Ventral Posterior Thalamic Nucleus Research Articles

Expression of Frizzled10 in mouse central nervous system

Frizzled transmembrane proteins (Fzd) are receptors of Wnts, and they play key roles during central nervous system (CNS) development in vertebrates. Here we report the expression pattern of Frizzled10 in mouse CNS from embryonic stages to adulthood. Frizzled10 is expressed strongly at embryonic days E8.5 and E9.5 in the neural tube and tail bud. At E10.5, Frizzled10 is expressed in the forebrain vesicle, the fourth ventricle and the dorsal spinal cord. From E12.5 to E16.5, Frizzled10 expression is mainly observed in the cortical hem/fimbria, the neuroepithelium of the third ventricular zone, midbrain, developing cerebellum, and dorsal spinal cord. At P0, with the exception of expression in the fimbria, Frizzled10 mRNA expression is limited to specific nuclei including the ventral posterior thalamic nucleus (VP) and the dorsal lateral geniculate nucleus (DLG) in the developing thalamus as well as in the proliferative ventricular zone of the developing cerebellum. From P20 to adult, Frizzled10 mRNA is detected only in the internal capsule (ic). Our data show that expression of Frizzled10 is very strong during embryonic development of the CNS and suggest that Frizzled10 may play an essential role in spatial and temporal regulation during neural development.

Spinocerebellar Ataxia Type 3 (SCA3): Thalamic Neurodegeneration Occurs Independently from Thalamic Ataxin‐3 Immunopositive Neuronal Intranuclear Inclusions

In the last years progress has been made regarding the involvement of the thalamus during the course of the currently known polyglutamine diseases. Although recent studies have shown that the thalamus consistently undergoes neurodegeneration in Huntington's disease (HD) and spinocerebellar ataxia type 2 (SCA2) it is still unclear whether it is also a consistent target of the pathological process of spinocerebellar ataxia type 3 (SCA3). Accordingly we studied the thalamic pathoanatomy and distribution pattern of ataxin-3 immunopositive neuronal intranuclear inclusions (NI) in nine clinically diagnosed and genetically confirmed SCA3 patients and carried out a detailed statistical analysis of our findings. During our pathoanatomical study we disclosed (i) a consistent degeneration of the ventral anterior, ventral lateral and reticular thalamic nuclei; (ii) a degeneration of the ventral posterior lateral nucleus and inferior and lateral subnuclei of the pulvinar in the majority of these SCA3 patients; and (iii) a degeneration of the ventral posterior medial and lateral posterior thalamic nuclei, the lateral geniculate body and some of the limbic thalamic nuclei in some of them. Upon immunocytochemical analysis we detected NI in all of the thalamic nuclei of all of our SCA3 patients. According to our statistical analysis (i) thalamic neurodegeneration and the occurrence of ataxin-3 immunopositive thalamic NI was not associated with the individual length of the CAG-repeats in the mutated SCA3 allele, the patients age at disease onset and the duration of SCA3 and (ii) thalamic neurodegeneration was not correlated with the occurrence of ataxin-3 immunopositive thalamic NI. This lack of correlation may suggest that ataxin-3 immunopositive NI are not immediately decisive for the fate of affected nerve cells but rather represent unspecific and pathognomonic morphological markers of SCA3.

Layer IV of the primary somatosensory cortex has the highest complexity under anesthesia and cortical complexity is modulated by specific thalamic inputs

The system complexity, as calculated from correlation dimension, embedded in each layer and its modulation by specific inputs and general excitatory state are not yet known. The aims of present study were to estimate the system complexity across the cortical layers by analyzing intracortical EEG signals using a nonlinear analytical method, and to identify how layer-related complexity varies with the alteration of thalamic input and brain state. Male Sprague–Dawley rats were anesthetized under l% halothane. Sixteen channels of evoked or spontaneous EEG signals were recorded simultaneously across the six cortical layers in the somatosensory cortex with a single Michigan probe. The system complexity was assessed by computing correlation dimension, D 2, based on the Nonlinear Time Series Analysis data analysis program. Cortical layer IV exhibited a D 2 value, 3.24, that was significantly higher than that of the other cortical layers. The D 2 values in layers IV and II/III were significantly reduced after reversible deactivation of the ventral posterior lateral thalamic nucleus. D 2 decreased with increases in administered halothane concentration from 0.75% to 2.0%, particularly in layer IV. The present findings suggest that cortical layer IV maintains a higher complexity than the other layers and that the complexity of the mid-cortical layers is subject to regulation from specific thalamic inputs and more sensitive to changes in the general state of brain excitation.

