering, Electrical and Electronic Engineering, Imperial College, London SW7 2AZ, UK
*These authors contributed equally to this work.

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output spikes (Fig. 1C). This occurs because, when p and rin are small, the correlation c of the
two input currents is approximately equal to

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(1)

(15), where N is the number of synaptic inputs, resulting in a very large gain in the relationship
between rin and rout (Fig. 1E, upper solid curve). The situation changes when both neurons
receive I as well as E inputs. Correlations between E or between I neurons lead to strongly
correlated excitatory and inhibitory synaptic currents (Fig. 1F, red and green traces). However,
when E and I inputs are themselves correlated, large fluctuations in the excitatory and inhibitory
currents occur simultaneously (Fig. 1F, asterisks) and cancel, leading to a significant reduction
in the correlation of the total synaptic currents c and output spikes (Fig. 1F, black and gray
traces). Correlations between E and I inputs thus decorrelate the synaptic currents to
postsynaptic neurons (16).

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To investigate whether such decorrelation can arise spontaneously from the dynamics of a
recurrent network, we analytically characterized the behavior of correlations in a simple
recurrent circuit of binary neurons (17-19). The network consists of two populations (of size
N) of E and I neurons connected randomly, both receiving excitatory projections from an
external (X) population of N cells (Fig. 2A). The network has two key properties: first, the
connectivity is dense so that the connection probability p (and thus the mean fraction of shared
input) is fixed independently of the network size (e.g. p = 0.2 (20) as in Fig. 2). Second, the
synaptic couplings are strong such that only a small fraction of a cells excitatory inputs is
enough to evoke firing (Fig. 2B); in the model, although the average number of inputs is
proportional to N, the number of excitatory inputs needed to induce firing is only proportional
(19). Our analysis showed that, even in the presence of shared input, the network settles
to
into a stationary state in which the population-averaged firing correlation r is very weak, if
inhibition is sufficiently strong and fast. In fact, in networks of different sizes, r decreases
inversely proportional to N (Fig. 2C, open squares and (17)-section 1.3), a signature of
asynchronous networks (18). In an asynchronous state, the variance of the population-averaged
instantaneous activity scales in the same way as if the neurons were completely independent
as 1/N. Thus, correlations in the asynchronous state do not qualitatively constrain averaging
of activity across neural populations (Fig. S2) (18).

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Asynchronous activity persists in the presence of shared input due to a spontaneously generated
tracking of fluctuations in the population-averaged instantaneous activities mE(t) and mI(t) of
the E and I neurons (Fig. 2D and (17)-section 1.4). Specifically, mI(t) tracks mE(t) with a small
lag (EI-Lag), and they both closely follow the external instantaneous activity mX(t). In larger
networks, tracking becomes more accurate, and becomes perfect in the large N limit,
(2)

where AE and AI are constants which depend on the network architecture. Tracking occurs
because, when the connectivity is strong and dense, even small random fluctuations in
, are large enough to recruit inhibitory
instantaneous excitatory activity, of order
feedback.
Tracking of the instantaneous population activities is equivalent to a precise cancellation of
the different components of the (zero-lag) population-averaged current correlation c (Fig. 2E
and (17)-section 1.5). Because the synaptic current to each cell consists of an excitatory and
an inhibitory component, the average current correlation across cell pairs, c, can be decomposed

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into cEE, cII and cEI (the term cIE = cEI). Both cEE and cII are positive and large, i.e., independent
of N, for large networks (Fig. 2C, colored squares) due to amplification of weak firing
correlations and of shared E or I inputs (Fig. 2F i; Fig. 1F red and green traces). However,
cEI is large and negative due to correlations between E and I cells generated by tracking, leading
to the cancellation:
(3)

