Barrel cortex function

“Two-photon calcium imaging in L2/3 of barrel cortex in vivo (Helmchen and Denk, 2005; Wallace et al., 2008; Grewe and Helmchen, 2009) has provided additional insights into the spatiotemporal aspects of population reponses.”

“This subcellular target structure specificity of the inhibitory neurons’ axon is the hallmark of many classifications and has been suggested to be independent of the laminar location of the cell body within a cortical column (Markram et al., 2004), but this view is far from unequivocal.”

“Particular potential is offered further by in vivo calcium imaging using genetically-encoded calcium indicators (GECIs) such as GCaMP-3 (Tian et al., 2009) or Yellow Cameleon 3.60 (Nagai et al., 2004; Lütcke et al., 2010).”

“From data obtained in cat visual cortex, Douglas and Martin defined a ‘canonical’ microcircuit of neocortex implying that most cortical areas have a rather similar basic neuronal network structure (Gilbert and Wiesel, 1983; Gilbert, 1983; Douglas and Martin, 1991, 2004).”

“…different molecules and their combinations, including oligopeptide co-transmitters, calcium binding proteins, and receptor subunits, suggesting a huge functional variability amongst cortical GABAergic neurons (Markram et al., 2004; Sugino et al., 2006; Ascoli et al., 2008; Taniguchi et al., 2011).”

“Knowledge about its development may contribute important aspects needed to understand its mechanisms of operation in the adult, both under physiological as well as pathophysiological conditions, such as neurodevelopmental disorders (for review Amaral et al., 2008; Courchesne et al., 2007).”

“The literature on neocortical GABAergic neurons is vast and many efforts have been made to describe their features and to characterize their synaptic connections (e.g. Ascoli et al., 2008).”

“Together with the PV and SST neurons, 5HT3aR cells have been reported to capture virtually 100% of cortical GABAergic neurons (Lee et al., 2010; Rudy et al., 2011).”

“(Kawaguchi and Kubota, 1997) proposed to divide them into three groups: parvalbumin expressing (PV, a calcium binding protein), somatostatin expressing (SST), and vasoactive intestinal polypeptide expressing (VIP) (both SST and VIP are oligopeptide co-”

“Likewise monoaminergic innervations play important roles in barrel formation (for review see Gaspar et al., 2003).”

“acetylcholine (ACh), norepinephrine (NE), and other neurotransmitters which act in thalamus and cortex amongst other structures (McCormick and Bal, 1997; Buzsaki et al., 1988; Kristt, 1979; Kristt and Waldman, 1981; Houser et al., 1985).”

“…of perceptual tasks that reflect specific characteristics of the conditioned stimulus (CS) in space and time (Disterhoft and Stuart, 1976; Kitzes et al., 1978; Diamond and Weinberger, 1986; Diamond and Weinberger, 1989; Recanzone et al., 1992, 1993; Schoups et al., 2001; Ghose et al., 2002).”

“scheme of ‘canonical’ microcircuitry have to be interpreted cautiously in the absence of a full connectionist cortical model (Markram, 2006; Helmstaedter et al., 2007), as columnar dynamics have been shown to deviate from the sequence expected from the microcircuit known so far.”

“Excitatory GABAergic synapses contribute initially to synchronized network activity (Owens and Kriegstein, 2002; Daw et al., 2007),”

“and L2/3 (White, 1978; Petreanu et al., 2009; Meyer et al., 2010; Oberlaender et al., 2012).”

“A major role is played by acetylcholine (ACh), norepinephrine (NE), and other neurotransmitters which act in thalamus and cortex amongst other structures (McCormick and Bal, 1997; Buzsaki et al., 1988; Kristt, 1979; Kristt and Waldman, 1981; Houser et al., 1985).”

“60 (Nagai et al., 2004; Lütcke et al., 2010).”

“From data obtained in cat visual cortex, Douglas and Martin defined a ‘canonical’ microcircuit of neocortex implying that most cortical areas have a rather similar basic neuronal network structure (Gilbert and Wiesel, 1983; Gilbert, 1983; Douglas and Martin, 1991, 2004).”

“More frontally, cortex assumes anatomical and functional properties reminiscent to pre-motor and pre-frontal areas in primates (Uylings et al., 2003).”

“4A) (Markram et al., 1997; Reyes et al., 1998; Feldmeyer et al., 1999, 2002, 2006; Petersen and Sakmann, 2000; Lübke et al., 2000, 2003; Schubert et al., 2001, 2003; Silver et al., 2003; Bureau et al., 2006; Lefort et al., 2009; Petreanu et al., 2009).”

“First experiments combining genetic manipulation with cellular imaging employed in animals trained to perform sophisticated behavior have been conducted (Harvey et al., 2012) and optogenetic stimulation has been used for a detection task (Huber et al., 2008).”

“…exist with bilateral perirhinal cortex (Chakrabarti and Alloway, 2006; Ferezou et al., 2007; Sato and Svoboda, 2010; Aronoff et al., 2010), the contralateral somatosensory cortex (Petreanu et al., 2007), and contralateral motor cortex and ipsilateral orbitofrontal cortex (Aronoff et al., 2010).”

“, 2008) and possibly also to the parahippocampal region and hippocampus (Witter et al., 1986).”

“M1 is located fronto-medially from S1, shares input from POm and overlaps the limb S1 representation (Hall and Lindholm, 1974).”

“In the barrel column L4 spiny neurons target L5A pyramidal neurons (amongst projections to all other cortical layers; Feldmeyer et al., 2005; Schubert et al., 2006; Lefort et al., 2009), a projection that has not been identified for V1 (Fig.”

