Corticothalamic Projections Research Articles

Requirement of cannabinoid CB(1) receptors in cortical pyramidal neurons for appropriate development of corticothalamic and thalamocortical projections.

A role for endocannabinoid signaling in neuronal morphogenesis as the brain develops has recently been suggested. Here we used the developing somatosensory circuit as a model system to examine the role of endocannabinoid signaling in neural circuit formation. We first show that a deficiency in cannabinoid receptor type 1 (CB(1)R), but not G-protein-coupled receptor 55 (GPR55), leads to aberrant fasciculation and pathfinding in both corticothalamic and thalamocortical axons despite normal target recognition. Next, we localized CB(1)R expression to developing corticothalamic projections and found little if any expression in thalamocortical axons, using a newly established reporter mouse expressing GFP in thalamocortical projections. A similar thalamocortical projection phenotype was observed following removal of CB(1)R from cortical principal neurons, clearly demonstrating that CB(1)R in corticothalamic axons was required to instruct their complimentary connections, thalamocortical axons. When reciprocal thalamic and cortical connections meet, CB(1)R-containing corticothalamic axons are intimately associated with elongating thalamocortical projections containing DGLβ, a 2-arachidonoyl glycerol (2-AG) synthesizing enzyme. Thus, 2-AG produced in thalamocortical axons and acting at CB(1)Rs on corticothalamic axons is likely to modulate axonal patterning. The presence of monoglyceride lipase, a 2-AG degrading enzyme, in both thalamocortical and corticothalamic tracts probably serves to restrict 2-AG availability. In summary, our study provides strong evidence that endocannabinoids are a modulator for the proposed 'handshake' interactions between corticothalamic and thalamocortical axons, especially for fasciculation. These findings are important in understanding the long-term consequences of alterations in CB(1)R activity during development, a potential etiology for the mental health disorders linked to prenatal cannabis use.

Triadic synaptic interactions of large corticothalamic terminals in non-lemniscal thalamic nuclei of the cat auditory system

Large corticothalamic (CT) terminals, presumed to originate from cortical layer 5 pyramidal cells, are distributed predominantly in non-specific thalamic nuclei in mammals. In the auditory system, little is known about whether these CT projections participate in the synaptic aggregation referred to as the triad. We studied synaptic interactions of these terminals with neuronal elements in one of the auditory non-lemniscal thalamic nuclei, the dorsal nucleus of the medial geniculate complex (MGC), in cats. After injections of an anterograde tracer in the primary auditory cortex, areas containing labeled large terminals were examined using an electron microscope. It was revealed that a fraction of large CT terminals participated in complicated synaptic arrangements: labeled terminals making synaptic contacts with vesicle-free dendrites, probably of thalamic principal neurons, and/or vesicle-filled neuronal profiles, probably of presynaptic dendrites (PSDs) of interneurons. In reconstructions or even in single sections, we found that these synaptic connections participated in triadic arrangements. Thus, PSDs postsynaptic to the labeled CT terminals were in turn presynaptic to the vesicle-free dendrites.

Preceding Inhibition Silences Layer 6 Neurons in Auditory Cortex

A canonical feedforward circuit is proposed to underlie sensory cortical responses with balanced excitation and inhibition in layer 4 (L4). However, in another input layer, L6, sensory responses and the underlying synaptic circuits remain largely unclear. Here, cell-attached recordings in rat primary auditory cortex revealed that for the majority of L6 excitatory neurons, tonal stimuli did not drive spike responses, but suppressed spontaneous firings. Whole-cell recordings further revealed that the silencing resulted from tone-evoked strong inhibition arriving earlier than excitation. This pattern of inputs can be attributed to a parallel feedforward circuit with both excitatory and inhibitory inputs disynaptically relayed. In contrast, in the other neurons directly driven by thalamic input, stimuli evoked excitation preceding relatively weak inhibition, resulting in robust spike responses. Thus, the dichotomy of L6 response properties arises from two distinct patterns of excitatory-inhibitory interplay. The parallel circuit module generating preceding inhibition may provide a gating mechanism for conditional corticothalamic feedback.

