Neonatal whisker removal in rats stabilizes a transient projection from the auditory thalamus to the primary somatosensory cortex

A normally transient cross-modal thalamocortical projection from the magnocellular subdivision of the medial geniculate nucleus (MGm) to the primary somatosensory (SI) cortex of rats was found to remain unchanged throughout adulthood following unilateral removal of whiskers in newborn animals. The normal MGm projection to the auditory cortex is not lost in these neonatally whisker-deprived adults rats but some of the MGm neurons send collaterals to both primary auditory and SI cortices. Parallel electrophysiological experiments demonstrated the multimodal character of some MGm neurons, since they responded to both auditory and cutaneous stimulation. These results suggest that the areal distribution in the cortex of thalamocortical projections arising from a multimodal thalamic nucleus, such as the MGm, may be determined during early postnatal development by the normal flow of sensory information from the periphery to the thalamus and that an early postnatal somatosensory deprivation may prevent the normal withdrawal of a cross-modal projection from the MGm to the SI.     

Corticofugal influence upon cat thalamic ventrobasal complex

The influence of somatosensory cortex upon transmission through its specific thalamic relay nucleus, the ventrobasal complex (VB), was studied in the paralyzed, unanesthetized cat. The medial lemniscus was electrically stimulated, and evoked responses were recorded from the thalamic radiations projecting respectively to the first and second somatosensory cortex (SITR) and SIITR) and from the pial surface of SI and SII. Cortical influence was assessed by cooling so as to produce a functional and reversible ablation. This technique avoided the ambiguity usually associated with direct electrical stimulation of cortex. Such stimulation, as used by several other authors, may lead to uncontrolled transsynaptic effects upon VB neurons via antidromic activation of thalamocortical fibers and resultant invasion of VB recurrent collaterals.Cooling of SI and SII together resulted in greatly augmented evoked activity in thalamocortical projection fibers concurrent with cessation of cortical EEG at an intracortical temperature of 21 °C. This is interpreted to mean that under normal conditions the somatosensory cortex exhibits a net tonic inhibitory influence upon VB transmission. The same results were obtained in thecerveau isolé preparation; thus, the net cortical inhibitory influence could not be mediated by the brain stem reticular formation, but must be a direct corticofugal influence exerted upon VB. Antidromic activation of ML terminals in VB was unaltered by cooling of somatosensory cortex. This suggests that the corticofugal inhibition is mediated via a postsynaptic mechanism, rather than a presynaptic one.Cooling SI alone resulted in increased responses in SITR but not in SIITR. On the other hand, separate cooling of SII resulted in increased responses in both SITR and SIITR. This suggests that each somatosensory receiving area exerts inhibitory control over its own thalamic input but that, in addition, SII exerts control over SI input.     

Corticofugal influences on thalamic neurons during nociceptive transmission in awake rats

Pain is a multidimensional phenomenon and processed in a neural network. The supraspinal, brain mechanisms are increasingly recognized in playing a major role in the representation and modulation of pain. The aim of the current study is to investigate the functional interactions between cortex and thalamus during nociceptive processing, by observing the pain-related information flow and neuronal correlations within thalamo-cortical pathways. Pain-evoked, single-neuron activity was recorded in awake Sprague-Dawley rats with a Magnet system. Eight-wire microarrays were implanted into four different brain regions, i.e., the primary somatosensory (SI) and anterior cingulate cortex (ACC), as well as ventral posterior (VP) and medial dorsal thalamus (MD). Noxious radiant heat was delivered to the rat hind paws on the side contralateral to the recording regions. A large number of responsive neurons were recorded in the four brain areas. Directed coherence analysis revealed that the amount of information flow was significantly increased from SI cortex to VP thalamus following noxious stimuli, suggesting that SI cortex has descending influence on thalamic neurons during pain processing. Moreover, more correlated neuronal activities indicated by crosscorrelation histograms were found between cortical and thalamic neurons, with cortical neurons firing ahead of thalamic units. On basis of the above findings, we propose that nociceptive responses are modulated by corticothalamic feedback during nociceptive transmission, which may be tight in the lateral pathway, while loose in the medial pathway.     