“Two further groups developed early on a paradigm that is based on instrumental learning to test the whisker-related percept (Guic-Robles et al., 1989; Carvell and Simons, 1990; Guic-Robles et al., 1992).”

“…(i) monitoring of large populations of neurons, (ii) determining the function of genetically labeled, or post hoc histologically identified neurons (Bock et al., 2011; Langer and Helmchen F, 2012), and (iii) is starting to be combined with detailed behavioral observation in trained animals…”

“Knowledge about its development may contribute important aspects needed to understand its mechanisms of operation in the adult, both under physiological as well as pathophysiological conditions, such as neurodevelopmental disorders (for review Amaral et al., 2008; Courchesne et al., 2007).”

“Sensory cortices seem to contribute to perception because they undergo plastic changes during learning of perceptual tasks that reflect specific characteristics of the conditioned stimulus (CS) in space and time (Disterhoft and Stuart, 1976; Kitzes et al., 1978; Diamond and Weinberger, 1986; Diamond and Weinberger, 19…”

“higher-order branching of basal dendrites in L2/3 neurons and dendritic spine motility (Lendvai et al., 2000; Maravall et al., 2004a), or pruning of thalamocortical axons in their final termination area in L4 of a single barrel (Bender”

“For sensory systems this question is asked by studies on the physiology of perception (Parker and Newsome, 1998), involving simultaneous measurement of neuronal activity and the subject’s behavior and percept.”

“Extracellular measures of global sub-threshold synaptic activity in barrel cortex of awake mice using local field potential recordings (Poulet and Petersen, 2008) or voltage sensitive dye imaging (Ferezou et al.”

“visual signals in V2 – while projections within V1 are isotropic (Angelucci et al., 2002).”

“Accordingly, frequency adaptation (i.e. response reduction with repetitive whisker stimulation) is commonly observed in the cortex (Simons, 1978, 1985; Garabedian et al., 2003; Arabzadeh et al., 2003; Hartings et al., 2003; Webber and Stanley, 2004; Khatri et al., 2004; Stüttgen and Schwarz, 2010;…”

“…of perceptual tasks that reflect specific characteristics of the conditioned stimulus (CS) in space and time (Disterhoft and Stuart, 1976; Kitzes et al., 1978; Diamond and Weinberger, 1986; Diamond and Weinberger, 1989; Recanzone et al., 1992, 1993; Schoups et al., 2001; Ghose et al., 2002).”

“The first is the disynaptic inhibition of pyramidal cells by intervening Martinotti cells (Silberberg and Markram, 2007; Berger et al., 2009; Murayama et al., 2009), the second is the preferential innervation of L6 inhibitory neurons by corticothalamic pyramidal cells (West et al., 2006; see also…”

“From data obtained in cat visual cortex, Douglas and Martin defined a ‘canonical’ microcircuit of neocortex implying that most cortical areas have a rather similar basic neuronal network structure (Gilbert and Wiesel, 1983; Gilbert, 1983; Douglas and Martin, 1991, 2004).”

“In addition, modern methods of precise and specific stimulation like caged glutamate release and optogenetic approaches have been used (for reviews see Helmstaedter et al., 2007; Petersen, 2007; Schubert et al., 2007; Lübke and Feldmeyer, 2007).”

“Thus, somatosensory and motor signals are expected to interact constantly, a fact that is reflected by a dense interconnection of the two systems on all levels of organization (Ferezou et al., 2007; Diamond et al., 2008; Sato and Svoboda, 2010; Petreanu et al., 2012) (Fig.”

“…by paired recordings – appears to be present: Bipolar-bitufted VIP cells, numerous in L2/3, sample signals from local pyramidal neurons (Porter et al., 1998; Reyes et al., 1998; Rozov et al., 2001) and target L5 pyramidal cells with their rich columnar axons (Bayraktar et al., 2000) (Fig.”

“Together these strong inhibitory effects in L4 are thought to set a short window for synaptic integration by excitatory L4 cells (Brecht and Sakmann, 2002a; Pinto et al., 2003; Bruno and Sakmann, 2006; Wang et al., 2010).”

“For instance, ectopic expression of the fibroblast growth factor 8 leads to a partial duplication of the barrel field (Fukuchi-Shimogori and Grove, 2001).”

“…during whisking movements in air or against objects (Fanselow and Nicolelis, 1999; Hentschke et al., 2006; Lee et al., 2006; Crochet and Petersen, 2006; Fujisawa et al., 2008; Poulet and Petersen, 2008; Jadhav et al., 2009a; Ferezou et al., 2007; Greenberg et al., 2008; Sawinski et al., 2009).”

“Single-whisker deflection leads to an initially confined activation of the respective barrel column followed by a rapid horizontal spread across the entire barrel field within 50 ms (Petersen et al., 2003a) (Fig.”

“4A) (Markram et al., 1997; Reyes et al., 1998; Feldmeyer et al., 1999, 2002, 2006; Petersen and Sakmann, 2000; Lübke et al., 2000, 2003; Schubert et al., 2001, 2003; Silver et al., 2003; Bureau et al., 2006; Lefort et al., 2009; Petreanu et al., 2009).”

“behavior (Guillery and Sherman, 2002).”

“At birth, the subplate mediates spindle bursts and gamma oscillations to the cortical plate (Khazipov et al., 2004; Minlebaev et al., 2007; Yang et al., 2009; Minlebaev et al., 2011).”

