the mammalian auditory system is challenged with the task of accurately encoding the pattern and source of incoming sound . many of the initial steps involved in the manipulation of acoustic information already have been well - characterized ( webster , 1992 ; winer , 2005 ) . in the standard model , auditory information is first transmitted from the cochlea ( ryugo , 1992 ) to the cochlear nucleus ( ca nt , 1992 ) , where it is distributed across multiple parallel ascending streams to the superior olivary complex , the lateral lemniscal nuclei ( schwartz , 1992 ) , and the inferior colliculus ( ic ) ( oliver and huerta , 1992 ) . subsequently , information is communicated to the medial geniculate body ( mgb ) of the thalamus ( winer , 1992 ) , where it is then transferred to the primary auditory cortex and on to higher auditory cortical areas ( kaas and hackett , 2000 ; lee and winer , 2008b ) . the tonotopic organization of frequency -- specific channels established at the cochlea is one of the few organizing features that persist throughout the auditory pathway ( kandler et al . , 2009 ) . in the classical view , the principle route for -auditory information traverses through these tonotopic nuclei at each level of processing . however , numerous parallel ascending ( winer , 2005 ) and descending ( winer , 2006 ) pathways complicate this simple picture , and their roles in audition have yet to be adequately elucidated . for example , the ascending pathways through the non - tonotopically organized nuclei and the large number of descending projections pose unanswered questions regarding their roles in auditory information processing . assessing the putative functions of such projections has been recently aided by anatomical and physiological findings that segregate the main glutamatergic pathways into two types ( sherman and guillery , 1998 ) ( figure 1 ) . the first type termed drivers are similar to the potent retinogeniculate projections in the visual system , and are likely the main conduits for the transmission of auditory information ( reichova and sherman , 2004 ; sherman and guillery , 2006 ; lee and sherman , 2008 , 2010 ) . in contrast , the second type termed modulators have vastly -different properties , and may instead modify the main information - bearing streams ( reichova and sherman , 2004 ; sherman and guillery , 2006 ; lee and sherman , 2009b ) . we have used these properties to characterize several pathways in the central stages of auditory processing , and to identify the likely routes for auditory information flow from the ic through thalamus to the auditory cortex ( lee and sherman , 2008 , 2009b , 2010 ; llano and sherman , 2008 ) . here we review these recent findings , the open questions , and the future directions . summary of anatomical and physiological properties of driver ( red ) and modulator ( green ) synapses onto a neuron ( blue ) ( adapted from lee and sherman , 2009b ) . assessing the information - bearing role of the central auditory pathways is an important challenge , but it is one that can be addressed partly using anatomical and physiological criteria ( figure 1 ) . as mentioned above , glutamatergic synapses can be characterized as either drivers or modulators of activity . driver pathways are suggested to be the principal conduits for information flow , while modulator pathways modify these main information - bearing streams . such a characterization has been derived from previous work , mostly in mice and cats , on the retinogeniculate and corticothalamic ( ct ) projections in the visual and somatosensory systems ( li et al . , 2003 ; reichova and sherman , 2004 ) , and this has been extended across multiple synapses in the auditory system ( winer et al . , 1999 ; huang and winer , 2000 ; bartlett and smith , 2002 ; lee and sherman , 2008 , 2009b , 2010 ; llano and sherman , 2008 ) . the distinction between the two types of input derives in part from morphological observations of axonal arborizations . driver input often resembles that of the retinal input to the lateral geniculate nucleus ( lgn ) , which has been termed type 2 morphology by guillery ( 1966 ) . this morphological type has thick axons , dense terminal arbors ( guillery , 1966 ; ralston , 1971 ; famiglietti and peters , 1972 ) , and large endings that contact the proximal dendrites of relay cells ( winer et al . , 1999 ; llano and sherman , 2008 ) , often in triadic structures in glomeruli ( ralston , 1971 ; famiglietti and peters , 1972 ; hamos et al . , 1987 ) . like the retinal driver inputs , the driver projections produce large , all - or - none epsps by activating only ionotropic glutamate receptors ( iglurs ) , and they exhibit synaptic depression ( bartlett and smith , 2002 ; li et al . , 2003 ; in contrast , glutamatergic modulator inputs have different morphologies , called type 1 by guillery ( 1966 ) and exemplified by the corticogeniculate feedback pathway from layer 6 of visual cortex . this morphological type has thin axons , sparse arbors , and small terminals ending on distal dendrites ( sherman and guillery , 2006 ) . their physiological properties differ as well , exhibiting