Corticothalamic modulation on formalin-induced change of VPM thalamic activities

Spontaneous activities of single cells were extracellularly recorded in ventral posterior medial (VPM) thalamus of anesthetized rats to characterize the corticothalamic modulation on formalin-induced changes of spontaneous thalamic firing. Formalin injected into the peripheral receptive field, dose-dependently induced the reversible facilitation of spontaneous activities of VPM. However, when the primary somatosensory (SI) cortex was inactivated by muscimol, the pattern of formalin-induced changes of VPM firing was altered. This altered responsiveness included both first and second phase of facilitated spontaneous activities. Bicuculline infused into SI cortex did not alter the pattern of formalin-induced thalamic changes. These results suggest that the pain reactivity of VPM thalamus may be modulated by cortex via corticothalamic pathway during the generation of inflammatory pain.     

Changes in the thalamocortical connectivity during anesthesia-induced transitions in consciousness

Thalamocortical networks play an important role in information integration during consciousness. However, little is known about how the information flows between the thalamus and the cortex are affected by a loss of consciousness. To investigate this issue, we analyzed effective connectivity between the cortex and the thalamus in animals during anesthesia-induced transitions. By recording the electroencephalogram from the primary motor and the primary somatosensory cortex and by recording local field potentials from the ventral lateral and the ventrobasal thalamic nuclei, we evaluated changes in the conditional Granger causality between cortical and thalamic electrical activity as mice gradually lost consciousness from the use of anesthesia (ketamine/xylazine). The point of loss of consciousness was indicated by a moment of loss of movement that was measured using a head-mounted motion sensor. The results showed that 65% of the thalamocortical information flows were changed by anesthesia-induced loss of consciousness. Specifically, the effective connectivity between the cortex and the ventral lateral thalamus was altered such that the primary motor and the primary somatosensory cortex Granger-caused the ventral lateral thalamus before loss of consciousness whereas the ventral lateral thalamus Granger-caused the primary motor cortex and the primary somatosensory cortex after loss of consciousness. In contrast, the primary somatosensory cortex consistently Granger-caused the ventrobasal thalamus, regardless of the loss of consciousness. These results suggest how information flows change across the thalamocortical network during transitions in consciousness.     

Cortical origin of functional recovery in the somatosensory cortex of the adult mouse after thalamic lesion

To study the degree and time course of the functional recovery in the somatosensory cortex (SI) after an excitotoxic lesion in the adult mouse thalamus, metabolic activity was determined in SI at various times points post-lesion. Immediately after the lesion, metabolic activity in the thalamically deafferented part of SI was at its lowest value but increased progressively at subsequent time points. This was seen in all cortical layers; however, layers I and Vb recovered more rapidly than layers II, III, IV, Va and VI. Removal of the mystacial whiskers corresponding to the deafferented area, 5 weeks after cortical recovery, produced a subsequent 32% drop in metabolic activity, demonstrating peripheral sensory activation of this part of the cortex. Tracing experiments revealed that the deafferented cortex did not receive a novel thalamic input but that cortico-cortical and contralateral barrel cortex projections to this area were reinforced. We conclude that the cortical functional recovery after a thalamic lesion is, at least partially, due to modified cortico-cortical and callosal projections to the deafferented cortical area.     

Vibrissae tactile stimulation: (14C) 2-deoxyglucose uptake in rat brainstem, thalamus, and cortex