“straddles what has been called the agranular medial and lateral fields (AGL and AGM, Brecht et al., 2004; Neafsey et al., 1986).”

“Together with the PV and SST neurons, 5HT3aR cells have been reported to capture virtually 100% of cortical GABAergic neurons (Lee et al., 2010; Rudy et al., 2011).”

“Galvez et al. (2007) conducted experiments that directly showed that barrel cortex contribution to acquisition and retention of the classically conditioned eye lid reflex is indeed critical if the CS and US are presented in sequence, separate in time, while in the case CS and US overlapped in time, learning occurred e…”

“function of these inputs in intracortical processing (Beierlein et al., 2003; Tan et al., 2008).”

“Modified with permission from (Lübke and Feldmeyer, 2007). D. Feldmeyer et al. / Progress in Neurobiology 103 (2013) 3–27 9”

“Excitatory GABAergic synapses contribute initially to synchronized network activity (Owens and Kriegstein, 2002; Daw et al., 2007), but at the beginning of the second postnatal week shift to inhibitory action (Luhmann and Prince, 1991; for review see Kilb, 2011).”

“In a second step, repeated processing within the same context leads to the learning of the respective behavior – possibly laid down as memory traces in cortical circuits (Fuster, 2009).”

“In addition to this disynaptic feed-forward mechanism, trisynaptic feedback inhibition via reciprocal synapse between spiny stellate and inhibitory neurons with a high connectivity ratio exists as well (Kölbl et al., 2010; Cruikshank et al., 2007; Daw et al., 2007).”

“When mice start to move their whiskers, with no objects in the way, the slow oscillations are reduced in amplitude and replaced by faster, lower amplitude synaptic activity (Crochet and Petersen, 2006; Poulet and Petersen, 2008) (Fig.”

“Together, ACh-related effects may increase signal to noise ratio for behaviorally relevant signals (Gil et al., 1997; Oldford and CastroAlamancos, 2003; Gulledge and Stuart, 2005; Eggermann and Feldmeyer, 2009; Gulledge and Kawaguchi, 2007; Porter et al., 1999; Christophe et al., 2002).”

“(2010). feedback system is a gatekeeper of its own input but has limited potential to couple far distant neocortical sites (Olsen et al., 2012, but see Zhang and Deschênes, 1997).”

“The same set of signals were found to be encoded in M1 L2/3 neurons the major site of origin for M1-S1 projection (Mao et al., 2011; Huber et al., 2012), suggesting that M1-S1 communication via direct cortico–cortical fibers is comprehensive and thus may play an important role in sensorimotor…”

“As expected it is shaped by intracortical inhibition (Moore and Nelson, 1998; Butovas et al., 2006), but there is also considerable evidence that short term dynamics of thalamocortical (and possibly also intracortical) synapses play a role (CastroAlamancos and Oldford, 2002; Chung et al., 2002).”

“It is important to point out that these properties already exist on the ascending pathway but are transformed at the entry to the barrel cortex (Simons and Carvell, 1989).”

“Barrels receive their ascending input predominantly from one whisker, the so-called principal whisker (Welker, 1976; Simons, 1978).”

“…these subplate-driven events are dependent on electrical synapses and synchronize local neuronal networks of 200–400 mm in horizontal dimension, thus constituting cortical ‘pre-columns’ or ‘neuronal domains’ (Yang et al., 2009; Yuste et al., 1992; Dupont et al., 2006; Sun and Luhmann, 2007).”

“The subsequent formation of early cortical circuits, however, is in many aspects regulated by spontaneous and periphery-driven neuronal activity and by the influence of neuromodulatory systems (Khazipov and Luhmann, 2006; Allene and Cossart, 2010).”

“It has been shown that texture discrimination (Carvell and Simons, 1990) as well as object localization (Knutsen et al., 2006; O’Connor et al., 2010a,b) can be performed with a single whisker suggesting that multi-whisker integration is not a strong requirement, at least for the so far tested…”

“Furthermore, the horizontal spread of the sensory response has been observed to be decreased (Hentschke et al., 2006; Ferezou et al., 2006) (Fig.”

“Furthermore, neuronal activity evoked by electrical microstimulation (Butovas and Schwarz, 2007), optogenetic stimulation (Huber et al., 2008) and even juxtacellular stimulation of single neurons (Houweling and Brecht, 2008) in V1 and barrel cortex are perceived by rodents.”

“From data obtained in cat visual cortex, Douglas and Martin defined a ‘canonical’ microcircuit of neocortex implying that most cortical areas have a rather similar basic neuronal network structure (Gilbert and Wiesel, 1983; Gilbert, 1983; Douglas and Martin, 1991, 2004).”

“4A) (Markram et al., 1997; Reyes et al., 1998; Feldmeyer et al., 1999, 2002, 2006; Petersen and Sakmann, 2000; Lübke et al., 2000, 2003; Schubert et al., 2001, 2003; Silver et al., 2003; Bureau et al., 2006; Lefort et al., 2009; Petreanu et al., 2009).”

“At P0, this cholinergic input is confined to the cortical subplate (Hanganu and Luhmann, 2004; Dupont et al., 2006; Hanganu et al., 2009), where it causes a pronounced excitation and burst firing of subplate cells (for reviews see Luhmann et al., 2009; Kanold and Luhmann, 2010) (Fig.”