synaptic facilitation and producing small , graded epsps by engaging both iglurs and metabotropic glutamate receptors ( mglurs ) ( bartlett and smith , 2002 ; li et al . , 2003 ; reichova and sherman , 2004 ) ( figure 1 ) . these glutamatergic modulators should not be confused with the various neuromodulator pathways , such as those using acetylcholine ( varela and sherman , 2007 ) and serotonin ( varela and sherman , 2009 ) as neurotransmitters ; their synaptic properties and roles may be very different . these properties likely support the roles of driver and modulator pathways in information processing . thus , driver synapses are likely highly - reliable and efficient transmitters of information , given their close proximity to the neuronal cell body and their high probability of transmitter release ( gil et al . , 1999 ; furthermore , the synaptic depression has been suggested to act as a dynamic gain control mechanism specific to the input , which is very useful in information flow as firing rates of the afferents change ( abbott et al . , 1997 ) . modulator projections , with their distal dendritic locations , lower probability of transmitter release , and prolonged responses from mglurs , are less suited as conveyors of information ( stratford et al . , 1996 ; gil et al . , 1999 ; sherman and guillery , 2006 ) . however , the prolonged responses afforded by activation of mglurs not only modulates such properties as overall excitability , but also -provides control of many time- and voltage - gated ion channels in the target cell , a feature that is poorly controlled by driver inputs with their brief epsps ( sherman and guillery , 2006 ) ; such prolonged mglur responses would also act like low - pass temporal filters , resulting in less information transferred across the synapse ( sherman and guillery , 2006 ) . these multiple anatomical and physiological criteria for distinguishing glutamatergic synapses have been useful for characterizing the auditory pathways from the ic , thalamus and cortex ( lee and sherman , 2008 , 2009b , 2010 ; llano and sherman , 2008 ) , which we review below . these properties also provide the foundation for ongoing and future investigations of the information - bearing roles of the intracortical and corticocortical connections in the various auditory cortical areas . the driver and modulator framework has been particularly useful in the delineation of forebrain sensory pathways , particularly in the parcellation of thalamic relays , which can be classified as either a first order nucleus ( fo ) or higher order nucleus(ho ) ( sherman and guillery , 2002 , 2006 ) , based on the source of their driving input . fo nuclei , such as the lgn , ventral division of the medial geniculate body ( mgbv ) and ventroposterior medial nucleus ( vpm ) , receive their principal driving input from peripheral sources , while ho nuclei , such as the pulvinar ( lp - pul ) , dorsal division of the mgb ( mgbd ) , and posteromedial nucleus ( pom ) , receive their driving input mainly from layer 5 of the cortex ( figure 2 ) . note that both fo and ho thalamic nuclei receive feedback modulatory input from cortical layer 6 , but only ho nuclei , in addition , receive a feedforward driver input from cortical layer 5 . interestingly , this suggests that the ho thalamic relays transmit layer 5 driver input from one cortical area to the thalamic recipient layers of a second cortical area ( sherman and guillery , 2002 ; reichova and sherman , 2004 ; lee and sherman , 2008 ) , analogous to the fo transmission by the lgn of retinal input to the primary visual cortex ( figure 2 ) , and likewise may utilize the unique operational modes of the thalamus , including gating and the different burst versus tonic firing modes of relay cells ( cox et al . , 1998 ; these distinctions between fo and ho pathways have particular relevance for the central auditory pathways , as we discuss below . model of auditory information flow from the inferior colliculus ( ic ) , medial geniculate body ( mgb ) and auditory cortex ( ai , aii ) . driver inputs ( red ) are the main information - bearing pathways , while modulator inputs ( green ) modify the information being transmitted ( adapted from lee and sherman , 2010 ) . among the main auditory centers , the ic is particularly salient as the site of convergence from downstream sources in the cochlear nucleus , superior olivary complex and the lateral lemniscal nuclei , as well as feedback projections from the auditory cortex ( oliver and huerta , 1992 ) , and thus represents a major hub for integrating ascending and descending processing streams . the central nucleus of the inferior colliculus ( icc ) is the main tonotopically organized subdivision ( romand and ehret , 1990 ; malmierca et al . , 2008 ) , and is the principal source of information ascending to the mgbv ( winer , 2005 ) . surrounding the icc are the lateral ( icl ) , dorsal ( icd ) , and caudal cortices of the ic ( icca ) , which we collectively refer to as the shell regions ( ics ) . these subdivisions are primarily non - tonotopically organized ( romand and ehret , 1990 ; malmierca et al . , 2008 ) , and project