an animal s reaction to a sensory stimulus depends on the context in which it is presented . in the cortex ,
even primary sensory areas receive a large number of  top - down  inputs from higher - order regions , in addition to the thalamic input  that directly conveys sensory messages .
these top - down connections are believed to underlie the integration of sensory inputs with nonsensory context .
one case in which a role for top - down cortical connections has been established is attention in the primate visual system .
strong electrical stimulation of the frontal eye fields ( fefs ) produces eye movements to a topographically aligned location in space .
however , weaker electrical stimulation  below the threshold for eliciting an overt saccade  instead mimics the effects of attention to this location , causing increased behavioral and neuronal responses to stimuli presented there ( moore and armstrong , 2003 ) . in rodents , a robust experimental model of attention has not yet been established . however , there are remarkable parallels between the effects of attention on cortical processing in primates and changes in cortical state that occur with changes in behavioral context in rodents ( harris and thiele , 2011 ) .
cortical states were first described in relation to the sleep cycle . during slow - wave sleep , animals exhibit a synchronized state , characterized by large , slow fluctuations in the spiking and membrane potentials of large neuronal populations . by contrast , the cortex of awake , active , and alert animals exhibits a desynchronized state ( also termed activated state ) in which slow fluctuations are replaced by tonic cortical firing , often together with a higher - frequency gamma oscillation .
recent work has shown that these classical states are in fact points on a continuum .
for example , quietly resting rodents show a  moderately synchronized state , with fluctuations in cortical activity that are shallower and faster than classical sleep oscillations . when animals engage in active behaviors such as whisking or running , however , these moderate fluctuations are further reduced ( polack et  al . , 2013 ; poulet et  al . ,
there are several parallels between the correlates of selective attention in primates and cortical states in rodents .
their effects on local field potential oscillations are similar : when animals pay attention to a particular location in space , low - frequency oscillations are reduced in the aligned region of area v4 , while high - frequency lfps are increased ( fries et  al . , 2001 ) . attention and desynchronization
both produce a decrease in trial - to - trial variability and noise correlation of sensory responses ( cohen and maunsell , 2011 ; goard and dan , 2009 ; marguet and harris , 2011 ; mitchell et  al . ,
importantly , these effects only occur when attention is directed into the receptive fields of recorded neurons .
this suggests that attention causes an effect similar to desynchronization , occurring locally in the region of visual cortex topographically aligned with the attended location .
moreover , recent results suggest that when attention is directed not to a region of space but to a visual feature , variability and correlation decrease in the population that encodes this feature ( cohen and maunsell , 2011 ) , suggesting that a phenomenon analogous to desynchronization has occurred in a spatially distributed neuronal assembly . the mechanisms of cortical state change have been a subject of investigation for many decades .
the first , espoused by steriade and colleagues , held that cortical states are modulated primarily via the thalamus . in this view , increased cholinergic input to thalamic relay cells leads to increased tonic firing and thus to a steady glutamatergic drive to cortex that causes desynchronization .
the second perspective , espoused by vanderwolf and colleagues , held that cortical state reflected direct neuromodulation of neocortex .
recent research provides support for both mechanisms . in the rodent somatosensory system , whisking causes increased tonic firing in thalamus ; blocking thalamic firing with muscimol reduces the cortical depolarization caused by whisking , whereas stimulating thalamus optogenetically causes cortical desynchronization ( poulet et  al . , 2012 ) .
support for direct cortical neuromodulation comes from the ability of locally applied neuromodulatory blockers to reduce the desynchronization caused by electrical stimulation of nucleus basalis or locomotion ( goard and dan , 2009 ; polack et  al . ,
if attention does indeed consist of cortical state change occurring at a local  level , one might expect the two phenomena to have similar circuit mechanisms .
in particular , given the role of top - down cortical connections in attention , it has been hypothesized that tonic glutamatergic input from higher - order cortex should also cause desynchronization in rodent cortex ( harris and thiele , 2011 ) .