“…have also been identified in the rodent barrel cortex (Bayraktar et al., 2000; Porter et al., 2001; Angulo et al., 2003; Staiger et al., 2004; Ma et al., 2006; Sun et al., 2006; David et al., 2007; Tan et al., 2008; Karagiannis et al., 2009; Sun, 2009; Staiger et al., 2009; Helmstaedter et…”

“L2/3, as tactile information of L4 microcircuits is not only transferred to supragranular pyramidal neurons, but also with high efficacy to several types of L2/3 inhibitory neurons (Helmstaedter et al., 2008; Xu and Callaway, 2009; Xu et al., 2010) (Fig.”

“In vivo two-photon microscopy has recently been used to target whole-cell recordings to L2/3 inhibitory and excitatory neurons during resting and active states in mouse barrel cortex (Gentet et al., 2010) (Fig.”

“Interestingly, the projection from S1 to SpVi also appears to be directly involved in controlling whisker movements, since stimulation of S1 neurons when M1 is inactivated, and SpVi stimulation alone drives retraction of the contralateral whisker (Matyas et al., 2010).”

“A reverse tendency exists for the projection from L6 to L4, which is functionally well characterized in V1 (Bolz et al., 1989; Stratford et al., 1996; TarczyHornoch et al., 1999) but has not been characterized in the barrel column (Lefort et al., 2009; but see Zhang and Deschênes, 1997; Kumar and…”

“Single-whisker deflection leads to an initially confined activation of the respective barrel column followed by a rapid horizontal spread across the entire barrel field within 50 ms (Petersen et al., 2003a) (Fig.”

“Activation of barrel cortex follows a laminar pattern (Armstrong-James et al., 1992; Welker et al., 1993; Celikel et al., 2004).”

“At that age layer (L) 4 plasticity has diminished and predominantly occurs in L2/3 and L5 (Diamond et al., 1994; Fox, 1992).”

“…during whisking movements in air or against objects (Fanselow and Nicolelis, 1999; Hentschke et al., 2006; Lee et al., 2006; Crochet and Petersen, 2006; Fujisawa et al., 2008; Poulet and Petersen, 2008; Jadhav et al., 2009a; Ferezou et al., 2007; Greenberg et al., 2008; Sawinski et al., 2009).”

“barrel cortex L5 neurons sending collaterals to POm (Hoogland et al., 1991; Bourassa et al., 1995; Veinante et al., 2000b; Killackey and Sherman, 2003), a higher thalamic nucleus which connects to several sensorimotor cortical areas (S1, S2, PM, M1, amongst”

“These results in rats comparing slow wave anesthetized and desynchronized awake cortical states (Constantinople and Bruno, 2011) need to be reconciled with findings in mice comparing the slow wave cortical state during quiet wakefulness and the desynchronised active whisking state (Poulet et al.,…”

“acetylcholine (ACh), norepinephrine (NE), and other neurotransmitters which act in thalamus and cortex amongst other structures (McCormick and Bal, 1997; Buzsaki et al., 1988; Kristt, 1979; Kristt and Waldman, 1981; Houser et al., 1985).”

“…to those known from other cortical systems, particularly V1 in cats and monkeys, where the cortico-cortical output of a column projects in a clustered fashion - each cluster being a dense innervation of a circumscribed column (Koralek et al., 1990; Lund et al., 1993; Douglas and Martin, 2004).”

“…circuitry by the subplate, a layer of early-born GABAergic and glutamatergic neurons, which show mature functional properties (for reviews see Sur and Leamey, 2001; López-Bendito and Molnár, 2003; Kanold and Luhmann, 2010) and are receptive to acetylcholinergic neuromodulation (Dupont et…”

“…sending collaterals to POm (Hoogland et al., 1991; Bourassa et al., 1995; Veinante et al., 2000b; Killackey and Sherman, 2003), a higher thalamic nucleus which connects to several sensorimotor cortical areas (S1, S2, PM, M1, amongst others) (Deschênes et al., 1998; Chmielowska et al., 1989) (Fig.”

“The first is the disynaptic inhibition of pyramidal cells by intervening Martinotti cells (Silberberg and Markram, 2007; Berger et al., 2009; Murayama et al., 2009), the second is the preferential innervation of L6 inhibitory neurons by corticothalamic pyramidal cells (West et al., 2006; see also…”

“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).”

“Elucidating the function of cortical networks requires an interplay between anatomical and physiological analyses, as has been emphasized repeatedly by earlier reviews of cortical function (e.g. Douglas and Martin, 2007; O’Connor et al., 2009).”

“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).”

“Thus, somatosensory and motor signals are expected to interact constantly, a fact that is reflected by a dense interconnection of the two systems on all levels of organization (Ferezou et al., 2007; Diamond et al., 2008; Sato and Svoboda, 2010; Petreanu et al., 2012) (Fig.”

“…make highresolution electrophysiological and optical recordings from neocortex in awake rodents during whisking movements in air or against objects (Fanselow and Nicolelis, 1999; Hentschke et al., 2006; Lee et al., 2006; Crochet and Petersen, 2006; Fujisawa et al., 2008; Poulet and Petersen, 2008;…”

“However, relating response patterns to the neuron type by juxtacellular recordings and subsequent neuronal reconstruction (de Kock et al., 2007; de Kock and Sakmann, 2008) confirmed layerspecific delays of transient responses but showed clear deviation from what would be expected from the known…”

“…and reconstructed using thalamocortical synapses from VPM, which target not only L4 spiny neurons, but also various types of fast spiking inhibitory neurons (Porter et al., 2001; Gabernet et al., 2005; Sun et al., 2006; Cruikshank et al., 2007; Kimura et al., 2010; Staiger et al., 1996) (Fig.”