The right mystacial vibrissae of awake, adult rats were stroked at 4-6 times/second and brain regions which increased (14C) 2-deoxyglucose (2DG) uptake were mapped autoradiographically. The ventral parts of the ipsilateral spinal trigeminal nuclei pars caudalis (Sp5c), pars interpolaris (Sp5i), pars oralis (Sp5o), and the principal trigeminal sensory (Pr5) nuclei were activated. The lateral part of the ipsilateral facial (VII) nucleus (the region which innervates the vibrissae muscles) was also activated possibly via excitatory, trigeminal (Sp5c, Sp5i, Sp5o, Pr5) sensory afferents. A number of regions were activated contralateral to the sensory stimulus. Discrete patches of (14C) 2DG uptake occurred in deep layers of the superior colliculus (SCsgp). Dorsolateral and dorsomedial parts of the ventrobasal nucleus (VB), and posterior, dorsolateral parts of the reticular nucleus (R) of thalamus were activated, along with broad portions of the primary somatosensory cortex (SI) and second somatosensory cortex (SII). Though all layers of SI and SII cortex increased 2DG uptake, VB thalamic afferents to layers IV and Vc-Vla presumably accounted for the greater activation of these cortical layers during repetitive sensory stimulation of the vibrissae (RSSV). Activation of the above structures fits well with known anatomical data. However, the pattern of activation during RSSV was very different from that previously described during vibrissae motor cortex stimulation (VMIS). RSSV and VMIS both produced similar repetitive movements of all the mystacial vibrissae. However, only a few overlapping brain regions were activated during both RSSV and VMIS. These RSSV-VMIS overlap zones included Sp5o; rostral Sp5i; lateral VII; SCsgp; ventrobasal-posteromedial and ventrobasal-ventrolateral zones in thalamus; and a rostral region of SI probably anterior to the Woolsey vibrissae barrelfield in the dysgranular somatosensory (SI) cortex. Since RSSV and VMIS would both be expected to activate vibrissae proprioceptors, we have hypothesized that vibrissae proprioceptive input was processed in part in the RSSV-VMIS overlap zones. Convergence of motor-sensory inputs and other types of processing could have also occurred in these overlap zones.     

Reduced sensorimotor inhibition in the ipsilesional motor cortex in a patient with chronic stroke of the paramedian thalamus.

OBJECTIVE: Unilateral or bilateral paramedian infarction in the region of the thalamus and upper midbrain may lead to hypersomnia. To determine whether unilateral infarction of the paramedian thalamus leads to changes in excitability of ipsilesional primary motor hand area (M1). METHODS: We describe a patient with chronic stroke of the right dorsomedian and intralaminar thalamic nuclei, who suffered from mild persistent hypersomnia. We studied the excitability of the right and left M1 with transcranial magnetic stimulation (TMS) in the patient, and in 10 healthy controls. RESULTS: In contrast to healthy controls, contralateral electrical stimulation of the median nerve failed to induce short-latency afferent inhibition (SAI) in the ipsilesional M1. Other measures of corticomotor excitability and somatosensory evoked potentials were normal. CONCLUSIONS: The selective loss of ipsilateral SAI in a patient with paramedian thalamic stroke suggests that during wakefulness, the intact paramedian thalamus facilitates the excitability of intracortical inhibitory circuits, which process thalamocortical sensory inputs in the ipsilateral M1. This preliminary finding suggests that measurements of SAI may provide a means of probing the integrity of some neural pathways, which are involved in the control of wakefulness and arousal. SIGNIFICANCE: In addition to the established role of the paramedian thalamus in arousal and memory, our observation suggests that thalamocortical projections from the paramedian thalamus contribute to the integration of sensory input at the cortical level during wakefulness.     

Alertness opens the effective flow of sensory information through rat thalamic posterior nucleus

Behavioural reactions to sensory stimuli vary with the level of arousal, but little is known about the underlying reorganization of neuronal networks. In this study, we use chronic recordings from the somatosensory regions of the thalamus and cortex of behaving rats together with a novel analysis of functional connectivity to show that during low arousal tactile signals are transmitted via the ventral posteromedial thalamic nucleus (VPM), a first‐order thalamic relay, to the primary somatosensory (barrel) cortex and then from the cortex to the posterior medial thalamic nucleus (PoM), which plays a role of a higher‐order thalamic relay. By contrast, during high arousal this network scheme is modified and both VPM and PoM transmit peripheral input to the barrel cortex acting as first‐order relays. We also show that in urethane anaesthesia PoM is largely excluded from the thalamo‐cortical loop. We thus demonstrate a way in which the thalamo‐cortical system, despite its fixed anatomy, is capable of dynamically reconfiguring the transmission route of a sensory signal in concert with the behavioural state of an animal.     