Traumatic axonal injury in the perisomatic domain triggers ultrarapid secondary axotomy and Wallerian degeneration

Traumatic axonal injury (TAI) arising from diffuse brain injury (DBI) results in focally impaired axonal transport with progressive swelling and delayed disconnection over several hours within brainstem axons. Neocortical DBI-mediated perisomatic axotomy does not result in neuronal death, suggesting that a comparably delayed axotomy progression was responsible for this unanticipated response. To evaluate delayed perisomatic axotomy, the current study was initiated. Rats received intracerebroventricular 10-kDa dextran followed by moderate midline/central fluid percussion injury (FPI) or FPI alone. At 15, 30, 60, and 180 min post-injury, light and transmission electron microscopy identified impaired axonal transport via antibodies targeting amyloid precursor protein (APP), while double-label fluorescent microscopy explored concomitant focal axolemmal alterations via dextran-APP co-localization. At 15 min post-injury, perisomatic TAI was identified with LM within dorsolateral and ventral posterior thalamic nuclei. Using TEM, many sustaining somata and related proximal/distal axonal segments revealed normal ultrastructural detail that was continuous with focal axonal swellings characterized by cytoskeletal and organelle pathology. In other cases, axotomy was confirmed by loss of axonal continuity distal to the swelling. By 30 min post-injury, perisomatic axotomy predominated. By 60–180 min, somatic, proximal axonal segment, and swelling ultrastructure were comparable to earlier time points although swelling diameter increased. Distal axonal segment ultrastructure now revealed the initial stages of Wallerian degeneration. The site of perisomatic axotomy did not internalize dextran, suggesting that its pathogenesis occurred independent of altered axolemmal permeability. Collectively, this DBI-mediated ultrarapid perisomatic axotomy and its sequelae further illustrate the varied axonal responses to trauma.

Responses of neurons in the rat ventral posterior lateral thalamic nucleus to noxious visceral and cutaneous stimuli

Visceral nociceptive responses to distention of the ureter, and responses to innocuous and noxious mechanical stimulation of the skin were recorded from neurons in the ventral posterior lateral nucleus of the thalamus in anesthetized rats. The ventral posterior lateral (VPL) neurons were classified by their responses to cutaneous stimuli as either low-threshold or wide-dynamic-range neurons. No high-threshold neurons were found in the population of VPL neurons sampled. Some VPL neurons that responded to distention of the ureter appeared to lack a cutaneous receptive field. The majority of VPL neurons that responded to noxious visceral stimulation of the ureter were classified as low-threshold neurons, based on their responses to cutaneous stimuli. Transection of the DC at an upper cervical level dramatically reduced the responses of VPL neurons to ureter distention and to innocuous mechanical stimulation of the skin, but the responses to noxious mechanical stimulation of the skin remained intact. Ureter distention and mechanical stimulation of the skin might activate dorsal horn neurons, including postsynaptic dorsal-column pathway (PSDC) neurons and spinothalamic tract (STT) cells. We conclude that both the DC pathway and the STT are likely to contribute to the visceral and somatic responses of some VPL neurons.