(Fig. 2C, filled squares; 2F ii; Fig. S3). Even after this cancellation, however, the instantaneous
current correlation c is still larger than the correlation in firing r (Fig. 2C, filled and open
squares). This is possible because neurons integrate their inputs over time, so that the
instantaneous correlation r is related to the area under the current cross-correlogram (CCG).
Because tracking becomes faster for larger networks, both the width of the current CCG
(effectively set by the EI-Lag) and its magnitude decrease as
(Fig. 2E, insets). Its area
is thus 1/N, as required for asynchronous firing (Fig. 2F iii). Because the asynchronous state
just described is a dynamical phenomenon, it does not require fine-tuning of network
parameters (Fig. S4). Parameter changes lead to adjustments in rates and correlations such the
cancellation in equation 3 still holds.

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While the theory predicts that the population-averaged correlation r should be close to zero,
it does not predict that every pair of cells should be as weakly correlated. Rather, the distribution
of r across pairs is wide, with a standard deviation r much larger than its mean r for large
networks (r decays only as
), resulting in similar numbers of positively and negatively
correlated pairs (Fig. 2G). This is because the hard-wired sources of correlation have a strong
impact on individual rs (of order
) and therefore generate large heterogeneity across
pairs (Fig. S3). Asynchronous activity is also possible under non-stationary conditions:
numerical simulations with time-varying inputs display a similar correlation structure if r is
computed with respect to the time-varying instantaneous average activity of each cell (Fig.
S5).

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Active decorrelation of synaptic currents also occurs in a more biologically plausible network
of spiking neurons. We simulated large networks of randomly connected conductance-based
integrate-and-fire neurons (21), with parameters chosen to produce a balanced state where
neurons fired irregularly (Fig. 3A; shared fraction p = 0.2) (22). As predicted, the distribution
of spike count correlation coefficients r is wide (Fig. 3B), with an extremely low average (in
EE pairs r < 0.001 for all count window sizes, Fig. S6C). This happened for a large range of
average firing rates and connection probabilities (Fig. S7A-F), with synchrony developing only
when inhibition was substantially slower than excitation (Fig. S7G-I). The distribution of r
conditioned on the response to time-varying external inputs was also wide for a large range of
modulation frequencies (Fig. S8). To determine whether a cancellation between the
components of the current correlation (equation 3) underlies the small value of r observed,
we injected different levels of constant current to cell pairs in which we had disabled the spiking
mechanism. The range of current levels was adjusted to isolate the EPSP and the IPSP
components near their respective reversal potentials (23), or combinations of EPSPs and IPSPs
at intermediate potentials. The correlation between isolated EPSPs (Fig. 3C, green) and
between isolated IPSPs (red) was much larger than the correlation measured with no injected
current, due to a cancellation with the large negative correlation between EPSPs and IPSPs
(gold). The V-shape relationship between membrane potential correlation and holding potential
(Fig. 3D) is an experimentally testable prediction of our theory.