“A current consensus is that trans-columnar processing plays generally a leading role in shaping excitatory and inhibitory parts of receptive fields (Moore and Nelson, 1998; Brecht and Sakmann, 2002a).”

“The conclusion from this has been that neocortical circuits either lose information, or at least represent it using highly intricate (e.g. nonlinear) ways (Wu et al., 2006).”

“…of this notion, there is ample evidence indicating that the brain structures critical for classical delay conditioning (cerebellum, brainstem: Clark et al., 1984; Mauk and Thompson, 1987) are different from those necessary for trace conditioning (hippocampus, neocortex, cerebellum: Weiss et…”

“areas as well and have been proposed as a general means to couple different neocortical areas (Sherman and Guillery, 2011).”

“Accordingly, frequency adaptation (i.e. response reduction with repetitive whisker stimulation) is commonly observed in the cortex (Simons, 1978, 1985; Garabedian et al., 2003; Arabzadeh et al., 2003; Hartings et al., 2003; Webber and Stanley, 2004; Khatri et al., 2004; Stüttgen and Schwarz, 2010;…”

“events are dependent on electrical synapses and synchronize local neuronal networks of 200–400 mm in horizontal dimension, thus constituting cortical ‘pre-columns’ or ‘neuronal domains’ (Yang et al., 2009; Yuste et al., 1992; Dupont et al., 2006; Sun and Luhmann, 2007).”

“…exist with bilateral perirhinal cortex (Chakrabarti and Alloway, 2006; Ferezou et al., 2007; Sato and Svoboda, 2010; Aronoff et al., 2010), the contralateral somatosensory cortex (Petreanu et al., 2007), and contralateral motor cortex and ipsilateral orbitofrontal cortex (Aronoff et al., 2010).”

“A current consensus is that trans-columnar processing plays generally a leading role in shaping excitatory and inhibitory parts of receptive fields (Moore and Nelson, 1998; Brecht and Sakmann, 2002a).”

“These results in rats comparing slow wave anesthetized and desynchronized awake cortical states (Constantinople and Bruno, 2011) need to be reconciled with findings in mice comparing the slow wave cortical state during quiet wakefulness and the desynchronised active whisking state (Poulet et al., 2012).”

“4A) (Markram et al., 1997; Reyes et al., 1998; Feldmeyer et al., 1999, 2002, 2006; Petersen and Sakmann, 2000; Lübke et al., 2000, 2003; Schubert et al., 2001, 2003; Silver et al., 2003; Bureau et al., 2006; Lefort et al., 2009; Petreanu et al., 2009).”

“During this early postnatal period, layer 4 in rat barrel cortex shows prominent activity-dependent plasticity to whisker plucking with an expansion of the cortical representation responding to the spared whisker (for review Fox, 2002) (Fig.”

“Sensory cortices seem to contribute to perception because they undergo plastic changes during learning of perceptual tasks that reflect specific characteristics of the conditioned stimulus (CS) in space and time (Disterhoft and Stuart, 1976; Kitzes et al., 1978; Diamond and Weinberger, 1986; Diamond and Weinberger, 19…”

“The sensory signal flow towards the barrel column starts in the primary afferent fibers that innervate the whisker follicle using a variety of specialized end organs, including Merkel cells, lanceolateand club-shaped endings, and free nerve endings (Ebara et al., 2002).”

“…and intracellular measurements revealed that receptive fields of thalamic and cortical neurons of all layers in barrel and septal columns are surprisingly broad (Simons, 1978; Moore and Nelson, 1998; Zhu and Connors, 1999; Brecht and Sakmann, 2002a,b; Brecht et al., 2003; Manns et al., 2004).”

“4A) (Markram et al., 1997; Reyes et al., 1998; Feldmeyer et al., 1999, 2002, 2006; Petersen and Sakmann, 2000; Lübke et al., 2000, 2003; Schubert et al., 2001, 2003; Silver et al., 2003; Bureau et al., 2006; Lefort et al., 2009; Petreanu et al., 2009).”

“and L2/3 (White, 1978; Petreanu et al., 2009; Meyer et al., 2010; Oberlaender et al., 2012).”

“network firing is greatly reduced and decorrelated, and thus approaches the characteristic firing patterns of the adult network (Maravall et al., 2004a,b; Golshani et al., 2009).”

“revealed that the major excitatory pathways of the canonical microcircuitry defined by Douglas and Martin are present, as recently reviewed in detail (Feldmeyer, 2012; Ahissar and Staiger, 2010).”

“subfields are generated by intracortical mechanisms (Carvell and Simons, 1988; Moore and Nelson, 1998; Schubert et al., 2001, 2003; Brecht et al., 2003; Manns et al., 2004).”

“Furthermore, as in V1, a thalamo–cortico–thalamic feedback loop exists in which the two major thalamorecipient layers (L4 and L6A) are interconnected and report the cortical state of activity back to the thalamus (Zhang and Deschênes, 1997; Thomson, 2010; Briggs, 2010) (Fig.”

“At that age layer (L) 4 plasticity has diminished and predominantly occurs in L2/3 and L5 (Diamond et al., 1994; Fox, 1992).”

“It has been shown that texture discrimination (Carvell and Simons, 1990) as well as object localization (Knutsen et al., 2006; O’Connor et al., 2010a,b) can be performed with a single whisker suggesting that multi-whisker integration is not a strong requirement, at least for the so far tested…”

“Furthermore, as in V1, a thalamo–cortico–thalamic feedback loop exists in which the two major thalamorecipient layers (L4 and L6A) are interconnected and report the cortical state of activity back to the thalamus (Zhang and Deschênes, 1997; Thomson, 2010; Briggs, 2010) (Fig.”