Axonal trajectories between mouse somatosensory thalamus and cortex

An in vitro brain slice preparation has been used to label fibers connecting the somatosensory thalamus and cortex of the mouse. In 400-800-micron brain slices, the pathway between the ventrobasal complex and somatosensory cortex was labeled under direct vision with horseradish peroxidase crystals (HRP), HRP-Nonidet P-40 (NP40) detergent chips, or a solution of HRP/dimethylsulfoxide. Thalamocortical and corticofugal fibers are organized into a plexiform system of bundles that appears to be fairly constant from animal to animal. Bundles of fibers projecting from the ventrobasal complex course between regularly spaced groups of thalamic neurons. Thalamocortical axons do not invariably leave the thalamus via the fiber bundle closest to the perikarya. Thus, nearest-neighbor relationships are abolished before these axons have even left the thalamus. The axon bundles traverse the thalamic reticular nucleus lateral to the complex. The axons then rotate about one another, analogous to the coiling of strands in rope about a central axis. This accounts for the well known 180 degrees rotation in the mediolateral direction between thalamic and cortical maps. Laterally, fiber bundles converge and diverge within the internal capsule so that nearest-neighbor relationships are lost. Individual thalamocortical axons do not bifurcate proximal to the subcortical white matter. After single bundles of fibers reach a point just below the subcortical white matter, their individual fibers diverge widely. Within the subcortical white matter most afferent fibers make a small dorsally concave loop prior to taking one of two possible courses: some of the fibers ascend directly into the overlying cortex usually angled towards the dorsal surface of the brain; other fibers run in the subcortical white matter for variable distances prior to ascending into cortex. Within somatosensory cortex, smooth axons branch near their terminals in layers IV and VI. Axonal terminal and branching patterns of these axons within somatosensory cortex are similar to those found in in vivo preparations. Most axons are smooth, but other axons are beaded. Some beaded axons project to layer I. Corticofugal fibers are labeled. Fibers leaving somatosensory cortex have an angle of descent opposite to the angle of ascent for afferent fibers, and are often fasciculated in the cortex and subcortical white matter. Within the subcortical white matter efferent fibers often loop in a direction opposite to that of afferent fibers. Corticofugal fibers occasionally give off a collateral corticostriatal branch within the internal capsule.(ABSTRACT TRUNCATED AT 400 WORDS)     

Relations between cortical and thalamic cellular activities during absence seizures in rats

In a rat model of generalized absence epilepsies (Genetic Absence Epilepsy Rats from Strasbourg, GAERS), multiunit activity was recorded simultaneously at different sites of the thalamocortical system under neurolept anaesthesia (fentanyl-droperidol). Under these conditions, bilaterally synchronized spike-and-wave-discharges (SWDs) occurred spontaneously on the electroencephalogram (EEG) that were in principle identical to those reported earlier from unanaesthetized preparations. The generation of SWDs on the EEG was associated with spike-concurrent, rhythmic burst-like activity in (mono-)synaptically connected regions of specific (somatosensory) thalamic regions and layers IV/V of the somatosensory cortex, and the reticular thalamic nucleus. Precursor activity was typically recorded in cortical units, concomitant with ‘embryonic’ SW seizures on the EEG, before the paroxysm was evident on the gross EEG and in the thalamus. On average, SWD-correlated activity in layers IV/V of the somatosensory cortex started significantly earlier than correlated burst-like firing in reticular and in ventrobasal thalamic neurons. Cellular peak firing in thalamus and cortex during bilaterally synchronized SWDs was related to the spike component on the gross EEG with the temporal rank order ventroposteromedial > ventrolateral ≥ ventroposterolateral thalamic > > rostral reticular thalamic nuclei ≥ cortex (layers IV/V) = caudal reticular thalamic nucleus. A spike-related depression and wave-related increase in firing was recorded in anteroventral ventrolateral thalamic areas, presumably reflecting their peculiar anatomical arrangement within the thalamus. These results from an in vivo preparation with intact synaptic connections that spontaneously produces SWDs indicate that SWDs spread within the thalamocortical network, involving short and long delays. The order of concurrent rhythmic firing observed in thalamocortical circuits during SW seizures are supportive of the hypothesis that the processes of rhythmogenesis recruit local thalamic networks, while cortical mechanisms appear to synchronize rhythmic activities on a larger spatiotemporal scale, thereby providing an important contribution to the generalization of epileptiform activity and expression of SWDs on the EEG.     