Extended pathoanatomical studies point to a consistent affection of the thalamus in spinocerebellar ataxia type 2

The involvement of the thalamus during the course of the currently known polyglutamine diseases is still a matter of debate. While it is well-known that this diencephalic nuclear complex undergoes neurodegeneration in some polyglutamine diseases such as Huntington's disease (HD), it has remained unclear whether and to what extent the thalamus is also involved in spinocerebellar ataxia type 2 (SCA2) patients. Encouraged by our recent post-mortem findings in one German SCA2 patient and the results of a recent nuclear magnetic resonance (NMR) study, we extended our pathoanatomical analysis to serial thick sections stained for lipofuscin granules and Nissl substance through the thalami of four additional German and Cuban SCA2 patients. According to this analysis the thalamus is consistently affected by the destructive process of SCA2. In particular, during our study we observed a consistent involvement of the lateral geniculate body, the lateral posterior, ventral anterior, ventral lateral, ventral posterior lateral, and ventral posterior medial thalamic nuclei as well as the extraterritorial reticular nucleus. In four of the SCA2 cases studied additional damage was seen in the inferior and lateral nuclei of the pulvinar, whereas in the minority of the patients a subset of the limbic nuclei of the thalamus (i.e. anterodorsal, anteroprincipal, laterodorsal, fasciculosus, mediodorsal, central lateral, central medial, cucullar, and paracentral nuclei, medial nucleus of the pulvinar) underwent neurodegeneration. These interindividual differences in the distribution pattern of thalamic neurodegeneration indicate that the thalamic nuclei differ in their proclivities to degenerate in SCA2 and may suggest that they become involved at different phases in the evolution of the underlying degenerative process.

The differential distribution of the growth-associated protein-43 in first and higher order thalamic nuclei of the adult rat

Corticothalamic axons from layer 5 of primary and secondary auditory and visual areas have large terminals that make multiple synaptic contacts on proximal dendrites of relay cells in higher order thalamic nuclei and have been termed “driver” inputs. The corticothalamic cells express mRNA for the presynaptic growth-associated protein-43, in the adult rat [Feig SL (2004) Corticothalamic cells in layers 5 and 6 of primary and secondary sensory cortex express GAP-43 mRNA in the adult rat. J Comp Neurol 468:96–111]. In contrast, ascending driver afferents to first order nuclei (e.g. retinal, inferior collicular, and lemniscal) lose growth-associated protein-43 as mature synaptic terminals are established. Levels of immunoreactivity for growth-associated protein-43 are compared for first and higher order visual (lateral geniculate and lateral posterior), auditory (ventral and dorsal divisions of the medial geniculate), and somatosensory (ventral posterior and posterior) thalamic nuclei. At one week postnatal, staining for growth-associated protein-43 is uniform throughout first and higher order thalamic nuclei. By three weeks and thereafter, staining is denser in the higher order than first order thalamic nuclei. Electron microscopy shows growth-associated protein-43 in profiles with characteristics of afferents from layer 5 in LP and medial geniculate nucleus and no such label in retinal afferents in lateral geniculate nucleus. In these nuclei, approximately 25% of the profiles with characteristics of cortical afferents from layer 6 have label for growth-associated protein-43. The superficial layers of the superior colliculus also show growth-associated protein-43 positive profiles with characteristics of terminals from cortical layer 5. Some growth-associated protein-43 positive terminals were also positive for GABA in the thalamic nuclei studied and in the superior colliculus. The data suggest that sensory afferents to first order thalamocortical relays become stabilized once mature synaptic patterns are established, but the higher stages of information processing involving higher order thalamic relays, via cells in cortical layer 5, retain plasticity related to growth-associated protein-43 in the adult.

Differential responses in three thalamic nuclei in moderately disabled, severely disabled and vegetative patients after blunt head injury.