Pathway-Specific Feedforward Circuits between Thalamus and Neocortex Revealed by Selective Optical Stimulation of Axons

Thalamocortical and corticothalamic pathways mediate bidirectional communication between the thalamus and neocortex. These pathways are entwined, making their study challenging. Here we used lentiviruses to express channelrhodopsin-2 (ChR2), a light-sensitive cation channel, in either thalamocortical or corticothalamic projection cells. Infection occurred only locally, but efferent axons and their terminals expressed ChR2 strongly, allowing selective optical activation of each pathway. Laser stimulation of ChR2-expressing thalamocortical axons/terminals evoked robust synaptic responses in cortical excitatory cells and fast-spiking (FS) inhibitory interneurons, but only weak responses in somatostatin-containing interneurons. Strong FS cell activation led to feedforward inhibition in all cortical neuron types, including FS cells. Corticothalamic stimulation excited thalamic relay cells and inhibitory neurons of the thalamic reticular nucleus (TRN). TRN activation triggered inhibition in relay cells but not in TRN neurons. Thus, a major difference between thalamocortical and corticothalamic processing was the extent to which feedforward inhibitory neurons were themselves engaged by feedforward inhibition.

Triadic synaptic interactions of large corticothalamic terminals in non-lemniscal thalamic nuclei of the cat auditory system

Large corticothalamic (CT) terminals, presumed to originate from cortical layer 5 pyramidal cells, are distributed predominantly in non-specific thalamic nuclei in mammals. In the auditory system, little is known about whether these CT projections participate in the synaptic aggregation referred to as the triad. We studied synaptic interactions of these terminals with neuronal elements in one of the auditory non-lemniscal thalamic nuclei, the dorsal nucleus of the medial geniculate complex (MGC), in cats. After injections of an anterograde tracer in the primary auditory cortex, areas containing labeled large terminals were examined using an electron microscope. It was revealed that a fraction of large CT terminals participated in complicated synaptic arrangements: labeled terminals making synaptic contacts with vesicle-free dendrites, probably of thalamic principal neurons, and/or vesicle-filled neuronal profiles, probably of presynaptic dendrites (PSDs) of interneurons. In reconstructions or even in single sections, we found that these synaptic connections participated in triadic arrangements. Thus, PSDs postsynaptic to the labeled CT terminals were in turn presynaptic to the vesicle-free dendrites.

The forkhead transcription factors, Foxp1 and Foxp2, identify different subpopulations of projection neurons in the mouse cerebral cortex

Foxp1 and Foxp2, which belong to the forkhead transcription factor family, are expressed in the developing and adult mouse brain, including the striatum, thalamus, and cerebral cortex. Recent reports suggest that FOXP1 and FOXP2 are involved in the development of speech and language in humans. Although both Foxp1 and Foxp2 are expressed in the neural circuits that mediate speech and language, including the corticostriatal circuit, the functions of Foxp1 and Foxp2 in the cerebral cortex remain unclear. To gain insight into the functions of Foxp1 and Foxp2 in the cerebral cortex, we characterized Foxp1- and Foxp2-expressing cells in postnatal and adult mice using immunohistochemistry. In adult mice, Foxp1 was expressed in neurons of layers III-VIa in the neocortex, whereas the expression of Foxp2 was restricted to dopamine and cyclic adenosine 3′,5′-monophosphate-regulated phosphoprotein, 32 kDa (DARPP-32) + neurons of layer VI. In addition, Foxp2 was weakly expressed in the neurons of layer V of the motor cortex and hindlimb and forelimb regions of the primary somatosensory cortex. Both Foxp1 and Foxp2 were expressed in the ionotropic glutamate receptor (GluR) 2/3 + neurons, and colocalized with none of GluR1, γ-aminobutyric acid, calbindin, and parvalbumin, indicating that expression of Foxp1 and Foxp2 is restricted to projection neurons. During the postnatal stages, Foxp1 was predominantly expressed in Satb2 +/Ctip2 – corticocortical projection neurons of layers III-V and in Tbr1 + corticothalamic projection neurons of layer VIa. Although Foxp2 was also expressed in Tbr1 + corticothalamic projection neurons of layer VI, no colocalization of Foxp1 with Foxp2 was observed from postnatal day (P) 0 to P7. These findings suggest that Foxp1 and Foxp2 may be involved in the development of different cortical projection neurons during the early postnatal stages in addition to the establishment and maintenance of different cortical circuits from the late postnatal stage to adulthood.