Systemically administered cocaine alters stimulus-evoked responses of thalamic somatosensory neurons to perithreshold vibrissae stimulation

Previous studies have shown that systemically administered cocaine can transiently alter responses of primary somatosensory cortical neurons to threshold level stimulation of peripheral receptive fields. The goal of the present investigation was 2-fold: (1) characterize the effects of systemic cocaine on stimulus-evoked responses of the ventral posterior medial (VPM) thalamic neurons which relay somatosensory information to the cortex and (2) determine the time course and magnitude of changes in monoamine levels within the somatosensory thalamus following systemic administration of cocaine. Extracellularly recorded responses of single VPM thalamic neurons to whisker stimulation were monitored before and after cocaine administration in halothane anaesthetized rats. Each cell was first characterized by assessing its response profile to a range of perithreshold level deflections of the optimal whisker on the contralateral face. Drug effects on stimulus-response curves, response magnitude and latency were determined from quantitative analysis of spike train data. The results indicate that cocaine elicits a predictable augmentation or attenuation of the sensory response magnitude, with the direction of the change inversely related to the initial magnitude of the stimulus-evoked discharge. In addition, cocaine consistently reduced the response time of somatosensory thalamic neurons to peripheral receptive field stimulation. At the same dose and over the same time period, cocaine also produced marked elevation of norepinephrine and serotonin levels within the ventrobasal thalamus, as determined by in vivo microdialysis. These results suggest that cocaine-induced increases in norepinephrine and serotonin are responsible for drug-related modulation of the transfer of sensory signals through primary thalamocortical relay circuits.     

The effect of etomidate on sensory transmission in the dorsal column pathway in the urethane-anaesthetized rat.

The effect of Etomidate, a general anaesthetic, on sensory afferent transmission was measured in the dorsal column pathway in urethane-anaesthetized rats. Extracellular recordings were made of peripherally evoked responses by single cells in the cuneate nucleus, ventroposterolateral nucleus of the thalamus and laminae IV-VI of the primary somatosensory cortex. Cortical mass responses were also recorded. In further experiments, cortical mass responses were evoked antidromically by stimulation in the pyramidal tract. The effect of incremental administration of Etomidate on evoked responses was recorded. These results are compared with the previously reported effects of urethane, a 'conventional' anaesthetic. Etomidate did not alter cuneate or ventroposterolateral thalamic cell responses but it caused a dose-dependent reduction in cortical cell responsiveness. It failed to alter antidromically evoked cortical mass responses. Etomidate differs from the majority of anaesthetics, which act in the thalamus, and appears to cause perturbation at the cortical level.     

Development of cortical maps: perspectives from the barrel cortex.

One approach to examining how higher sensory, motor, and cognitive faculties emerge in the neocortex is to elucidate the underlying wiring principles of the brain during development. The mammalian neocortex is a layered structure generated from a sheet of proliferating ventricular cells that progressively divide to form specific functional areas, such as the primary somatosensory (S1) and motor (M1) cortices. The basic wiring pattern in each of these functional areas is based on a similar framework, but is distinct in detail. Functional specialization in each area derives from a combination of molecular cues within the cortex and neuronal activity-dependent cues provided by innervating axons from the thalamus. One salient feature of neocortical development is the establishment of topographic maps in which neighboring neurons receive input relayed from neighboring sensory afferents. Barrels, which are prominent sensory units in the somatosensory cortex of rodents, have been examined in detail, and data suggest that the initial, gross formation of the barrel map relies on molecular cues, but the refinement of this topography depends on neuronal activity. Several excellent reviews have been published on the patterning and plasticity of the barrel cortex and the precise targeting of ventrobasal thalamic axons. In this review, the authors will focus on the formation and functional maturation of synapses between thalamocortical axons and cortical neurons, an event that coincides with the formation of the barrel map. They will briefly review cortical patterning and the initial targeting of thalamic axons, with an emphasis on recent findings. The rest of the review will be devoted to summarizing their understanding of the cellular and molecular mechanisms underlying thalamocortical synapse maturation and its role in barrel map formation.     

