The corticothalamocortical circuit drives higher-order cortex in the mouse

“However, a recent hypothesis suggests that much, and perhaps the vast majority of, information flow between cortical areas involves higher-order thalamic nuclei in the form of corticothalamocortical circuit”

“This latter hypothesis is based partly on the idea that many brain circuits can be divided into 'drivers', which represent the main information routes, and 'modulators', which serve to modulate information flo”

“A major difference between these routes might be related to the observation that, although essentially all direct corticocortical projections lie strictly in cortex, the corticothalamocortical pathway emanates from layer 5B cells, most or all of which have axons that branch to innervate thalamus and other subcortical…”

“Well-documented examples of drivers are the retinal input to the lateral geniculate nucleus or lemniscal input to the ventral posterior nucleus; modulator examples are feedback layer 6 corticothalamic projections and cholinergic brainstem inputs to thalamu”

“Well-documented examples of drivers are the retinal input to the lateral geniculate nucleus or lemniscal input to the ventral posterior nucleus; modulator examples are feedback layer 6 corticothalamic projections and cholinergic brainstem inputs to thalamu”

“The relevant structures in the slice include S1BF, secondary somatosensory cortex, posterior medial nucleus of the thalamus (POm), and the connections between S1BF/POm and secondary somatosensory cortex/PO”

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“, higher-order thalamic receptive-field dependency on cortical input”

“Thus, this arm of information transfer reflects output that is sent to both cortical and extrathalamic subcortical motor targets, implying that this circuit, by having a large effect on its cortical target, may be an effective monitor of motor control signal”

“The relevant structures in the slice include S1BF, secondary somatosensory cortex, posterior medial nucleus of the thalamus (POm), and the connections between S1BF/POm and secondary somatosensory cortex/PO”

“A major difference between these routes might be related to the observation that, although essentially all direct corticocortical projections lie strictly in cortex, the corticothalamocortical pathway emanates from layer 5B cells, most or all of which have axons that branch to innervate thalamus and other subcortical…”

“and nonreciprocal corticothalamocortical organization for layer 5B, but not layer 6, corticothalamic output”

“The relevant structures in the slice include S1BF, secondary somatosensory cortex, posterior medial nucleus of the thalamus (POm), and the connections between S1BF/POm and secondary somatosensory cortex/PO”

“The strongest evidence for this claim comes from the somatosensory system, where it was shown recently that the posterior medial nucleus of the thalamus (POm) – a higher-order thalamic nucleus that receives direct input from cortex – can relay information between S1 and S2 (Theyel et al., 2009).”

“For example, the posterior nucleus transfers information from primary area to secondary somatosensory areas (Theyel et al., 2010).”

“In vitro studies have shown that microstimulation of the indirect pathways strongly activated cortical areas (Theyel et al., 2010).”

“[75], “corticothalamocortical information transfer may represent an important addition to, or even replacement of, the current dogma that corticocortical transfer of primary information exclusively involves direct corticocortical pathways.”

“In this way, pathologic BG output may block effective cortico-thalamo-cortical communication [30].”

“Nonspecific thalamic systems receive inputs from layer 5 (Jones, 2001; Theyel et al., 2010), contain multisensory neurons (Avanzini et al., 1980) and senddiffuse axonal projections to supragranular layers, irrespective of cortical boundaries (Jones, 2001).”

“Such a cortex-thalamus-cortex pathway could be consistent with either a role in attention or in the relay of sensory information from one area to another (Purushothaman et al., 2012; Sherman, 2007; Theyel et al., 2010).”

“In vitro studies clearly show that direct cortico-cortical as well as cortico-thalamic projections may contribute in specific ways (Theyel et al., 2010; Adesnik and Scanziani, 2010).”

“Although the underlying mechanism is unclear, recent evidence suggests that higher-order thalamic lesions perturb cortico-cortical information transmission (Theyel et al., 2010; Purushothaman et al., 2012).”

“…L5B pyramidal cells result in the efficient recruitment of POm relay neurons (via their giant presynaptic terminals; Groh et al., 2008) which in turn activate L4 neurons in the higher-order S2 cortex (Carvell and Simons, 1987; Spreafico et al., 1987; Alloway et al., 2000; Theyel et al., 2010).”

“…al. (2003, 2005 (2009), Bureau et al. (2004, 2008), Zhao et al. (2009), Lam and Sherman (2005, 2007, 2010), Lam et al. (2006), Lee and Sherman 2009a,b, 2010), Wood and Shepherd (2010) In vivo laser scanning microstimulation mapping Komiyama et al. (2010) to write user functions and how to create…”

“The thalamus is not merely a relay station for sensory input and motor control, it is also crucially involved in the interconnections between higher-order somatosensory cortices (Theyel et al., 2010).”