In vivo imaging techniques have indicated for many years that there is loss of white matter after human traumatic brain injury (TBI) and that the loss is inversely related to cognitive outcome. However, correlated, quantitative evidence for loss of neurons from either the cerebral cortex or the diencephalon is largely lacking. There is some evidence in models of TBI that neuronal loss occurs within the thalamus, but no systematic studies of such loss have been undertaken in the thalamus of humans after blunt head injury. We have undertaken a stereological analysis of changes in numbers of neurons within the dorsomedial, ventral posterior and lateral posterior thalamic nuclei in patients assessed by the Glasgow Outcome Scale as moderately disabled (n = 9), severely disabled (n = 12) and vegetative (n = 10) head-injured patients who survived between 6 h and 3 years, and controls (n = 9). In histological sections at the level of the lateral geniculate body, the cross-sectional area of each nucleus and the number and the mean size of neurons within each nucleus was quantified. A statistically significant loss of cross-sectional area and number of neurons occurred in the dorsomedial nucleus in moderately disabled, and both the dorsomedial and ventral posterior thalamic nuclei in severely disabled and vegetative head-injured patients. However, there was no change in neuronal cell size. In the lateral posterior nucleus, despite a reduction in mean cell size, there was not a significant change in either nuclear area or number of neurons in cases of moderately disabled, severely disabled or vegetative patients. We posit, although detailed neuropsychological outcome for the patients included within this study was not available, that neuronal loss in the dorsomedial thalamus in moderately and severely disabled and vegetative patients may be the structural basis for the clinical assessment in the Glasgow Outcome Scale. In severely disabled and vegetative patients, loss of neurons from the ventral posterior thalamic nucleus may also reflect loss of response to afferent stimuli.

Organization of diencephalic projections from the spinal trigeminal nucleus oralis: An anterograde tracing study in the rat

The organization of the efferent projections from the spinal trigeminal nucleus oralis (Sp5O) to the diencephalon was studied in the rat using the anterograde tracer Phaseolus vulgaris leucoagglutinin. The present study confirms the existence of trigemino-thalamic pathways originating from the Sp5O and details their distribution. The main diencephalic targets of the Sp5O are the ventral posteromedial thalamic nucleus (VPM), the posterior thalamic nuclei (Po) and the ventral part of the zona incerta (ZIv), contralaterally, and the parvicellular part of the ventral posterior thalamic nucleus (VPpc), bilaterally. The distribution of these projections varies according to the dorso-ventral location of the injection sites: the dorsal part of the Sp5O projects to the medial part of the VPM and the Po, and to the caudal part of the ZIv, as well as to the VPpc. The ventral part of the Sp5O projects to the lateral part of the VPM and the Po and to the rostral part of the ZIv. These results suggest that the trigemino-diencephalic pathways originating from the Sp5O are involved in the processing of gustatory and somatosensory information.

A critical review of the role of the proposed VMpo nucleus in pain

The evidence presented by Craig and his colleagues for an important projection from lamina I spinothalamic tract neurons to a renamed thalamic nucleus (the posterior part of the ventral medial nucleus or VMpo), as well as to the ventrocaudal medial dorsal and the ventral posterior inferior thalamic nuclei, is critically reviewed. Of particular concern is the denial of an important nociceptive lamina I projection to the ventrobasal complex. Contrary evidence is reviewed that strongly favors a role of spinothalamic projections from both lamina I and deep layers of the dorsal horn to the ventrobasal complex and other thalamic nuclei and from there to the SI and SII somatosensory cortices in the sensory-discriminative processing of pain and temperature information. © 2002 by the American Pain Society

The ventral lateral posterior nucleus of the thalamus in schizophrenia: a post-mortem study

The ventral lateral posterior thalamic nucleus (VLp) is an integral part of both the cerebello-thalamocortical and the basal ganglia-thalamocortical circuit. Although both circuits are thought to be involved in the pathophysiology of schizophrenia, the VLp has not yet been examined in schizophrenia. Using stereological techniques in the brains of eight patients with schizophrenia and in eight age- and sex-matched controls, we measured the nuclear volume of the VLp and obtained estimates of the total number of neurons in this nucleus. Whole brain volume did not differ between the schizophrenia group and the control group and was not correlated to the volume of the right VLp or left VLp. The volume (−25%) and the total neuron number (−27%) of the left VLp were significantly reduced in the schizophrenia group. There were no significant differences in the nuclear volume, neuron density and total neuron number in the right VLp between the schizophrenia group and the control group. There were no significant correlations between length of illness and the nuclear volume, neuron density and total neuron number of the left and right VLp. The present results suggest that the total neuron number of the left VLp is reduced in the schizophrenia group, which may reflect disturbed cerebello-thalamocortical and basal ganglia-thalamocortical circuits in this disease.