Thalamocortical dysfunction and thalamic injury after asphyxial cardiac arrest in developing rats

Global hypoxia-ischemia interrupts oxygen delivery and blood flow to the entire brain. Previous studies of global brain hypoxia-ischemia have primarily focused on injury to the cerebral cortex and to the hippocampus. Susceptible neuronal populations also include inhibitory neurons in the thalamic reticular nucleus. We therefore investigated the impact of global brain hypoxia-ischemia on the thalamic circuit function in the somatosensory system of young rats. We used single neuron recordings and controlled whisker deflections to examine responses of thalamocortical neurons to sensory stimulation in rat survivors of 9 min of asphyxial cardiac arrest incurred on postnatal day 17. We found that 48-72 h after cardiac arrest, thalamocortical neurons demonstrate significantly elevated firing rates both during spontaneous activity and in response to whisker deflections. The elevated evoked firing rates persist for at least 6-8 weeks after injury. Despite the overall increase in firing, by 6 weeks, thalamocortical neurons display degraded receptive fields, with decreased responses to adjacent whiskers. Nine minutes of asphyxial cardiac arrest was associated with extensive degeneration of neurites in the somatosensory nucleus as well as activation of microglia in the reticular nucleus. Global brain hypoxia-ischemia during cardiac arrest has a long-term impact on processing and transfer of sensory information by thalamic circuitry. Thalamic circuitry and normalization of its function may represent a distinct therapeutic target after cardiac arrest.     

Protracted expression of serotonin transporter and altered thalamocortical projections in the barrelfield of hypothyroid rats

In humans, thyroid hormone deficiency during development causes severe neurological diseases but the underlying mechanisms are unclear. We have examined the effects of thyroid hormones on the development of somatosensory thalamocortical projections, by inducing hypothyroidism in rats by methimazole treatment at embryonic day 13 and subsequent thyroidectomy at postnatal day 6 (P6). Initial development of the thalamocortical projections and their tangential and laminar patterning were similar in normal and hypothyroid rats from birth to P4. The tangential spread of the thalamocortical arbors is reduced in hypothyroid rats after P4, paralleling the overall cortical atrophy. Anterograde tracing and single axon reconstructions indicate that thalamic afferents reached layer IV but that they had fewer and shorter branches, with a 42% reduction in the number of boutons. The transient serotonin (5-HT) immunostaining and 5-HT transporter (5-HTT) expression were both prolonged by 5 days in hypothyroid rats. This does not reflect a delayed maturation of the thalamus because other transiently expressed genes such as the vesicular monoamine transporter and the 5-HT1B receptor are not modified. Protracted 5-HTT expression also occurred in other areas with transient expression, but no changes were observed in the raphe nuclei where the 5-HTT is expressed permanently. Thus, thyroid hormones appear to be important in regulating the extinction of the 5-HTT in nonserotoninergic neurons. The transient stabilization of 5-HT reuptake in hypothyroid rats could affect the growth of thalamic axons. Our data stress the importance of maternal and foetal thyroid hormones for the normal development of sensory systems.     

Localization of the Origin of Self-Sustained Afterdischarges (SSADs) in the Rat

The genesis of the thalamocortical self-sustained afterdischarge (SSAD) composed of spike-and-wave (S + W) rhythm was studied in adult male albino rats. Under control conditions, rhythmic electrical stimulation of the specific somatosensory nucleus of the thalamus always elicited type S + W SSAD. An electrolytic lesion of the nonspecific thalamic nuclei did not prevent generation of type S + W SSAD, while stimulation of the ventrobasal complex evoked both type S + W SSAD and another type of SSAD composed of large waves with superimposed fast activity. Elimination of the cortex (by suction or spreading depression) ipsilateral to the stimulated thalamus completely suppressed any possibility of the formation of type S + W SSAD; elimination of the contralateral cortex did not affect it. Our results suggest that the cortex is the decisive factor in the genesis of S + W rhythm, while the thalamus markedly influences the conditions of its formation.     