“At birth, the subplate mediates spindle bursts and gamma oscillations to the cortical plate (Khazipov et al., 2004; Minlebaev et al., 2007; Yang et al., 2009; Minlebaev et al., 2011).”

“…form unusually strong projections to supragranular layers with enhanced input to L2 excitatory neurons which, in septal columns, seem to even dominate the L2/3 inputs (Shepherd and Svoboda, 2005; Bureau et al., 2006; Lefort et al., 2009; Oberlaender et al., 2011a), a feature not known from V1.”

“…sending collaterals to POm (Hoogland et al., 1991; Bourassa et al., 1995; Veinante et al., 2000b; Killackey and Sherman, 2003), a higher thalamic nucleus which connects to several sensorimotor cortical areas (S1, S2, PM, M1, amongst others) (Deschênes et al., 1998; Chmielowska et al., 1989) (Fig.”

“For instance it has been shown that conditioning of detection and discrimination performance of tactile frequency is possible after a near-complete lesion of the barrel cortex (Hutson and Masterton, 1986).”

“Single whisker stimulation caused the largest number of spikes in the neuronal population of the principal barrel column, but in addition elicited clear calcium transients in the adjacent columns (Sato et al., 2007; Kerr et al., 2007) (Fig.”

“Finally the ‘paralemniscal’ projection starts from multi-whisker cells in the caudal part of SpVi (SpVic) and projects via the anterior POm to barrel cortex L1 and L5a irrespective of barrel and septal columns (Veinante et al., 2000b Wimmer et al., 2010; Ohno et al., 2011).”

“Together, ACh-related effects may increase signal to noise ratio for behaviorally relevant signals (Gil et al., 1997; Oldford and CastroAlamancos, 2003; Gulledge and Stuart, 2005; Eggermann and Feldmeyer, 2009; Gulledge and Kawaguchi, 2007; Porter et al., 1999; Christophe et al., 2002).”

“M1 is located fronto-medially from S1, shares input from POm and overlaps the limb S1 representation (Hall and Lindholm, 1974).”

“Two further groups developed early on a paradigm that is based on instrumental learning to test the whisker-related percept (Guic-Robles et al., 1989; Carvell and Simons, 1990; Guic-Robles et al., 1992).”

“At birth, the subplate mediates spindle bursts and gamma oscillations to the cortical plate (Khazipov et al., 2004; Minlebaev et al., 2007; Yang et al., 2009; Minlebaev et al., 2011).”

“…been identified in the rodent barrel cortex (Bayraktar et al., 2000; Porter et al., 2001; Angulo et al., 2003; Staiger et al., 2004; Ma et al., 2006; Sun et al., 2006; David et al., 2007; Tan et al., 2008; Karagiannis et al., 2009; Sun, 2009; Staiger et al., 2009; Helmstaedter et al., 2009a,b,c).”

“…from neocortex in awake rodents during whisking movements in air or against objects (Fanselow and Nicolelis, 1999; Hentschke et al., 2006; Lee et al., 2006; Crochet and Petersen, 2006; Fujisawa et al., 2008; Poulet and Petersen, 2008; Jadhav et al., 2009a; Ferezou et al., 2007; Greenberg…”

“4A) (Markram et al., 1997; Reyes et al., 1998; Feldmeyer et al., 1999, 2002, 2006; Petersen and Sakmann, 2000; Lübke et al., 2000, 2003; Schubert et al., 2001, 2003; Silver et al., 2003; Bureau et al., 2006; Lefort et al., 2009; Petreanu et al., 2009).”

“textures and found that so-called stick-and-slip events are generated depending on the roughness of textures, and thus, could contribute significantly to perception (Wolfe et al., 2008; Jadhav et al., 2009a).”

“The sub-cortical pathway departs mostly from L5 large pyramids that – beyond thalamus – project as well to brainstem, reticular formation, tectum, the basal ganglia, and the cerebellar networks amongst others (see for review, Bosman et al. (2011); see also Kozloski et al.”

“…form unusually strong projections to supragranular layers with enhanced input to L2 excitatory neurons which, in septal columns, seem to even dominate the L2/3 inputs (Shepherd and Svoboda, 2005; Bureau et al., 2006; Lefort et al., 2009; Oberlaender et al., 2011a), a feature not known from V1.”

“…been identified in the rodent barrel cortex (Bayraktar et al., 2000; Porter et al., 2001; Angulo et al., 2003; Staiger et al., 2004; Ma et al., 2006; Sun et al., 2006; David et al., 2007; Tan et al., 2008; Karagiannis et al., 2009; Sun, 2009; Staiger et al., 2009; Helmstaedter et al., 2009a,b,c).”

“, 2010) and rats (Okun et al., 2010) (Fig.”

“…notion, there is ample evidence indicating that the brain structures critical for classical delay conditioning (cerebellum, brainstem: Clark et al., 1984; Mauk and Thompson, 1987) are different from those necessary for trace conditioning (hippocampus, neocortex, cerebellum: Weiss et al., 2006).”

“In summary, while the situation in L4 remains not fully resolved, there is otherwise consensus that inhibitory and excitatory subfields are generated by intracortical mechanisms (Carvell and Simons, 1988; Moore and Nelson, 1998; Schubert et al., 2001, 2003; Brecht et al., 2003; Manns et al., 2004).”