Selective Targeting of the Dendrites of Corticothalamic Cells by Thalamic Afferents in Area 17 of the Cat

Pyramidal cells of layer 6 in cat visual cortex are the source of the corticothalamic projection, and their recurrent collaterals provide substantially more excitatory synapses in layer 4 than does the thalamic input. They have predominantly simple receptive fields and can be driven monosynaptically by electrically stimulating thalamic relay cells. Layer 6 cells could thus provide a significant disynaptic amplification of the thalamic input to layer 4, particularly since their synapses facilitate, unlike the thalamic afferents whose synapses depress. However, purely geometric considerations of the relation of their dendritic trees to the thalamic input indicate that they should form a far smaller number of synapses with thalamic afferents than do the simple cells of layer 4. We thus analyzed quantitatively the thalamic input to identified corticothalamic cells by labeling the thalamic afferents and corticothalamic cells in vivo. We made a correlated light and electron microscopic study of 73 "contacts" between thalamic afferents and five corticothalamic cells. The electron microscope revealed that only 24 of the contacts identified at light microscope level were indeed synapses and, contrary to geometric predictions, virtually all were located on spines on the basal dendrites. Our quantitative estimates indicate that the corticothalamic cells form even fewer synapses with the thalamic afferents than predicted by geometric considerations and only 1/10 as many as do the layer 4 simple cells. These data strongly suggest it is the collective computation of cortical neurons, not the monosynaptic thalamic input, that determines the output of the corticothalamic cells.

Cholecystokinin action on layer 6b neurons in somatosensory cortex

Layer 6b in neocortex is a distinct sublamina at the ventral portion of layer 6. Corticothalamic projections arise from 6b neurons, but few studies have examined the functional properties of these cells. In the present study we examined the actions of cholecystokinin (CCK) on layer 6b neocortical neurons using whole-cell patch clamp recording techniques. We found that the general CCK receptor agonist CCK8S (sulfated CCK octapeptide) strongly depolarized the neurons, and this action persisted in the presence of tetrodotoxin, suggesting a postsynaptic site of action. The excitatory actions of CCK8S were mimicked by the selective CCK B receptor agonist CCK4, and attenuated by the selective CCK B receptor antagonist L365260, indicating a role for CCK B receptors. Voltage-clamp recordings revealed that CCK8S produced a slow inward current associated with a decreased conductance with a reversal potential near the K + equilibrium potential. In addition, intracellular cesium also blocked the inward current, suggesting the involvement of a K + conductance, likely K leak. Our data indicate that CCK, acting via CCK B receptors, produces a long-lasting excitation of layer 6b neocortical neurons, and this action may play a critical role in modulation of corticothalamic circuit activity.

