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PubMed1997

Collateral projections from single neurons in the dorsal column nucleus to both the cochlear nucleus and the ventrobasal thalamus: a retrograde double-labeling study in the rat.

In the rats which were injected with Fluoro-Gold into the cochlear nucleus and simultaneously with tetramethylrhodamine-dextran amine into the ventrobasal thalamus, a number of neurons in the gracile and the cuneate nuclei of the dorsal column nucleus (DCN) and in the interpolar and caudal subnuclei of the spinal trigeminal nucleus (STN) were double-labeled retrogradely with the both tracers. The results indicated the existence of single DCN/STN-neurons which provided axons to the cochlear nucleus, mainly ipsilaterally, and to the contralateral ventrobasal thalamus.

Animals↗
PubMed2000

Modulation of nociceptive transmission by NMDA/glycine site receptor in the ventroposterolateral nucleus of the thalamus.

NMDA-type glutamate receptors are involved in the generation and maintenance of altered pain states. In the present study, we examined the effect of an NMDA-glycine site antagonist, GV196771A [E-4, 6-dichloro-3-(2-oxo-1-phenyl-pyrrolidin-3-ylidenemethyl)-1H- indole-2- carboxylic acid sodium salt], on responses to noxious stimuli both in normal rats and during peripheral mononeuropathy induced by chronic constriction injury (CCI) of the sciatic nerve. In one series of experiments, activity of nociceptive neurons in the ventroposterolateral (VPL) nucleus of the thalamus was recorded in response to pressure stimuli to the contralateral hindpaw. Intravenous injection (iv) of the glycine antagonist had no effect on these cells in normal rats. When tested in rats with CCI induced 2-3 weeks previously, however, GV196771A (0.125, 0.5 and 2.0mg/kg) blocked responses to noxious stimulation in a dose-dependent and reversible manner. Morphine (0.5mg/kg, iv) and the NMDA channel blocker MK801 (0.1mg/kg, iv) suppressed noxious stimulus-evoked activity of VPL neurons in both normal and CCI-treated rats. MK801 also decreased the responses of non-nociceptive neurons to brush stimulation in both sets of animals, in contrast to the glycine antagonist which did not alter the responses of these cells. Similar results were obtained from a series of behavior experiments in which the latency for paw withdrawal from heat stimulation was measured in normal and CCI-treated rats. GV196771A (3 and 10mg/kg) injected orally, reduced the hyperalgesic response in the treated rats but did not change the withdrawal latency in normal rats. Taken together, these findings suggest that block of the NMDA receptor decreases nociceptive transmission in the thalamus and can modulate hyperalgesic states. GV196771A and glycine antagonists in general may represent innovative and safe agents for the treatment of neuropathic pain.

Analgesics, Opioid↗
PubMed1998

GABAergic and cholinergic basal forebrain and preoptic-anterior hypothalamic projections to the mediodorsal nucleus of the thalamus in the cat.