“Frequency adaptation has been proposed to be modulated by the level of alertness as it has been observed to be reduced during learning, but reappeared prominently after a task has been mastered (Castro-Alamancos, 2004).”

“…during whisking movements in air or against objects (Fanselow and Nicolelis, 1999; Hentschke et al., 2006; Lee et al., 2006; Crochet and Petersen, 2006; Fujisawa et al., 2008; Poulet and Petersen, 2008; Jadhav et al., 2009a; Ferezou et al., 2007; Greenberg et al., 2008; Sawinski et al., 2009).”

“However, individual neighboring neurons could also show highly heterogeneous responses (Sato et al., 2007).”

“…and reconstructed using thalamocortical synapses from VPM, which target not only L4 spiny neurons, but also various types of fast spiking inhibitory neurons (Porter et al., 2001; Gabernet et al., 2005; Sun et al., 2006; Cruikshank et al., 2007; Kimura et al., 2010; Staiger et al., 1996) (Fig.”

“infer the vibrations of the whisker at the shaft, the location that directly stimulates the follicle because biomechanical transformation of tip deflection to shaft vibration is potentially complex (Neimark et al., 2003; Hartmann et al., 2003).”

“In the barrel column L4 spiny neurons target L5A pyramidal neurons (amongst projections to all other cortical layers; Feldmeyer et al., 2005; Schubert et al., 2006; Lefort et al., 2009), a projection that has not been identified for V1 (Fig.”

“L2/3, as tactile information of L4 microcircuits is not only transferred to supragranular pyramidal neurons, but also with high efficacy to several types of L2/3 inhibitory neurons (Helmstaedter et al., 2008; Xu and Callaway, 2009; Xu et al., 2010) (Fig.”

“Two-photon calcium imaging in L2/3 of barrel cortex in vivo (Helmchen and Denk, 2005; Wallace et al., 2008; Grewe and Helmchen, 2009) has provided additional insights into the spatiotemporal aspects of population reponses.”

“The first study that directly compared perceptual correlates with barrel column spike trains was performed more than a decade later using a variant of the task that employed a decision to drink from one of two wells instead of gap crossing as indicator response (von Heimendahl et al., 2007).”

“and L2/3 (White, 1978; Petreanu et al., 2009; Meyer et al., 2010; Oberlaender et al., 2012).”

“…to those known from other cortical systems, particularly V1 in cats and monkeys, where the cortico-cortical output of a column projects in a clustered fashion - each cluster being a dense innervation of a circumscribed column (Koralek et al., 1990; Lund et al., 1993; Douglas and Martin, 2004).”

“…thalamocortical axons in their final termination area in L4 of a single barrel (Bender et al., 2003; Harris and Woolsey, 1983; Lübke et al., 2000; Schubert et al., 2003; Staiger et al., 2004) are still prominent and are strongly affected by whisker deprivation (cf. compare normal and deprived…”

“It has been shown that texture discrimination (Carvell and Simons, 1990) as well as object localization (Knutsen et al., 2006; O’Connor et al., 2010a,b) can be performed with a single whisker suggesting that multi-whisker integration is not a strong requirement, at least for the so far tested…”

“Activation of barrel cortex follows a laminar pattern (Armstrong-James et al., 1992; Welker et al., 1993; Celikel et al., 2004).”

“Using viral approaches these protein indicators can be stably expressed in confined neuronal populations over weeks or even months (Margolis et al., 2012; O’Connor et al., 2010b).”

“At birth, the subplate mediates spindle bursts and gamma oscillations to the cortical plate (Khazipov et al., 2004; Minlebaev et al., 2007; Yang et al., 2009; Minlebaev et al., 2011).”

“…rabbit V1, S1 and M1 – identified by the waveform of their spike, the firing patterns and projection targets – clearly point to the notion that the essence of inhibitory circuits making up neocortical circuitry are likely to be captured by a similar strategy (Swadlow, 1988, 1989, 1990, 1991, 1994).”

“Whisking is hypothesized to be adaptive, adjusting movement parameters to optimize perception (Carvell and Simons, 1995).”

“The extralemniscal projection originates from multi-whisker cells in rostral SpVi (SpVir), via the barreloid tail and terminates in dysgranular S1 and in S2 (Veinante et al., 2000a; Pierret et al., 2000).”

“Two-photon calcium imaging in L2/3 of barrel cortex in vivo (Helmchen and Denk, 2005; Wallace et al., 2008; Grewe and Helmchen, 2009) has provided additional insights into the spatiotemporal aspects of population reponses.”

“Excitatory GABAergic synapses contribute initially to synchronized network activity (Owens and Kriegstein, 2002; Daw et al., 2007), but at the beginning of the second postnatal week shift to inhibitory action (Luhmann and Prince, 1991; for review see Kilb, 2011).”

“Together, ACh-related effects may increase signal to noise ratio for behaviorally relevant signals (Gil et al., 1997; Oldford and CastroAlamancos, 2003; Gulledge and Stuart, 2005; Eggermann and Feldmeyer, 2009; Gulledge and Kawaguchi, 2007; Porter et al., 1999; Christophe et al., 2002).”

“…molecular, electrophysiological and morphological properties in conjunction, many studies on neocortical inhibitory neurons came up with at least 5 main types of inhibitory neurons (Kawaguchi and Kubota, 1997; Gelman and Marin, 2010), although subdivisions have been reported frequently.”

“…of perceptual tasks that reflect specific characteristics of the conditioned stimulus (CS) in space and time (Disterhoft and Stuart, 1976; Kitzes et al., 1978; Diamond and Weinberger, 1986; Diamond and Weinberger, 1989; Recanzone et al., 1992, 1993; Schoups et al., 2001; Ghose et al., 2002).”