Laminar and modular organization of prefrontal projections to multiple thalamic nuclei

The prefrontal cortex projects to many thalamic nuclei, in pathways associated with cognition, emotion, and action. We investigated how multiple projection systems to the thalamus are organized in prefrontal cortex after injection of distinct retrograde tracers in the principal mediodorsal (MD), the limbic anterior medial (AM), and the motor-related ventral anterior/ventral lateral (VA/VL) thalamic nuclei in rhesus monkeys. Neurons projecting to these nuclei were organized in interdigitated modules extending vertically within layers VI and V. Projection neurons were also organized in layers. The majority of projection neurons to MD or AM originated in layer VI (∼80%), but a significant proportion (∼20%) originated in layer V. In contrast, prefrontal neurons projecting to VA/VL were equally distributed in layers V and VI. Neurons directed to VA/VL occupied mostly the upper part of layer V, while neurons directed to MD or AM occupied mostly the deep part of layer V. The highest proportions of projection neurons in layer V to each nucleus were found in dorsal and medial prefrontal areas. The laminar organization of prefrontal cortico-thalamic projections differs from sensory systems, where projections originate predominantly or entirely from layer VI. Previous studies indicate that layer V cortico-thalamic neurons innervate through some large terminals thalamic neurons that project widely to superficial cortical layers. The large population of prefrontal projection neurons in layer V may drive thalamic neurons, triggering synchronization by recruiting several cortical areas through widespread thalamo-cortical projections to layer I. These pathways may underlie the synthesis of cognition, emotion and action.

Differences in Intrinsic Properties and Local Network Connectivity of Identified Layer 5 and Layer 6 Adult Mouse Auditory Corticothalamic Neurons Support a Dual Corticothalamic Projection Hypothesis

Intrinsic properties, morphology, and local network circuitry of identified layer 5 and layer 6 auditory corticothalamic neurons were compared. We injected fluorescent microspheres into the mouse auditory thalamus to prelabel corticothalamic neurons, then recorded and filled labeled layer 5 or layer 6 auditory cortical neurons in vitro. We observed low-threshold bursting in adult, but not juvenile, layer 5 corticothalamic neurons that was voltage and time dependent with nonlinear input-output properties, whereas adult layer 6 corticothalamic neurons demonstrated a regular spiking. Layer 5 corticothalamic neurons had larger somata, thicker apical dendrites and were more likely to have a layer 1 apical dendrite than layer 6 neurons. Using laser photostimulation, identified layer 5 corticothalamic neurons received excitatory input from a wide area of layers 2/3, 4, and 5 with widespread gamma-aminobutyric acidergic input from layer 2/3 and lower layer 5, whereas layer 6 corticothalamic neurons from the same cortical column received circumscribed excitatory input and discrete patches of inhibition derived from layer 6 of adjacent columns. These data demonstrate that layer 5 and layer 6 corticothalamic neurons receive unique sets of inputs and process them in different manners, supporting the hypothesis that layer-specific corticothalamic projections play distinct roles in information processing.

Synchrony in the Interconnected Circuitry of the Thalamus and Cerebral Cortex

The corticothalamic system is organized to play a key role in synchronizing the activities of thalamic and cortical neurons. Its synapses dominate the inputs to relay cells and to the GABAergic cells of the reticular nucleus; its organization in focused and diffuse projections promotes both coherent activity of relay neurons and the spread of activity across the cortex and thalamus. The capacity of relay neurons to operate in voltage-dependent tonic or burst mode permits corticothalamic inputs to directly excite the relay cells or indirectly inhibit them via the reticular nucleus. This enables the corticothalamic projection to synchronize high- or low-frequency oscillatory activity, respectively, in the thalamo-corticothalamic network. Differences in the subunit composition of AMPA receptors at synapses formed by branches of the same corticothalamic axon in the reticular nucleus and dorsal thalamus are an important element in the capacity of the cortex to synchronize low-frequency oscillations in the network. Intrinsic voltage-gated calcium channels of different kinds expressed in the relay neurons form a substrate for corticothalamic interactions with the relay cells that promote high- or low-frequency oscillations. Focused corticothalamic axons arising from layer VI cortical cells and diffuse corticothalamic axons arising from layer V cortical cells, in conjunction with the core and matrix cells of the dorsal thalamus, form a substrate for synchronization of widespread populations of cortical and thalamic cells during high-frequency oscillations that underlie discrete conscious events.