The present study examined projections of GABAergic and cholinergic neurons from the basal forebrain and preoptic-anterior hypothalamus to the "intermediate" part of the mediodorsal nucleus of the thalamus. Retrograde transport from this region of the mediodorsal nucleus was investigated using horseradish peroxidase-conjugated wheatgerm agglutinin in combination with peroxidase-antiperoxidase immunohistochemical staining for glutamic acid decarboxylase and choline acetyltransferase. A relatively large number of retrogradely-labelled glutamic acid decarboxylase-positive neurons are located in the basal forebrain, amounting to more than 7% of the total population of glutamic acid decarboxylase-positive cells in this region. Moreover, retrogradely-labelled choline acetyltransferase-positive cells are interspersed among glutamic acid decarboxylase-positive neurons, accounting for about 6% of the total choline acetyltransferase-positive cell population in the basal forebrain. The glutamic acid decarboxylase-positive and choline acetyltransferase-positive retrogradely-labelled neurons are distributed throughout several regions of the basal forebrain, including the medial septum, the diagonal band of Broca, the magnocellular preoptic nucleus, the substantia innominata pars anterior, the substantia innominata pars posterior, and the globus pallidus where only a few retrogradely-labelled neurons were seen. The choline acetyltransferase-positive mediodorsal-projecting neurons are morphologically different from the choline acetyltransferase-positive neurons in the basal forebrain, suggesting that those projecting to the mediodorsal nucleus are a small proportion of the cholinergic neuronal population in the basal forebrain. In the preoptic-anterior hypothalamus, many retrogradely-labelled glutamic acid decarboxylase-positive cells were found, amounting to more than 7% of the total population of glutamic acid decarboxylase-positive cells in this region. These retrogradely-labelled glutamic acid decarboxylase-positive neurons are distributed throughout the preoptic-anterior hypothalamus in a continuous line with those in the basal forebrain, including the lateral preoptic area, the medial preoptic area, the bed nucleus of the stria terminalis, and the anterior and dorsal hypothalamic areas. The highest percentage of mediodorsal-projecting GABAergic neurons is in the anterior lateral hypothalamus where more than 25% of the total population of glutamic acid decarboxylase-positive cells project to the mediodorsal nucleus of the thalamus. Overall, of the large population of retrogradely-labelled neurons in the basal forebrain and preoptic-anterior hypothalamus, a significant proportion are glutamic acid decarboxylase-positive neurons (> 60% in the basal forebrain and > 30% in the preoptic-anterior hypothalamus), while the choline acetyltransferase-positive neurons amount to a smaller percentage of the neurons projecting to the mediodorsal nucleus (< 13% in the basal forebrain and < 2% in the preoptic-anterior hypothalamus). These results provide anatomical evidence of direct GABAergic projections from the basal forebrain and preoptic-anterior hypothalamic regions to the "intermediate" part of the mediodorsal nucleus in the cat. This GABAergic projection field could be the direct pathway by which the basal forebrain directly modulates thalamic excitability and may also be involved in mechanisms modulating electroencephalographic synchronization and sleep through the "intermediate" mediodorsal nucleus.

Animals↗
PubMed2002

Descending projections to the inferior colliculus from the posterior thalamus and the auditory cortex in rat, cat, and monkey.

Projections from the posterior thalamus and medial geniculate body were labeled retrogradely with wheat germ agglutinin conjugated to horseradish peroxidase injected into the rat, cat, and squirrel monkey inferior colliculus. Neurons were found ipsilaterally in the (1) medial division of the medial geniculate body, (2) central gray, (3) posterior limitans nucleus, and the (4) reticular part of the substantia nigra. Bilateral projections involved the (5) peripeduncular/suprapeduncular nucleus, (6) subparafascicular and posterior intralaminar nuclei, (7) nucleus of the brachium of the inferior colliculus, (8) lateral tegmental/lateral mesencephalic areas, and (9) deep layers of the superior colliculus. The medial geniculate projection was concentrated in the caudal one-third of the thalamus; in contrast, the labeling in the subparafascicular nucleus, substantia nigra, and central gray continued much further rostrally. Robust anterograde labeling corresponded to known patterns of tectothalamic projection. Biotinylated dextran amine deposits in the rat inferior colliculus revealed that (1) many thalamotectal cells were elongated multipolar neurons with long, sparsely branched dendrites, resembling neurons in the posterior intralaminar system, and that other labeled cells were more typical of thalamic relay neurons; (2) some cells have reciprocal projections. Similar results were seen in the cat and squirrel monkey. The widespread origins of descending thalamic influences on the inferior colliculus may represent a phylogenetically ancient feedback system onto the acoustic tectum, one that predates the corticocollicular system and modulates nonauditory centers and brainstem autonomic nuclei. Besides their role in normal hearing such pathways may influence behaviors ranging from the startle reflex to the genesis of sound-induced seizures.

Animals↗
PubMed2001

Progressive neuronal loss in the ventral posterior lateral and medial nuclei of thalamus in Niemann-Pick disease type C mouse brain.