Restricted expression of protocadherin 2A in the developing mouse brain

Protocadherins are cell–cell adhesion molecules that are thought to be involved in neural development. Here, we report the expression pattern of protocadherin 2A (Pc2A) in the developing mouse brain as determined by the in situ hybridization technique. In the postnatal day 2 brain, various regions expressed Pc2A including the cerebellar cortex, ventral posterior thalamic nucleus, dorsal lateral geniculate nucleus, hippocampus and cerebellum (Purkinje cells). In particular, some ependymal cells that form the lining of the lateral ventricle and the third ventricle and floor plate cells lining the fourth ventricle showed prominent expression. In the adult brain, strong expression was restricted to the Purkinje cells. Expression in other areas of the adult brain was down-regulated to a faint level, and only a weak signal was detected in regions such as the retina, olfactory bulb, dentate gyrus of the hippocampus, and in some parts of the medial eminence. These observations suggest that Pc2A is expressed in various regions of the brain in a developmentally regulated manner.

Delineation of thalamic nuclei immunoreactive for calcium-binding proteins in and around the posterior pole of the ventral posterior complex

An atlas of serial sections stained alternately for one of the three calcium-binding proteins, calbindin, calretinin or parvalbumin, or for markers that demarcate borders of thalamic nuclei in and around the posterior pole of the ventral posterior thalamic nucleus of a macaque monkey is presented. The concentrated focal zone of calbindin-immunoreactive fiber ramifications considered by others to form a specific pain and temperature relay nucleus is shown to be located entirely within the confines of the ventral posterior medial (VPM) nucleus. It contains a large population of calbindin-immunoreactive cells and overlaps a region of dense cell and fiber immunoreactivity for parvalbumin. In other parts of the ventral posterior complex, calbindin and parvalbumin immunoreactivity is complementary rather than co-extensive. It is unlikely that the zone of intense calbindin immunoreactivity in VPM forms the only thalamic relay for noxious thermal and mechanical inputs to the cerebral cortex.

Delineation of thalamic nuclei immunoreactive for calcium-binding proteins in and around the posterior pole of the ventral posterior complex

An atlas of serial sections stained alternately for one of the three calcium-binding proteins, calbindin, calretinin or parvalbumin, or for markers that demarcate borders of thalamic nuclei in and around the posterior pole of the ventral posterior thalamic nucleus of a macaque monkey is presented. The concentrated focal zone of calbindin-immunoreactive fiber ramifications considered by others to form a specific pain and temperature relay nucleus is shown to be located entirely within the confines of the ventral posterior medial (VPM) nucleus. It contains a large population of calbindin-immunoreactive cells and overlaps a region of dense cell and fiber immunoreactivity for parvalbumin. In other parts of the ventral posterior complex, calbindin and parvalbumin immunoreactivity is complementary rather than co-extensive. It is unlikely that the zone of intense calbindin immunoreactivity in VPM forms the only thalamic relay for noxious thermal and mechanical inputs to the cerebral cortex.

Transient cheiro-oral syndrome due to a ruptured intracranial dermoid cyst

We present here a case of episodic, pure cheiro-oral syndrome caused by a ruptured intracranial dermoid cyst. Cranial magnetic resonance imaging (MRI) using the fat-suppression method revealed a fatty mass lesion in the subarachnoid space of the left parasellar region and multiple lipid droplets in the subarachnoid space over the left perisylvian area. Although no evidence for it pathogenesis was obtained, the patient's cheiro-oral syndrome could have resulted from a transient vasospasm around the left ventral posterior thalamic nucleus or postcentral gyrus.