Cortical connections of the rat lateral posterior thalamic nucleus

Spatial processing related to directed attention is thought to be mediated by a specific cortical–basal ganglia–thalamic–cortical network in the rat. Key components of this network are associative cortical areas medial agranular cortex (AGm) and posterior parietal cortex (PPC), dorsocentral striatum (DCS), and lateral posterior (LP) thalamic nucleus, all of which are interconnected. Previously, we found that thalamostriatal projections reaching DCS arise from separate populations of neurons of the mediorostral part of LP (LPMR). The far medial LPMR (fmLPMR) terminates in central DCS, a projection area of AGm, whereas central LPMR terminates in dorsal DCS, a projection area of PPC. This represents segregated regional convergence in DCS from different sources of thalamic and cortical inputs. In the present study, thalamocortical and corticothalamic projections arising from and terminating in LPMR and neighboring thalamic nuclei were studied by anterograde and retrograde tracing techniques in order to further understand the anatomical basis of this neural circuitry. A significant finding was that within LPMR, separate neuronal populations provide thalamic inputs to AGm or PPC and that these cortical areas project to separate regions in LPMR, from which they receive thalamic inputs. Other cortical areas adjacent to AGm or PPC also demonstrated reciprocal connections with LP or surrounding nuclei in a topographic manner. Our findings suggest that the cortical–basal ganglia–thalamic network mediating directed attention in the rat is formed by multiple loops, each having reciprocal connections that are organized in a precise and segregated topographical manner.

The Thalamocortical Projection Systems in Primate: An Anatomical Support for Multisensory and Sensorimotor Interplay

Multisensory and sensorimotor integrations are usually considered to occur in superior colliculus and cerebral cortex, but few studies proposed the thalamus as being involved in these integrative processes. We investigated whether the organization of the thalamocortical (TC) systems for different modalities partly overlap, representing an anatomical support for multisensory and sensorimotor interplay in thalamus. In 2 macaque monkeys, 6 neuroanatomical tracers were injected in the rostral and caudal auditory cortex, posterior parietal cortex (PE/PEa in area 5), and dorsal and ventral premotor cortical areas (PMd, PMv), demonstrating the existence of overlapping territories of thalamic projections to areas of different modalities (sensory and motor). TC projections, distinct from the ones arising from specific unimodal sensory nuclei, were observed from motor thalamus to PE/PEa or auditory cortex and from sensory thalamus to PMd/PMv. The central lateral nucleus and the mediodorsal nucleus project to all injected areas, but the most significant overlap across modalities was found in the medial pulvinar nucleus. The present results demonstrate the presence of thalamic territories integrating different sensory modalities with motor attributes. Based on the divergent/convergent pattern of TC and corticothalamic projections, 4 distinct mechanisms of multisensory and sensorimotor interplay are proposed.

Fast awakening from minimally conscious state with apomorphine

Background: Traumatic brain injury (TBI) can induce long-term severe disorders of consciousness. Evidence suggests an underlying dopaminergic deficit. Dopamine agonists may therefore play an important role in recovery of consciousness.Objective: To explore the response to continuous subcutaneous administration of apomorphine in a patient who had remained in minimally conscious state for 104 days and to evaluate the anatomical substrate of the effect.Design: A prospective, open-label, daily treatment, dose-escalation single case clinical study, with retrospective diffusion tensor image (DTI) evaluation.Results: On the fist day of treatment, the patient was able to move his limbs on command and answer yes/no questions which had not been the case prior to apomorphine administration. Subsequently there was a full recovery of consciousness and substantial functional recovery that was sustained even after apomorphine discontinuation. At the highest dose, mild dyskinesias were observed. These resolved with a lowering of the dose. DTI demonstrated a decrease of thalamocortical and corticothalamic projections in this MCS patient compared to normal volunteers.Conclusion: Although this is an open-label single-patient case report, the data are consistent with the theory that a dopaminergic deficit underlies MCS and that it may be overcome with apomorphine administration.