to the mgbd and medial ( mgbm ) divisions of the mgb ( wenstrup , 2005 ) . interestingly , the role of these non - lemniscal projections to the mgb are not well - defined ( hu , 2003 ; wenstrup , 2005 ) . previous models have suggested that the ascending tectothalamic pathways from the icc and ics to the mgbv , mgbd and mgbm , respectively , represent parallel paths for the flow of auditory information ( hu et al . , 1994 ; hu , 2003 ; wenstrup , 2005 ) . these data demonstrate that the tectothalamic synapse from the icc exhibits properties associated with driver synapses ( bartlett and smith , 2002 ; lee and sherman , 2010 ) , while the ics projection instead has modulator characteristics ( bartlett and smith , 2002 ; smith et al . , 2007 ; lee and sherman , 2010 ) ( table 1 ) . thus , in the alternative model of auditory tectothalamic transmission , the main information - bearing pathway is proposed to arise primarily from the icc , while the pathway from the ics instead modulates information flow through the higher order auditory thalamus ( figure 2 ) ( bartlett and smith , 2002 ; smith et al . , 2007 ; lee and sherman , 2010 ) . interestingly , the source of the driving inputs to the higher order auditory thalamic nuclei instead arises from layer 5 of the primary auditory cortex ( see above ) ( figure 2 ) ( bartlett and smith , 2002 ; llano and sherman , 2008 ) . thus , the tectothalamic projection from ics should act to modulate the corticothalamocortical processing stream through the higher order auditory thalamus ( sherman and guillery , 2006 ; lee and sherman , 2010 ) . information ascending to the auditory cortex must first be conveyed through the mgb of the thalamus , yet the importance of the mgb in audition extends beyond a role as merely a relay ( sherman and guillery , 2006 ; lee and sherman , 2008 ; lee and winer , 2008a ) . of the main mgb nuclei , the mgbv is the primary conduit for tonotopic information ascending to the primary auditory cortex , whereas the mgbd and mgbm divisions are not tonotopically organized and project broadly to non - tonotopic , multimodal and limbic related areas ( kaas and hackett , 2000 ; lee and winer , 2008a ; llano and sherman , 2008 ) . the mgb also receives major projections from layers 5 and 6 of the auditory cortex ( winer et al . , 2001 ; llano and sherman , 2008 ) , which either transmit or modulate information through the thalamus ( see below ) ( figure 2 ) . the thalamocortical projections from the non - tonotopic nuclei of the mgb have been presumed to perform alternative functions , such as regulating attention ( olshausen et al . , 1993 ) , and this view is challenged by findings that demonstrate anatomical and physiological similarity among the thalamocortical projections from the mgbv and mgbd ( huang and winer , 2000 ; rose and metherate , 2001 ; llano and sherman , 2008 ; lee and sherman , 2009b ) . morphologically , these thalamocortical projections have large , dense , bushy arborizations in layer 4 that extend into layer 3 ( huang and winer , 2000 ; llano and sherman , 2008 ) . physiologically , these projections demonstrate large epsps that depress in response to paired - pulse stimulation and lack a metabotropic glutamate component ( rose and metherate , 2001 ; lee and sherman , 2009b ) . thus , projections from both the mgbv and mgbd share driver - like properties ( table 1 ) , and suggest that the projections from the mgbd have a role similar to that of the mgbv , i.e. , as an -information - bearing pathway to the higher auditory cortical areas ( figure 2 ) . the main distinction between them is that mgbv is an fo relay , while mgbd is an ho relay ( see above ) . an interesting question remaining concerns the thalamocortical projections to layer 1 from the mgbm ( huang and winer , 2000 ; jones , 2009 ) , part of the  matrix  system defined by jones ( 2009 ) , whose role remains to be defined . thus , although it is generally regarded simply a relay of ascending auditory information , the mgb has important roles ranging from the transformation of auditory information ( miller et al . , 2001 ) to continuing the flow of intraareal processing in the cortex ( see below ) ( sherman and guillery , 2006 ; lee and sherman , 2008 ) . the auditory cortex is the ultimate target for information ascending from the periphery through the mgb ( lee and winer , 2008a , b ; llano and sherman , 2008 ) . similar to lower -stations , tonotopy is an organizing feature of the primary auditory cortex ( ai ) , but is absent in the surrounding non - tonotopic and multimodal areas , such as the secondary auditory area ( aii ) ( stiebler et al . , 1997 ; kaas and hackett , 2000 ; lee et al . , 2004 ) . the size and number of these auditory cortical areas varies among species , e.g. , there are two tonotopic areas in the mouse ( stiebler et al . , 1997 ) , three in the monkey ( hackett et al . , 1998 ) and five in the cat ( reale and imig , 1980 ) . yet , an unresolved issue is : how do these multiple areas interact to compute features in the auditory scene ? in the standard hierarchical cortical model of auditory processing , information is sent progressively via