Differential synaptic distribution of AMPA receptor subunits in the ventral posterior and reticular thalamic nuclei of the rat

Although the mechanisms by which the cerebral cortex controls its ascending input are still poorly understood, it is known that cortical control at the thalamic level is via direct glutamatergic projections to relay nuclei and to the reticular nucleus. Here we confirm previous light microscopic reports of a high expression of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit, GluR4, in reticular and ventral posterior thalamic nuclei of the rat, and moderate staining using an antibody recognizing both GluR2 and GluR3. In contrast only low levels of staining for GluR2, and barely detectable levels of GluR1 immunoreactivity were observed. After injections of biotinylated dextran, electron microscopy revealed that anterogradely-labeled cortical synapses in both thalamic nuclei were small with fewer mitochondria and more densely-packed vesicles than terminals likely to arise from intrinsic and ascending pathways. We performed post-embedding immunogold to provide quantitative data on the density of AMPA receptor subunits at morphologically-defined groups of synapses. We found that corticothalamic synapses in the reticular thalamic nucleus contain twice as much GluR2/3, and at least three times more GluR4 protein than do intrathalamic synapses. In the ventral posterior nucleus, corticothalamic synapses contain similar amounts of GluR2/3, but four times more GluR4 than do those from ascending afferents. Corticothalamic synapses in reticular nucleus contain slightly more GluR2/3, and three times more GluR4, than those in ventral posterior nucleus. We conclude that enrichment of GluR4 at morphologically-defined cortical synapses is a feature common to both thalamic nuclei, and those in the reticular nucleus express higher levels of AMPA receptors. The rapid kinetics of GluR4-rich AMPA receptors we suggest indicate that cortical descending control may be more temporally precise than previously recognized.

Progressive Transneuronal Changes in the Brainstem and Thalamus after Long-Term Dorsal Rhizotomies in Adult Macaque Monkeys

This study deals with a potential brainstem and thalamic substrate for the extensive reorganization of somatosensory cortical maps that occurs after chronic, large-scale loss of peripheral input. Transneuronal atrophy occurred in neurons of the dorsal column (DCN) and ventral posterior lateral thalamic (VPL) nuclei in monkeys subjected to cervical and upper thoracic dorsal rhizotomies for 13-21 years and that had shown extensive representational plasticity in somatosensory cortex and thalamus in other experiments. Volumes of DCN and VPL, number and sizes of neurons, and neuronal packing density were measured by unbiased stereological techniques. When compared with the opposite, unaffected, side, the ipsilateral cuneate nucleus (CN), external cuneate nucleus (ECN), and contralateral VPL showed reductions in volume: 44-51% in CN, 37-48% in ECN, and 32-38% in VPL. In the affected nuclei, neurons were progressively shrunken with increasing survival time, and their packing density increased, but there was relatively little loss of neurons (10-16%). There was evidence for loss of axons of atrophic CN cells in the medial lemniscus and in the thalamus, with accompanying severe disorganization of the parts of the ventral posterior nuclei representing the normally innervated face and the deafferented upper limb. Secondary transneuronal atrophy in VPL, associated with retraction of axons of CN neurons undergoing primary transneuronal atrophy, is likely to be associated with similar withdrawal of axons from the cerebral cortex and should be a powerful influence on reorganization of somatotopic maps in the somatosensory cortex.

Changes in neuronal activities in the two ventral posterior medial thalamic nuclei in an experimental model of trigeminal pain in the rat by constriction of one infraorbital nerve

The present study analyzes the activity of 120 neurons recorded in the two ventro-postero-medial (VPM) nuclei of the thalamus in a rat model of trigeminal neuropathic pain. Twenty-eight rats were tested 2 weeks after a chronic constriction injury (CCI) of the infraorbital nerve (IoN). These animals exhibited violent pain-related reactions to extremely weak mechanical stimuli applied to the lesioned and, to a lesser extent, unlesioned IoN territories. The activities of neurons recorded in the VPMc ( n = 80) and VPMi ( n = 40), contralateral and ipsilateral to the injured nerve, respectively, were compared with those of 62 neurons recorded in the VPM of ten normal rats (VPMn). The neuronal background activity was higher in the VPM of CCI-IoN rats than in normal rats (about 4 vs 1 spike/s). The proportion of neurons which were driven by mechanical stimulations applied contralaterally to their recording site, was comparable in the three VPM (63-70%), but the effective stimulus modality differed significantly between the normal and the lesioned rats. In particular, the number of neurons driven by vibrissa or guard hair movements dramatically decreased in the VPM of CCI-IoN rats, mainly in the VPMc (67% of neurons with a receptive field (RF) in the VPMn vs 12% in the VPMc). Inversely, a consistent number of neurons in both the VPMc and VPMi were driven by other stimulus modalities applied to the IoN territory (moderate pressure for VPMc neurons, pinch or pinprick for both VPMc and VPMi neurons). The responses so induced were especially intense and included afterdischarges. In contrast to the VPMn neurons, the RFs of both the VPMc and VPMi neurons included two vibrissae at least, and were occasionally discontinuous and multimodal, including both vibrissae and cutaneous areas for VPMc units. The bilateral changes in VPM responsiveness and in behavior suggest the involvement of central processing of sensory information, which are set off by the CCI-IoN. The putative mechanisms and functional implication of the changes in the VPM neuronal activities are discussed.