Task-Dependent Modulation of Medial Geniculate Body Is Behaviorally Relevant for Speech Recognition

SummaryRecent work has shown that responses in first-order sensory thalamic nuclei are modulated by cortical areas [1–5]. However, the functional role of such corticothalamic modulation and its relevance for human perception is still unclear. Here, we show in two functional magnetic resonance imaging (fMRI) studies that the neuronal response in the first-order auditory thalamus, the medial geniculate body (MGB), is increased when rapidly varying spectrotemporal features of speech sounds are processed, as compared to processing slowly varying spectrotemporal features of the same sounds. The strength of this task-dependent modulation is positively correlated with the speech recognition scores of individual subjects. These results show that task-dependent modulation of the MGB serves the processing of specific features of speech sounds and is behaviorally relevant for speech recognition. Our findings suggest that the first-order auditory thalamus is not simply a nonspecific gatekeeper controlled by attention [6]. Together with studies in nonhuman mammals [4, 5], our findings imply a mechanism in which the first-order auditory thalamus, possibly by corticothalamic modulation, reacts adaptively to features of sensory input.

Localization of prolyl oligopeptidase in the thalamic and cortical projection neurons: A retrograde neurotracing study in the rat brain

Prolyl oligopeptidase (POP) is a serine endopeptidase which hydrolyses proline-containing peptides shorter than 30-mer. POP is believed to be associated with cognitive functions via neuropeptide cleavage. POP has been also connected to the inositol 1,4,5-triphosphate (IP3) signalling but the effects of POP-inhibition to the IP3 accumulation in vivo are still unclear. However, little is known about the physiological role of POP in the brain. We have previously found that in the rat brain POP was specifically expressed in the pyramidal neurons of the cerebral cortex, particularly in the primary motor and somatosensory cortices, and corresponding projection areas in thalamus. Using a retrograde neurotracer we have now visualized the localization of POP in thalamocortical and corticothalamic projection neurons in ventrobasal complex and medial geniculate nucleus of thalamus and somatosensory/motor and auditory cortices. We observed that both in thalamus and cortex over 50% of projection neurons contained POP. These results support the hypothesis that POP is involved in thalamocortical and corticothalamic signal processing. We also propose, based on our neuroanatomical findings and literature, that POP may take part in the thalamocortical oscillations by interacting with IP3 signalling in cells.

Topography in the projections of lateral posterior thalamus with cingulate and medial agranular cortex in relation to circuitry for directed attention and neglect

In the rat, the lateral posterior thalamic nucleus (LP) has reciprocal connections with areas of the cortex and the striatum involved in directed attention and its dysfunctional counterpart, contralateral neglect. It has also been shown that the medial portion of the mediorostral part of LP (mLPMR) is of special interest because it has connections with the dorsocentral striatum, a key node in this circuitry. In the present study we used neuroanatomical tracers to map the specific connections and topography of LP with the anterior cingulate cortex (ACC) and medial agranular cortex (AGm). We primarily used Alexa Fluor conjugates of the retrograde tracer cholera toxin subunit B, and injected two different colored conjugates into ACC and AGm in the same animal in order to directly compare the differential topography of the thalamocortical connections of mLPMR. The bidirectional tracer, dextran amine, was also used to examine anterograde corticothalamic projections of AGm and ACC. We found that mLPMR consists of two distinct groups of neurons, with the more dorsal group projecting to ACC and the more ventral group projecting to AGm. This is mirrored by a similar corticothalamic topography. These findings suggest that the ventral mLPMR is specifically associated with AGm and dorsocentral striatum, while dorsal mLPMR is associated with ACC. They also suggest that ACC may play a role in the circuitry for directed attention and contralateral neglect, as it is known to do in humans.