“…extralemniscal pathway through VPMvl (Pierret et al., 2000; Bokor et al., 2008), but also via Pom (Carvell and Simons, 1987; Spreafico et al., 1987; Alloway et al., 2000; Theyel et al., 2010) and from both the barrel and septal columns of wS1 (Kim and Ebner, 1999; Chakrabarti and Alloway, 2006).”

“Higher-order thalamic nuclei are often envisioned to relay information between cortical regions (Sherman, 2016; Theyel et al., 2010).”

“Another possibility is that subcortical structures such as the thalamus or the superior colliculus play a greater role than previously thought in defining the flow of information between cortical regions (28, 29).”

“(Theyel et al. 2010; Sherman, 2017) situated at the nexus of the mPFC and HC.”

“The wiring and functional properties of other TC neuron types remain at present poorly understood (Theyel et al., 2010).”

“In contrast, there is very little age-dependent change in the power of centroparietal (fast) spindles across this same developmental period [118].”

“This contrasts with S1 barrels, where VPM and PO axons target L4 and L5A, respectively (Feldmeyer, 2012), but is consistent with previous findings of PO input to neurons in L4 of S2 (Herkenham, 1980; Theyel et al., 2010; Pouchelon et al., 2014) and inter-barrel septa in L4 of rat S1.”

“Having described the nature and origin of globularity, as well as the limits of hypotheses based on laterality and brain size, we are now in a position to formulate our hypothesis, which is to link globularity with the language-ready brain.”

“…of the subcortical nuclei that includes the MGB and IC would likely influence the transfer of ascending input to the AC (Villa et al., 1991; Luo et al., 2008), as well as the corticocortical processing itself, as demonstrated in other sensory systems (Sillito et al., 2006; Theyel et al., 2010).”

“Implicit in this concept is the idea that these transthalamic circuits are feed forward, such as from S1 to S2, and there is indeed evidence for this (38).”

“The posterior Neuron 92, November 23, 2016 697 nucleus provides strong excitation to the input layers of the secondary somatosensory cortex (Lee and Sherman, 2008; Theyel et al., 2010).”

“Higher-order nuclei may relay internal information between cortical areas (Theyel et al., 2010) or, as is the focus here, from subcortical areas to cortex.”

“It is not clear whether this observation also relates to a decrease in cortico-thalamocortical coupling, as disconnection of the thalamus from the functional brain graph may not only prohibit flow of ascending information to the cortex, but also alter integration of information between cortical areas (Theyel et al., 2…”

“higher order thalamic relay to another cortical area [10 ,12,13].”

“Although ChR2 stimulation revealed the expected intracortical activation patterns, the responses may also reflect activity within more complex pathways through the thalamus (Theyel et al., 2010) or brainstem (Nguyen and Kleinfeld, 2005; Matyas et al., 2010).”

“…innervations from the cortex to the thalamus send critical feedback to modulate the thalamic responses required to perform the complex information processing and integration that underlie cognitive behaviors (Jones, 2002; Alitto & Usrey, 2003; Temereanca & Simons, 2004; Theyel et al., 2010).”

“…cortico-thalamo-cortical feedback loops, which would complicate interpretation of the results as a purely cortical phenomenon [see the studies by Theyel et al. (2010) and Golshani et al. (2001) for cortico-thalamo-cortical connectivity in mouse slices; see also Rigas and Castro-Alamancos…”

“These results are consistent with an active computational role of thalamus in sensory-motor processing (Theyel et al., 2010; Hooks et al., 2013; Petrus et al., 2014; Sheroziya and Timofeev, 2014; McCormick et al., 2015), as opposed to merely serving a relay function and is consistent with a diverse…”

“S1 and S2 receive common input from M1 and POm, conveying efferent and re-afferent motor information (Deschenes et al., 1998; Suter and Shepherd, 2015), and are additionally coupled by thalamic relays through POm (Theyel et al., 2010) (Figure 7).”

“However, the vast majority of thalamic sub-regions are formed by higher order relay nuclei, which not only have reciprocal projections with distinct cortical regions but also have non-reciprocal projections from many cortical areas that are not innervated by those nuclei or belong to another circuit system (Guillery a…”

“We have documented such a circuit from S1 to S2 (Theyel et al., 2010), but the possibility exists that areas other than S2 and M1 receive trans-thalamic input via POm from S1.”

“This higher-order thalamus forms pathways between cortical areas, which can strongly influence cortical activity (Theyel et al., 2010; Purushothaman et al., 2012; Saalmann et al., 2012).”

“…5 project back to cortex, this top-down drive can form the basis of a corticocortical information transfer via the thalamus, as shown previously (Theyel et al., 2010), and can mediate higher-order sensory procession, which requires coordinated control of topdown and bottom-up signal flows…”

“…or even replacement of, the current dogma that corticocortical transfer of primary information exclusively involves direct corticocortical pathways" (Theyel et al., 2010) In just this vein, Sherman and Guillery (2013) argue that large amounts of thalamic connectivity are not simple way-stations or…”

“POm is known to be a potent driver of activity in secondary somatosensory (S2) in vitro (Theyel et al., 2010), and a recent in vivo study of anesthetized mice found that POm input could enhance the responsiveness of L5 pyramidal neurons to sensory stimulation (Mease et al.”