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The existence of a wide distribution of spike count correlations was confirmed in neuronal
population recordings collected with silicon microelectrodes in somatosensory and auditory
cortices of urethane-anesthetized rats (21). Under urethane anesthesia, cortical activity displays
spontaneous changes in state (24) homologous to those seen during sleep (25). Network activity
alternates between an activated state of tonic firing resembling REM (ACT; Fig. 4A-B, blue),
and an inactivated state characterized by global fluctuations in population activity (Up-Down
transitions), resembling slow-wave-sleep (InACT; Fig. 4C-D, red). During ACT periods,
correlations were on average remarkably small, and the correlation histogram was wide (Fig.
4B shows one experiment: r = 0.0075; 47% of negatively correlated pairs). These values were
typical of ACT state correlations across different animals (Fig. 4E; n =11 recording sessions
in 9 rats, r median was 0.0053, [0.0024:0.0094] interquartile range; across all 30,772 pairs
r = 0.0052 and 47% had r < 0). This behavior did not depend strongly on the time-scale at
which correlations were measured (Fig. S9). Although r in the ACT state was systematically
very low, it was positive and significantly different from zero in all experiments (Fig. 4E; p <
0.005). A minority of both positive and negative correlations were statistically significant (blue
versus gray in Fig. 4B;Fig. 4F). Pairs with significant and negative (positive) correlations
showed clear troughs (peaks) in their cross-correlograms on average (Fig. 4B, insets; Fig. S10).
Finally, the correlation histogram during the ACT state was still wide even if only neurons
recorded in the same shank were considered (Fig. S11). During InACT periods, as expected
from co-modulation by the slow oscillation, the distribution of r was consistently biased
towards positive values (Fig. 4C-F; n =7 sessions in 5 rats, r median was 0.0953, [0.088:0.109]
interquartile range; across all 18,916 pairs r = 0.096 and 9% had r < 0). Within Up-state
periods, however, average correlations were again very weak (26): removal of Down-states
from the recorded spike trains (21) resulted in correlation histograms very similar to those
during the ACT state (Fig. 4D-E; r median was 0.0163, [0.0066:0.023] interquartile range;
across all 18,916 pairs r = 0.0136 and 45% had r < 0). Thus, correcting for common
modulations in activity induced by the slow oscillation, revealed a wide distribution of
correlations under non-stationary conditions in vivo.

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In summary, we demonstrate theoretically that recurrent network dynamics can lead to an active
decorrelation of synaptic currents, resulting in a state of arbitrarily low mean correlation. We
therefore conclude that shared input does not inevitably cause correlated activity. By
preventing uncontrolled network-wide synchrony, this mechanism generates a background of
weakly correlated spiking, as required for efficient information processing based on either
firing rates or coordinated spike timing patterns (27,28). Both simulations and in vivo
recordings showed a wide distribution of correlations under stationary conditions. In
nonstationary conditions, global activity modulations can result in positively biased
correlations, but correlations around the mean activity imposed by these modulations can still
be extremely small (Fig. 4D-E;Fig. S5 and Fig. S8). Similarly weak correlations have been
reported in visually driven neural populations in area V1 of awake behaving monkeys (29).
However, as the constellation of inputs driving a cortical circuit is in general unknown to the
experimenter, positive correlations may persist even after all experimentally controlled
variables are accounted for (11,12). Whether residual correlations of this nature will have a
strong impact on coding will depend on the extent to which down-stream networks are able to
disambiguate modulations in activity due to different sources. In either case, we suggest that
cortical circuitry does not itself constitute an irreducible source of noise.

Supplementary Material
Refer to Web version on PubMed Central for supplementary material.

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Acknowledgments
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We thank A. Amarasingham, N. Brunel, G. Buzsaki, B. Doiron, A. Ecker, S. Fijisawa, A. Heimel, A. Kohn, D. Robbe,
S. Sakata, E. Stark and A. Tolias for comments on an earlier version of this manuscript, C. van Vreeswijk for discussions
and A. Compte, S. Ardid and J. Manrique for sharing their codes. This study was supported by NIH grants MH073245
and DC009947, NSF grant SBE-0542013 to the TDLC, an NSF Science of Learning Center, an NIDCD grant
DC-005787-01A1 and a Spanish grant FIS 2006-09294. KDH is an Alfred P. Sloan fellow. We would like to dedicate
this work to the memory of D. J. Amit.

References and Notes

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Fig. 1. Effect of shared inputs and correlated inputs on output correlation