Contralateral corticothalamic projections from MI whisker cortex: Potential route for modulating hemispheric interactions

Rat whisking behavior is characterized by high amounts of bilateral coordination in which whisker movements on both sides of the face are linked. To elucidate the neural substrate that might mediate this bilateral coordination, neuronal tracers were used to characterize the bilateral distribution of corticothalamic projections from primary motor (MI) cortex. Some rats received tracers in the MI whisker region, whereas others received tracers in the MI forepaw region. The MI whisker region projects bilaterally to the anteromedial (AM), ventromedial (VM), and ventrolateral (VL) nuclei, and to parts of the intralaminar nuclei. By contrast, the MI forepaw region sends virtually no projections to the contralateral thalamus. Consistent with these findings, bilateral injections of different tracers into the MI whisker region of each hemisphere produced tracer overlap on both sides of the thalamus. Furthermore, MI whisker projections to the contralateral thalamus terminate in close proximity to the thalamocortical neurons that project to the MI whisker region of that contralateral hemisphere. The terminal endings of the contralateral corticothalamic projections contain small synaptic varicosities and other features that resemble the modulator pathways described for other corticothalamic projection systems. In addition, tracer injections into AM, VM, and VL revealed dense clusters of labeled neurons in layer VI of the medial agranular (Agm) zone, which corresponds to the MI whisker region. These results suggest that projections from the MI whisker region to the contralateral thalamus may modulate the callosal interactions that are presumed to play a role in coordinating bilateral whisking behavior.

Rac1 in cortical projection neurons is selectively required for midline crossing of commissural axonal formation

Rac1 is a member of Rho family GTPases and regulates multiple cellular functions through actin cytoskeleton reorganization. During cerebral corticogenesis, Rac1 has been assumed to be involved in neuronal migration, neurite formation, polarization and axonal guidance. Here we show the specific role of Rac1, regulating midline crossing of commissural axons during cortical development by using cortex-restricted Rac1-knockout mice. In the knockout mice, Rac1 was eliminated from the beginning of corticogenesis exclusively in the dorsal telencephalon where progenitors of cortical projection neurons are located. Cortical lamination was distorted only mildly in the knockout mice, being preserved with six layers of neurons. However, cortex-restricted Rac1 deletion exhibited striking agenesis of commissural axons including the corpus callosum and anterior commissure without affecting other corticofugal axons including corticospinal and corticothalamic projections. Of note, the commissural axons of the knockout mice were potent in extending their process, but failed to cross the midline. Therefore, these findings indicate that Rac1 specifically controls the midline crossing of the commissural fibers, but not axonal formation of corticospinal or corticothalamic fibers during cortical development.

Vibrissal responses of thalamic cells that project to the septal columns of the barrel cortex and to the second somatosensory area.

The rodent somatosensory cortex contains barrel-related and septa-related circuits representing two separate streams of vibrissa information processing that differ in their response patterns and anatomical connections. Whereas barrel-related circuits process lemniscal inputs that transit through the thalamic barreloids, septa-related circuits process paralemniscal inputs and inputs that are relayed through the ventral lateral part of the ventral posterior medial nucleus (VPMvl). Septa-projecting thalamic afferents also target the secondary somatosensory cortical area. Although a number of studies have examined response properties in the lemniscal pathway, and demonstrated that barreloids receive feedback from specific sets of corticothalamic and reticular thalamic neurons, such information is currently lacking for the VPMvl. In the present study, we show that in sharp contrast to the relay cells of the barreloids VPMvl neurons exhibit large multiwhisker receptive fields that are independent of input from the principal trigeminal nucleus. Results also suggest that the topography of receptive fields and response properties in VPMvl rely on converging input from neurons of the interpolaris trigeminal nucleus. Tracer injection and single-cell labeling further reveal that the VPMvl receives input from specific populations of reticular thalamic and corticothalamic neurons. Together, these results confirm the status of the VPMvl as a thalamic relay of an independent parallel pathway of vibrissa information processing. They further indicate that a sensory pathway does not merely consist on a three-neuron chain that links the vibrissae to the cerebral cortex, but that it also involves specific sets of topographically related corticothalamic and reticular thalamic projections.