“One possibility is that the cortico-pulvino-cortical pathway operates in parallel with the direct corticocortical pathways, but is specialized in providing target cortical areas with an efference copy of the signals relayed to subcortical structures by the source layer 5 neurons [67,69].”

“…, leading to different absolute numbers of neurons activated during a task (for example, see small amount of thalamic activation needed to drive large cortical activations in (Llano et al., 2009; Theyel, Llano, & Sherman, 2010)), leading to different metabolic signatures in each structure.”

“It is well known that both SI and SII project back to the ipsilateral thalamus through reciprocal connections (Iyengar et al., 2007; Krubitzer and Kaas, 1992; Qi et al., 2002), and that thalamic activity may be modulated by these corticothalamic inputs (Theyel et al., 2010).”

“While this hypothesis has not been fully tested with in vivo experiments, the existence of cortical-thalamo-cortical signal transmission has been demonstrated in vitro (Theyel et al., 2010).”

“Synapses from the cortex onto thalamocortical neurons outnumber ascending projections to the thalamus by at least 3:1 (Erisir et al., 1997; Van Horn et al., 2000), and can strongly modulate thalamic output (Groh et al., 2008; Reichova & Sherman, 2004; Theyel et al., 2010).”

“(2006) and subsequently confirmed (Petreanu et al., 2009; Theyel et al., 2010; Mao et al., 2011; Viaene et al., 2011; Gambino et al., 2014; Jouhanneau et al., 2014).”

“On the other hand, projections from multisensory thalamic nuclei as well as feedback projections from higher-order convergence areas (Theyel et al., 2010) might account for the delayed lidocaineinsensitive peaks of phase concentration.”

“…in different cortical subnetworks, have different intrinsic properties, different patterns of projections to the thalamus, and possibly, different roles in shaping thalamic function (Ojima, 1994; Reichova and Sherman, 2004; Llano and Sherman, 2008; Llano and Sherman, 2009; Theyel et al., 2010).”

“Both areas receive corticocortical projections from S1 (see Introduction) and thalamocortical projections from the posterior (PO) nucleus of the thalamus (Herkenham, 1980; Burton, 1986; Theyel et al., 2010; Pouchelon et al., 2014).”

“…established by cortical driver inputs to the thalamus have also been studied in slice preparations from mice, clearly demonstrating that these corticothalamic axons are drivers, sending inputs to the thalamus for relay to higher cortical areas (Reichova and Sherman 2004; Theyel et al., 2010).”

“In the somatosensory cortex, subpopulations of L5 PCs project to thalamic nuclei, which subsequently send excitatory afferents to higher-order cortical sensory areas (Theyel et al. 2010; Sherman and Guillery 2011).”

“Specific areas of the thalamus receive afferent input and send efferent projections to distinct areas of the cortex, forming the purported cortico-thalamo-cortical pathways (Theyel et al., 2010; Purushothaman et al., 2012; Saalmann et al., 2012).”

“In addition, there could be another contribution to the structured spontaneous activity from the corticothalamocortical circuit, which could have a role in signal propagation from primary to higher auditory areas even in absence of corticocortical connections (Theyel et al., 2009).”

“The neurons in S2 receive three different synaptic inputs: directly from VPL (47), directly from S1, and indirectly from S1 via PO (18, 46).”

“, 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., 2010).”

“…control (Sommer and Wurtz 2006; Sommer 2003; Goldberg and Fee 2012), mediates communication between cortical areas, modulates cortico-cortical synchrony (Theyel et al. 2010; Purushothaman et al. 2012; Saalmann et al. 2012) and controls cortical states (Crunelli and Hughes 2010; Poulet et al. 2012).”

“In this way, the thalamus plays a key role in corticocortical information flow and in modulating the activity of cortical networks (Theyel et al. 2010; Saalmann and Kastner 2011).”

“This CxTh activity in turn projects back to other parts of the cortex, representing therefore a thalamic pathway for CxCx interaction [57].”

“Layer 6 inputs to thalamus subserve a modulatory function and thus are not thought to provide information to be relayed back to cortex, whereas layer 5 inputs have driver properties and are thought to provide information for thalamocortical relay, which suggests that these transthalamic routes represent information st…”

“…subcortical targets (Fries et al., 1985; Hübener and Bolz, 1988; Kasper et al., 1994; Zhang and Deschênes, 1997; Hallman et al., 1998; Mercer et al., 2005; Molnár and Cheung, 2006; West et al., 2006; Hattox and Nelson, 2007; Brown and Hestrin, 2009; also see Thomson, 2010, for a review).”