all procedures were approved by the university of texas institutional animal care and use committee and conformed to national institutes of health standards .
three adult male macaque monkeys ( macaca mulatta ) were trained to perform a visual fixation task in which gratings of different orientations were presented .
each trial began when a fixation spot was displayed at the centre of a monitor in front of the monkey .
the monkey had to shift gaze to the fixation point and maintain fixation within a small window ( < 2 full width ) for at least 1500 ms to receive a reward .
a drifting sinusoidal grating was presented at a randomized orientation for 1000 ms while the monkey was maintaining strict fixation , thus minimizing variability due to eye movements .
visual stimuli were presented on a gamma - corrected high - end 21 inch color display ( sony trinitron gdm - f520 ) at a fixed mean luminance of 30 cd / m .
the display subtended 20.5  15.4 at a viewing distance of 108 cm and had a pixel resolution of 1024  768 , 30-bit color depth , and a refresh rate of 100 hz .
visual stimuli were generated using a high - end graphics card on a dedicated pc , using custom - designed software .
behavioral measurements and data acquisition were controlled by a pc running a software package for neurophysiological recordings from alert animals ( reflective computing , st .
recording chambers were located on the dorsal portion of v1 , with the anterior portion of the chamber reaching close to the lunate sulcus and the border between v1 and v2 .
we verified the retinotopic organization by voltage - sensitive dye imaging , and by recording multiunit activity or local field potential with tungsten microelectrodes ( alpha omega co , alpharetta , ga , usa ; microprobes for life sciences , gaithersburg , md , usa ) .
the cortex in our cranial windows represents stimuli that are approximately 2.55 away from the fovea in the lower quadrant of the contralateral hemifield .
as a reference electrode , a silver  silver chloride wire was inserted into the agarose .
the potential of the csf was assumed to be uniform and equal to that of the reference electrode .
pipettes ( 612 m ) were pulled from 1.2 mm outer diameter , 0.70 mm inner diameter kg-33 borosilicate glass capillaries ( king precision glass , claremont , ca , usa ) on a p-2000 micropipette puller ( sutter instruments , novato , ca , usa ) .
patch pipettes were filled with ( in mm ) 135 k - gluconate , 4 nacl , 0.5 egta , 2 mgatp , 10 phosphocreatine disodium , and 10 hepes , ph adjusted to 7.3 with koh ( sigma  aldrich , st .
whole cell current - clamp recordings were performed with an axoclamp 2b microelectrode amplifier ( molecular devices , sunnyvale , ca , usa ) .
we subtracted 7 mv from all raw membrane potential values to compensate for the liquid junction potential .
we analyzed vm during the fixation period in trials on which the monkey performed the task successfully , and provided mean vm in the absence of a visual stimulus was less than 50 mv .
data was analyzed with matlab ( mathworks , natick , ma , usa ) . shot noise contributions to vm were assessed by the skewness of vm distributions .
coherence estimates were performed with chronux , a matlab library freely available from http://chronux.org/. the relationship between spike rate and vm was described with a threshold followed by a power law : r= [ (vmvr ) ] , where (x ) is the heaviside step function , vr is the resting membrane potential , and  is the fitted exponent . orientation selectivity was assessed with an orientation selectivity index ( vector average = 1circular variance ) .
temporal modulation was assessed with the fourier component of the response with the same temporal frequency as the moving sinusoidal grating visual stimulus divided by the time averaged response ( f1/f0 ) .
simulations of hodgkin - huxley neurons used parameters adapted from destexhe et al ( 2001 ) and pospischil et al ( 2008 ) , and were carried out with brian .
we estimated membrane conductance from voltage responses to hyperpolarizing current pulses of constant amplitude , and a fit of a sum of two exponentials to the voltage response : v(t ) = iinj[(rm(1exp(t/m ) ) ) + ( re(1exp(t/e ) ) ) ] , where v is the voltage response , t is time , iinj is injected current , rm is membrane resistance , m is membrane time constant , re is electrode resistance , and e is electrode time constant .
three adult male macaque monkeys ( macaca mulatta ) were trained to perform a visual fixation task in which gratings of different orientations were presented .
each trial began when a fixation spot was displayed at the centre of a monitor in front of the monkey .
the monkey had to shift gaze to the fixation point and maintain fixation within a small window ( < 2 full width ) for at least 1500 ms to receive a reward .
a drifting sinusoidal grating was presented at a randomized orientation for 1000 ms while the monkey was maintaining strict fixation , thus minimizing variability due to eye movements .
visual stimuli were presented on a gamma - corrected high - end 21 inch color display ( sony trinitron gdm - f520 ) at a fixed mean luminance of 30 cd / m .
the display subtended 20.5  15.4 at a viewing distance of 108 cm and had a pixel resolution of 1024  768 , 30-bit color depth , and a refresh rate of 100 hz .