“subfields are generated by intracortical mechanisms (Carvell and Simons, 1988; Moore and Nelson, 1998; Schubert et al., 2001, 2003; Brecht et al., 2003; Manns et al., 2004).”

“M1 straddles what has been called the agranular medial and lateral fields (AGL and AGM, Brecht et al., 2004; Neafsey et al., 1986).”

“Arealization, the initial division of the cerebral cortex into areas during prenatal development, is essentially controlled by genes and proceeds independent from electrical activity (for review see Rash and Grove, 2006).”

“…sub-cortical pathway departs mostly from L5 large pyramids that – beyond thalamus – project as well to brainstem, reticular formation, tectum, the basal ganglia, and the cerebellar networks amongst others (see for review, Bosman et al. (2011); see also Kozloski et al., 2001 for the visual cortex).”

“4A) (Markram et al., 1997; Reyes et al., 1998; Feldmeyer et al., 1999, 2002, 2006; Petersen and Sakmann, 2000; Lübke et al., 2000, 2003; Schubert et al., 2001, 2003; Silver et al., 2003; Bureau et al., 2006; Lefort et al., 2009; Petreanu et al., 2009).”

“infer the vibrations of the whisker at the shaft, the location that directly stimulates the follicle because biomechanical transformation of tip deflection to shaft vibration is potentially complex (Neimark et al., 2003; Hartmann et al., 2003).”

“One causal factor for reduction and decorrelation of firing appears to be the upregulation of K channel expression and the concomitant decrement of input resistance of pyramidal cells (Kang et al., 1996; Maravall et al., 2004b; Waters and Helmchen, 2006; Golshani et al., 2009).”

“In addition to this disynaptic feed-forward mechanism, trisynaptic feedback inhibition via reciprocal synapse between spiny stellate and inhibitory neurons with a high connectivity ratio exists as well (Kölbl et al., 2010; Cruikshank et al., 2007; Daw et al., 2007).”

“…(i.e. response reduction with repetitive whisker stimulation) is commonly observed in the cortex (Simons, 1978, 1985; Garabedian et al., 2003; Arabzadeh et al., 2003; Hartings et al., 2003; Webber and Stanley, 2004; Khatri et al., 2004; Stüttgen and Schwarz, 2010; Sanchez-Jimenez et al.,…”

“…characterized by paired recordings – appears to be present: Bipolar-bitufted VIP cells, numerous in L2/3, sample signals from local pyramidal neurons (Porter et al., 1998; Reyes et al., 1998; Rozov et al., 2001) and target L5 pyramidal cells with their rich columnar axons (Bayraktar et al.,…”

“At this time the basic morphological features of neurons in barrel cortex are fairly well established (Zhu, 2000), but restructuring on a fine scale, e.g. higher-order branching of basal dendrites in L2/3 neurons and dendritic spine motility (Lendvai et al., 2000; Maravall et al., 2004a), or…”

“…ability to switch from burst firing to tonic firing and, secondly, on synaptic inhibition from zona incerta ventralis (ZIv), a thalamus associated nucleus receiving inputs from motor cortex and sending inhibitory inputs to POm (Bartho et al., 2002; Bokor et al., 2005; Lavallée et al., 2005).”

“Together these strong inhibitory effects in L4 are thought to set a short window for synaptic integration by excitatory L4 cells (Brecht and Sakmann, 2002a; Pinto et al., 2003; Bruno and Sakmann, 2006; Wang et al., 2010).”

“…rabbit V1, S1 and M1 – identified by the waveform of their spike, the firing patterns and projection targets – clearly point to the notion that the essence of inhibitory circuits making up neocortical circuitry are likely to be captured by a similar strategy (Swadlow, 1988, 1989, 1990, 1991, 1994).”

“Both S2 and PV receive signals from POm thalamus, with PV showing multimodal responses and providing a link to the amygdala (Shi and Cassell, 1997; Rodgers et al., 2008) and possibly also to the parahippocampal region and hippocampus (Witter et al.”

“…in VPM to L4, basal L3, L5B, and 6A of the barrel columns (Henderson and Jacquin, 1995; Lo et al., 1999) while the second lemniscal path starts from PrV multi-whisker cells and is relayed via the head of barreloids in VPM to septal columns (Veinante and Deschênes, 1999; Furuta et al., 2009b).”

“While a sub-columnar map of vibrissa motion direction was proposed to exist in L2/3 based on extracellular recordings (Andermann and Moore, 2006), no clear relationship between anatomical position and direction selectivity was found in a twophoton imaging study (Kerr et al.”

“Another contributing factor is the developmental shift of GABAergic synaptic function from excitatory to inhibitory action (for review Ben-Ari et al., 2012).”

“…period suppresses tactile inputs following at a short interval fitting the notion of a fine balance between excitatory and inhibitory signal flows (Simons, 1978, 1985; Carvell and Simons, 1988; Simons et al., 1992; Webber and Stanley, 2004; Stüttgen and Schwarz, 2008; Crochet et al., 2011).”

“The SpVic is itself under the inhibitory control of the caudalis nucleus of the trigeminal complex (SpVc) which increases sensory traffic through PrV by dis-inhibiting it from the inhibitory drive of the SpVic (Furuta et al., 2010).”

“Tactile information from individual whiskers is processed in single barrel columns in vS1 (Feldmeyer et al., 2013; Simons, 1978).”