( 2013 ) performed a number of elegant experiments to study the role of  top - down connections from vibrissa motor cortex ( vm1 ) to barrel cortex ( s1 ) .
they found that blocking spiking in vm1 using muscimol shifted s1 toward more synchronized states , whereas optogenetically increasing vm1 activity shifted s1 toward more desynchronized states .
importantly , the effects on s1 state did not simply reflect the consequence of these manipulations on behavior .
as might be expected , suppression or activation of vm1 activity caused a corresponding decrease or increase in the probability and amplitude of whisking .
nevertheless , an effect of manipulating vm1 on s1 state was seen even when analyzing data within whisking or nonwhisking periods .
one can thus make an analogy between the effects of stimulating vm1 in rodents and the effects of stimulating fef in primates : while strong enough stimulation of these areas causes an overt movement ( saccade or whisking ) , weaker stimulation may instead produce covert effects on sensory processing in lower cortical areas ( attention or desynchronization ) . to investigate the mechanisms by which vm1 stimulation causes desynchronization of s1 , zagha et  al .
current - source density analysis showed that vm1 stimulation produces sinks in layer 1 and layers 5/6 , corresponding to the major termination zones of these cortical feedback axons . by applying varying concentrations of the glutamatergic antagonist cnqx
, they showed that the increase in firing of superficial layer s1 neurons required layer 1 inputs , whereas inputs terminating in deep layers were sufficient for increased firing of layer 5 cells . to investigate whether stimulation of vm1 desynchronizes s1 via a direct pathway , without requiring additional relay stations , they performed additional tests .
optogenetic activation of vm1 could still desynchronize vs1 after suppressing activity in vpm thalamus ; and optical stimulation of vm1 axons in s1 could still activate s1 even when the firing of vm1 somas was blocked to eliminate antidromic signaling .
these data confirm that , in addition to the classical pathways that modulate cortical states , top - down projections are capable of directly desynchronizing sensory cortex ( see figure  1 ) .
previous work has shown that the response to strong , sudden stimuli , such as tone onsets or whisker deflections is robust in both synchronized and desynchronized states ( castro - alamancos , 2004 ; luczak et  al . , 2013 ) .
however , more subtle , temporally extended stimuli such as natural movies , sustained tones , or repeated whisker deflections are represented more faithfully by the desynchronized cortex ( goard and dan , 2009 ; luczak et  al
one may again make an analogy with attention : strong , sudden stimuli which are capable of eliciting  bottom - up 
attention are able to drive responses in either state , but  faithful representation of weaker stimuli requires  top - down  attention in the form of cortical desynchronization .
( 2013 ) investigated the effects of vm1-elicited desynchronization on the representation of a sequence of whisker deflections of random amplitudes .
consistent with this view , they found that the representation of low - amplitude whisker deflections was made more reliable by vm1 stimulation , but the representation of large - amplitude deflections was less affected .
this study has provided very important information on the function of top - down connections in rodent cortex , as well as further support for a close relationship between cortical state modulation and selective attention .
first , how specifically can top - down connections modulate sensory cortex in rodents ? in primates , selective attention causes effects analogous to desynchronization in localized areas of cortex and even in anatomically distributed neuronal assemblies ( cohen and maunsell , 2011 ; fries et  al .
stimulation of primate fef causes increased sensory responses and reduced variability only in topographically aligned regions of v4 ( moore and armstrong , 2003 ) .
( 2013 ) provide a partial answer to this question by showing that vm1 stimulation causes less desynchronization of visual cortex than of barrel cortex . but
could projections from vm1 to vs1 selectively target a single whisker barrel or a distributed neuronal assembly ?
( 2013 ) s study , together with previous work , shows that there are at least three circuit pathways that can contribute to cortical desynchronization : direct neuromodulation of cortex , increased tonic activity of thalamus , and increased corticocortical input ( see figure  1 ) .
there are reasons to suspect that the space of states is indeed multidimensional , i.e. , that in addition to the common effect of reducing low - frequency fluctuations , different desynchronizing manipulations have diverse effects on cortical processing .
2013 ) showed that strong vm1 stimulation typically increases the firing rates of both of superficial and deep layer neurons .
a similar effect was seen due to running in mouse v1 ( niell and stryker , 2010 ) , but desynchronizing brainstem stimulation ( sakata and harris , 2012 ) , or  direct cholinergic manipulation of thalamus ( hirata and castro - alamancos , 2010 ) , causes a desynchronization with suppressed superficial layer firing .
together with other examples ( harris and thiele , 2011 ) , these results suggest that the different pathways mediating cortical desynchronization have nonidentical effects on cortical processing .
given the number of ways that context can affect stimulus perception , one should expect the neural circuits producing nonsensory control of cortex to be highly complex .
 sensory cortices receive inputs not only from thalamus but also from higher - order cortical regions . here , zagha et  al . 
 ( 2013 ) show that motor cortical inputs can switch barrel cortex into a desynchronized state that enables more faithful representation of subtle sensory stimuli . 
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