visual stimuli were generated using a high - end graphics card on a dedicated pc , using custom - designed software .
behavioral measurements and data acquisition were controlled by a pc running a software package for neurophysiological recordings from alert animals ( reflective computing , st .
recording chambers were located on the dorsal portion of v1 , with the anterior portion of the chamber reaching close to the lunate sulcus and the border between v1 and v2 .
we verified the retinotopic organization by voltage - sensitive dye imaging , and by recording multiunit activity or local field potential with tungsten microelectrodes ( alpha omega co , alpharetta , ga , usa ; microprobes for life sciences , gaithersburg ,
the cortex in our cranial windows represents stimuli that are approximately 2.55 away from the fovea in the lower quadrant of the contralateral hemifield .
as a reference electrode , a silver  silver chloride wire was inserted into the agarose .
the potential of the csf was assumed to be uniform and equal to that of the reference electrode .
pipettes ( 612 m ) were pulled from 1.2 mm outer diameter , 0.70 mm inner diameter kg-33 borosilicate glass capillaries ( king precision glass , claremont , ca , usa ) on a p-2000 micropipette puller ( sutter instruments , novato , ca , usa ) .
patch pipettes were filled with ( in mm ) 135 k - gluconate , 4 nacl , 0.5 egta , 2 mgatp , 10 phosphocreatine disodium , and 10 hepes , ph adjusted to 7.3 with koh ( sigma  aldrich , st .
whole cell current - clamp recordings were performed with an axoclamp 2b microelectrode amplifier ( molecular devices , sunnyvale , ca , usa ) .
we subtracted 7 mv from all raw membrane potential values to compensate for the liquid junction potential .
we analyzed vm during the fixation period in trials on which the monkey performed the task successfully , and provided mean vm in the absence of a visual stimulus was less than 50 mv .
vm was detrended by high pass filtering at 0.1 hz . data was analyzed with matlab ( mathworks , natick , ma , usa ) . shot noise contributions to vm were assessed by the skewness of vm distributions .
the relationship between spike rate and vm was described with a threshold followed by a power law : r= [ (vmvr ) ] , where (x ) is the heaviside step function , vr is the resting membrane potential , and  is the fitted exponent . orientation selectivity was assessed with an orientation selectivity index ( vector average = 1circular variance ) .
temporal modulation was assessed with the fourier component of the response with the same temporal frequency as the moving sinusoidal grating visual stimulus divided by the time averaged response ( f1/f0 ) .
simulations of hodgkin - huxley neurons used parameters adapted from destexhe et al ( 2001 ) and pospischil et al ( 2008 ) , and were carried out with brian .
we estimated membrane conductance from voltage responses to hyperpolarizing current pulses of constant amplitude , and a fit of a sum of two exponentials to the voltage response : v(t ) = iinj[(rm(1exp(t/m ) ) ) + ( re(1exp(t/e ) ) ) ] , where v is the voltage response , t is time , iinj is injected current , rm is membrane resistance , m is membrane time constant , re is electrode resistance , and e is electrode time constant .
 in the mammalian cerebral cortex , neural responses are highly variable during spontaneous activity and sensory stimulation . to explain this variability , 
 the cortex of alert animals has been hypothesized to be in an asynchronous high conductance state in which irregular spiking arises from the convergence of large numbers of uncorrelated excitatory and inhibitory inputs onto individual neurons14 . 
 signatures of this state are that a neuron s membrane potential ( vm ) hovers just below spike threshold , and its aggregate synaptic input is nearly gaussian , arising from many uncorrelated inputs14 . 
 alternatively , irregular spiking could arise from infrequent correlated input events that elicit large vm fluctuations5,6 . to distinguish these hypotheses 
 , we developed a technique to carry out whole - cell vm measurements from the cortex of behaving monkeys , focusing on primary visual cortex ( v1 ) of monkeys performing a visual fixation task . 
 contrary to the predictions of an asynchronous state , mean vm during fixation was far from threshold ( 14 mv ) and spiking was triggered by occasional large spontaneous fluctuations . 
 distributions of vm values were skewed beyond that expected for a range of gaussian input6,7 , but were consistent with synaptic input arising from infrequent correlated events5,6 . 
 furthermore , spontaneous vm fluctuations were correlated with the surrounding network activity , as reflected in simultaneously recorded nearby local field potential ( lfp ) . 
 visual stimulation , however , led to responses more consistent with an asynchronous state : mean vm approached threshold , fluctuations became more gaussian , and correlations between single neurons and the surrounding network were disrupted . 
 these observations demonstrate that sensory drive can shift a common cortical circuitry from a synchronous to an asynchronous state . 
ONLINE METHODS
Behavioral task and visual stimulus
Whole cell recordings
Data Analysis
Data Analysis for 
Supplementary Material