(A) Shared excitatory (E, green) or inhibitory (I, red) inputs induce positive correlations in the
synaptic currents of two cells (c > 0). (B) Correlation coefficient of synaptic currents c (dashed)
and output spikes rout (circles, count window T = 50 ms) of a postsynaptic pair of integrateand-fire neurons as a function of the shared input fraction p (21). Each post-synaptic cell
received NE = 250 Poisson input spike trains. (C) Input spike raster (top), synaptic currents
(middle) and membrane potentials (bottom) of a post-synaptic pair receiving weakly correlated
E inputs (black circle in (E), rin = 0.025). (D) Whereas correlations between E inputs or between
I inputs contribute positively to c, correlations between E and I inputs have a decorrelating
effect. (E) Correlations c (dashed) and rout (circles) as a function of the input spike correlation
rin at fixed p = 0.2. E inputs only: each cell receives NE = 250 correlated Poisson spike trains
(21), E and I inputs: NI = 220 inhibitory input trains were added with identical statistics and
correlations. (F) Same as (C) but for the case with E and I inputs (blue circle in (E), rin = 0.025).
E and I currents are shown separately from the total currents (black and gray).

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Fig. 2. Asynchronous activity in a binary recurrent network

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(A) Schematic of the network architecture. The shared input fraction is p. (B) Strong coupling
produces irregular spiking activity due to a dynamic balance between the large excitatory (E
and X) and inhibitory (I) currents to each cell (19,22). Dashed line represents threshold. (C)
Population-averaged correlation coefficients of the firing activity (r, open squares), total
current (c, filled squares) and current components vs. network size N. Dashed lines show
and 1/N scaling for comparison. (D) Instantaneous population-averaged activities
(transformed to z-scores) of the E, I and X neurons, showing that tracking becomes more
accurate with increasing N. Insets show instances of the lag between E and I activities (EILag). Color code as in (B). (E) Population-averaged cross-correlograms (CCGs) of the current
components (N = 8192). Color code as in (C). Insets: magnification of the peak of the IE and
EI CCGs (bottom) shows that the EI-Lag decreases with N, leading to the decrease in the
magnitude and width of the total current CCG (top). (F) Description of the asynchronous selfconsistent solution (see text). (G) The histogram of correlations in the network (EE pairs; N =
8192) is wide: r r.

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Fig. 3. Cancelation of correlations in a recurrent network of spiking neurons

(A) Raster (top) of 500 E (green) and I (red) neurons in a conductance-based integrate-andfire network receiving shared independent Poisson inputs (p = 0.2). Bottom curves show
tracking of instantaneous population-averaged activities (transformed to z-scores, bin size 3
ms). Average firing rate of E and I cells were 1 and 3.6 spike/s, respectively. (B) Histogram
of spike count correlations (black; count window 50 ms) and of jittered spike trains (gray, jitter
500 ms (21)). (C) Population-averaged CCGs of the membrane potential containing mostly
EPSPs (green) or IPSPs (red) in both cells, or EPSPs for one cell and IPSPs for the other (gold).
The black curve is from pairs at resting potential. (D) Peak height of the membrane potential
CCG as a function of the mean holding potential of both neurons in the pair. Green and red
circles correspond the reversal of inhibition and excitation and the black circle corresponds to
rest.

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Fig. 4. Distribution of correlations in the rat neocortex in vivo

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(A) Raster (top) and instantaneous population activity (bottom) for a population of 100
simultaneously recorded neurons (sorted by rate) during a period of cortical activation (ACT).
(B) Histogram of spike count correlations of the population in (A) is wide (r r). The white
curve is the mean histogram of the jittered spike trains (jitter 200 ms, gray shade 95%
confidence interval; count window 50 ms (21)). Insets show average raw cross-correlograms
of all negatively (left) and positively (right) significantly correlated pairs (p < 0.01). (C-D)
Same as (A-B) for the same population of cells during a period of cortical inactivation (InACT).
Histogram of correlations during InACT is biased towards positive values (red). Restricting
the analysis to Up-state activity by removing Down-state periods (black brackets in (C), (21))
largely eliminates the positive bias (Up-St, orange). (E) Box-whisker plots showing the
distribution of mean correlations across experiments for different conditions. Crosses represent
outliers. (F) Median fraction of significantly correlated pairs (p < 0.01, empty bars) and of
significantly and negatively correlated pairs (solid bars) across experiments. Error bars
represent interquartile range.

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