Formation of specific afferent connections in organotypic slice cultures from rat visual cortex cocultured with lateral geniculate nucleus.

The development of the cerebral cortex involves the specification of intrinsic circuitry and extrinsic connections, the pattern of inputs and outputs. To investigate the development of a major afferent input to the cortex, we studied the formation of thalamocortical connections in an organotypic culture system. Slices from the lateral thalamus of young rats were cocultured with slices from the visual cortex. Thalamocortical projections in vitro were examined anatomically with fluorescent dyes and physiologically with electrophysiological and optical recording techniques. Axons emerged from thalamic explants radially in all directions. The outgrowth of thalamic fibers and the course of the axonal trajectories were not influenced by the presence of the cocultured cortex. Only those thalamic axons that happened to grow toward the cortical slices invaded their target tissue. Thalamocortical projection cell in vitro had the characteristic morphology of thalamic relay neurons. Cells with the morphology of interneurons were present in thalamic explants, but these neurons did not project to the cocultured cortex. Thalamocortical axons in vitro terminated in their appropriate cortical target layer, formed axonal arbors, and made functional synaptic contacts. Such specific connections between thalamic neurons and their cortical target cells were established regardless of whether thalamocortical axons invaded the cortex from the white matter side or from the pial surface. These results suggest that thalamic projection neurons have an innate mechanism that allows them to recognize their cortical target cells. Thus, intrinsic factors play a significant role in the laminar specification of cortical connections during development.     

Dynamic neuronal responses in cortical and thalamic areas during different phases of formalin test in rats

Although formalin-induced activity in primary afferent fibers and spinal dorsal horn is well described, the forebrain neural basis underlying each phase of behavior in formalin test has not yet been clarified. The present study was designed to investigate the cortical and thalamic neuronal responses and interactions among forebrain areas during different phases after subcutaneous injection of formalin. Formalin-induced neuronal activities were simultaneously recorded from primary somatosensory cortex (SI), anterior cingulate cortex (ACC) and medial dorsal (MD) and ventral posterior (VP) thalamus during different phases (i.e., first phase, interphase, second phase and third recovery phase starting from 70 min after injection) of formalin test, using a multi-channel, single-unit recording technique. Our results showed that, (i) unlike the responses in primary afferent fibers and spinal dorsal horn, many forebrain neurons displayed monophasic excitatory responses in the first hour after formalin injection, except a small portion of neurons which exhibited biphasic responses; (ii) the response patterns of many cortical and thalamic neurons changed from excitatory to inhibitory at the end of the second phase; (iii) the direction of information flow also changed dramatically, i.e., from cortex to thalamus and from the medial to the lateral pathway in the first hour, but reversed in phase 3. These results indicate that the changes of activity pattern in forebrain networks may underlie the emerging and subsiding of central sensitization-induced pain behavior in the second phase of formalin test.     

Long-term trans-synaptic glial responses in the human thalamus after peripheral nerve injury.

Limb denervation leads to reorganization of the representational zones of the somatosensory cortex. Using [11C](R)-PK11195, a sensitive in vivo marker of glial cell activation, and PET, we provide first evidence that limb denervation induces a trans-synaptic increase in [11C](R)-PK11195 binding in the human thalamus but not somatosensory cortex: these brain structures appeared morphologically normal on magnetic resonance imaging (MRI). The increased thalamic signal was detectable many years after nerve injury, indicating persistent reorganization of the thalamus. This glial activation, beyond the first-order projection area of the injured neurons, may reflect continually altered afferent activity. Our findings support the view that long-term rearrangement of cortical representational maps is significantly determined within the thalamus.