Low-voltage-activated calcium channel subunit expression in a genetic model of absence epilepsy in the rat

The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are an inbred strain of rats that display many of the characteristics of human absence epilepsy. In these rats, reciprocal thalamocortical projections play a critical role in the generation of spike-and-wave discharges that characterize absence seizures. When compared to those of the non-epileptic control strain, juvenile animals of the GAERS strain reportedly possess higher-amplitude T-type calcium currents in neurons of the thalamic reticular nucleus (nRt). We hypothesized that differences in calcium currents seen between GAERS and controls result from differences in expression of genes for low-voltage-activated calcium channels. Quantitative in situ hybridization was used to compare expression of α1G, α1H, α1I, and α1E calcium channel subunit mRNAs from adult and juvenile animals of the two strains. We found higher levels of α1H mRNA expression in nRt neurons of juvenile animals (34.9±2.3 vs. 28.4±1.8 grains/10 3 pixels, p<0.05), perhaps accounting in part for earlier reports of elevated T-type current amplitude in those cells. In adult GAERS animals, we found elevated levels of α1G mRNA in neurons of the ventral posterior thalamic relay nuclei (64.8±3.5 vs. 53.5±1.7 grains/10 3 pixels, p<0.05), as well as higher levels of α1H mRNA in nRt neurons (32.6±0.8 vs. 28.2±1.6 grains/10 3 pixels, p<0.05). These results suggest that the epileptic phenotype apparent in adult GAERS may result in part from these significant, albeit small (∼15–25%), elevations in T-type calcium channel mRNA levels.

Parabrachial nucleus projections to midline and intralaminar thalamic nuclei of the rat.

The projections from the parabrachial nucleus to the midline and intralaminar thalamic nuclei were examined in the rat. Stereotaxic injections of the retrograde tracer cholera toxin-beta (CTb) were made in each of the intralaminar nuclei of the dorsal thalamus (the lateral parafascicular, medial parafascicular, oval paracentral, central lateral, paracentral, and central medial nuclei), as well as the midline thalamic nuclei (the paraventricular, intermediodorsal, mediodorsal, paratenial, rhomboid, reuniens, parvicellular part of the ventral posterior, and caudal ventral medial nuclei). The retrograde cell body labeling pattern within the parabrachial subnuclei was then analyzed. The paracentral thalamic nucleus received an input only from the internal lateral parabrachial subnucleus. However, this subnucleus also projected to all the other intralaminar thalamic nuclei, except for the central lateral thalamic nucleus, which received no parabrachial afferent inputs. The external lateral parabrachial subnucleus projected to the lateral parafascicular, reuniens, central medial, parvicellular part of the ventral posterior, and caudal ventromedial thalamic nuclei. Following CTb injections in the paraventricular thalamic nucleus, retrogradely labeled cells were found in the central lateral, dorsal lateral, and external lateral parabrachial subnuclei. The medial and ventral lateral parabrachial subnuclei projected to the oval paracentral, parafascicular, and rhomboid thalamic nuclei. Finally, the waist area of the parabrachial nucleus was densely labeled after CTb injections in the parvicellular part of the ventral posterior thalamic nucleus. Nociceptive, visceral, and gustatory signals may reach specific cortical and other forebrain sites via this parabrachial-thalamic pathway.