direct corticocortical connections from lower auditory areas , such as ai , to higher auditory areas , such as aii ( felleman and van essen , 1991 ; rouiller et al . , 1991 ) . such successive convergence of auditory inputs purportedly accounts for the increasingly complicated receptive fields of higher auditory areas , such as aii ( schreiner and cynader , 1984 ) . interestingly , the synaptic properties of these direct corticocortical connections have not been examined until recently ( covic et al . , 2009 ) , and their salience is questionable , given recent findings that suggest an alternate route for interareal processing via a corticothalamocortical route ( figure 2 ) ( reichova and sherman , 2004 ; sherman and guillery , 2006 ; lee and sherman , 2008 ; llano and sherman , 2008 ; theyel et al . , the alternate corticothalamocortical route for interareal auditory processing is enabled by driver projections that originate from layer 5 of the primary auditory cortex and synapses in the higher order auditory thalamus , i.e. , mgbd ( table 1 ) ( ojima , 1994 ; winer et al . , 1999 ; these feedforward ct projections are distinguished from the feedback layer 6 projections , which exhibit modulator characteristics and project to the originating thalamic nucleus , e.g. , ai to mgbv ( table 1 ) ( ojima , 1994 ; bartlett et al . , 2000 ; thus , the ai layer 5 inputs to mgbd , in conjunction with the driver thalamocortical projections from mgbd to aii ( see above ) , establish a transthalamic route for the interareal transfer of auditory information ( figure 2 ) . this alternate route does not negate the potential information - bearing roles of the direct corticocortical projections ( rockland and pandya , 1979 ; lee and winer , 2008b ) , which are composed of an intricate pattern of laminar - specific driver and modulator projections ( covic et al . , 2009 ) . thus , auditory forebrain computations involve multiple processes beyond those suggested by simple -cortical hierarchies ( felleman and van essen , 1991 ; rouiller et al . , 1991 ) . finally , intrinsic cortical microcircuits further transform auditory information before redistribution through the cortical network ( feldmeyer and sakmann , 2000 ; silberberg et al . , 2004 ; this issue is complicated by the complexity and floridness of intrinsic cortical interconnections , which account for almost half of the input to a cortical column ( ahmed et al . , 1994 ; one potential driving circuit extends from layer 4 to layers 2/3 and then to layer 5 ( hirsch and martinez , 2006b ; lee and sherman , 2009a ) , and then outputs to the higher order thalamus ( ojima , 1994 ; winer et al . , 1999 ; llano and sherman , 2008 ) , but the bulk of intrinsic connections may be instead more likely to exhibit modulator properties , such as the layer 6 to layer 4 projections ( ahmed et al . , 1994 ; stratford et al . , 1996 ; prieto and winer , 1999 ; tarczy - hornoch et al . , 1999 ; lee and sherman , 2008 , 2009b ) . in this manner , functional connectivity within the auditory cortex may resemble that in the thalamus , where synaptic weight is inversely proportional to anatomical weight ( binzegger et al . the driver and modulator framework adds a unique perspective to our ongoing understanding of the central auditory pathways . as such , these properties may fruitfully be applied to other pathways of interest throughout the auditory system , such as the thalamoamygdaloid pathway ( doron and ledoux , 1999 ) . however , for instance , how do driver and modulator pathways interact functionally to construct auditory receptive fields ? , how do these properties extend across systems and species ? indeed , the utility of this framework is not constrained to the auditory modality , as its relevance in other sensory systems has already been established ( reichova and sherman , 2004 ; petrof and sherman , 2009 ) , but has not yet been extended to non - mammalian species . in this respect , a comparative approach that extends the investigation of these properties in other organisms may lend unique insights into the ontogeny , development and evolution of the sensory pathways in higher organisms . the authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest .
the classic view of auditory information flow depicts a simple serial route from the periphery through tonotopically - organized nuclei in the brainstem , midbrain and thalamus , ascending eventually to the neocortex . yet , complicating this picture are numerous parallel ascending and descending pathways , whose roles in auditory processing are poorly defined . to address this ambiguity , 
 we have identified several anatomical and physiological properties that distinguish the auditory glutamatergic pathways into two groups that we have termed  drivers  and  modulators  . 
 driver pathways are associated with information - bearing pathways , while modulator pathways modify these principal information streams . 
 these properties illuminate the potential roles of some previously ill - defined auditory pathways , and may be extended further to categorize either unknown or mischaracterized pathways throughout the auditory system .