Niemann-Pick disease type C (NP-C) disease is a progressive and fatal neurological disorder characterized by accumulation of cholesterol and glycosphingolipids in peripheral tissues and that of glycosphingolipids in the brain. A C57BL/KsJ-npc1(spm) mutant strain is a genetically authentic model of NP-C. This study investigated neuronal cell loss and lipid accumulation in the npc1(spm) mouse brain. Nissl-staining revealed abundant swollen neurons in the neocortex, piriform cortex, hippocampus and basal ganglia at 3-4 wk of age. In addition to loss of the Purkinje cells, we found a conspicuous cell loss in the ventral posterial lateral (VPL) and medial (VPM) nuclei of thalamus, which became apparent after 4-5 wk. Biochemical analyses revealed no increase of cholesterol in the lipid extracts whereas a substantial accumulation of cholesterol was detectable in most of the large neurons by filipin staining in the brain of homozygous mice. In contrast to the diffuse staining pattern in normal brains, the neuropils of the neurons in the brain of homozygous mice were stained in a punctate pattern. The ubiquitous accumulation excludes a direct role of cholesterol in the progressive neuronal loss in the Purkinje cell layer and in the VPL and VPM of the thalamus.

Aging↗
PubMed2001

Development of the evoked potentials in the thalamus and cerebral cortex after stimulation of the stellate ganglion afferents in kittens.

The primary evoked potentials (EP) were studied in newborn, 10-, 20-day-old, 1-month-old kittens in the thalamus and cerebral cortex after stimulation of the stellate ganglion (SG) afferents. The nerves were irritated with single square-wave pulses with an amplitude of 1.2-1.3 threshold for EP appearance. In all kittens, EP were registered in the same zones as in adult animals. In the thalamus, this zone was represented by the centromedial part of the ventralis posterior lateralis (n. VPL), contralaterally to the stimulation place. In the cerebral cortex, the EP were observed in the cerebral cortex, specifically in the somatosensory zones S1 and S2 also contralaterally to the stimulation place. In postnatal ontogenesis, the latency of evoked potentials decreases, amplitude increases and the form of these potentials transforms from negative in newborn kittens to positive-negative wave in 1-month-old animals. Maturation of the SG afferent pathways exists in parallel with the somatosensory ones and does not finish at 1 month of life.

Afferent Pathways↗
PubMed1980

Early and late acquisition of discriminative neuronal activity during differential conditioning in rabbits: specificity within the laminae of cingulate cortex and the anteroventral thalamus.

Multiple-unit activity of the cingulate cortex and the anteroventral (AV) nucleus of the thalamus was recorded during discriminative conditioning of an avoidance response (locomotion) in rabbits. The results indicated a greater unit response in cingulate cortex to the positive conditional stimulus (CS+; a tone paired with a footshock unconditional stimulus [UCS]) relative to the negative conditional stimulus (CS-; a tone randomly interspersed with the positive stimuli but never paired with the UCS). The majority of neuronal records obtained from the deep laminae (V and VI) of cingulate cortex manifested first neuronal discrimination in the session of first exposure to conditioning. However, the majority of neuronal records of the superficial laminae (I-IV) showed first discrimination at a late stage of training, during the session in which the criterion of behavioral discrimination was met. The late developing discriminative activity of the superficial laminae was coincident with the late developing discriminative activity of the AV thalamus. Once acquired, neuronal discrimination in cortex persisted throughout 600 msec after CS onset, and during six sessions of training (overtraining) beyond criterion. Analysis of individual neuronal records suggested that the persistence during overtraining resulted from replacement of early fading neuronal discriminations by late neuronal discriminations.

Animals↗
PubMed1998

A new intrathalamic pathway linking modality-related nuclei in the dorsal thalamus.

Transmission of sensory information through the dorsal thalamus involves two types of modality-related nuclei, first order and higher order, between which there are thought to be no intrathalamic interactions. We now show that within the somatosensory thalamus, cells in one nucleus, the ventrobasal complex, can influence activity in another nucleus, the medial division of the posterior complex. Stimulation of ventrobasal complex cells evoked inhibitory postsynaptic currents in cells of the medial division of the posterior complex. These currents exhibited the reversal potential and pharmacology of a GABAA receptor-mediated chloride conductance, indicating that they result from the activation of a disynaptic pathway involving the GABAergic cells of the thalamic reticular nucleus. These findings provide the first direct evidence for intrathalamic interactions between dorsal thalamic nuclei.

Animals↗
PubMed2006

Functional alignment of feedback effects from visual cortex to thalamus.

Following from the classical work of Hubel and Wiesel, it has been recognized that the orientation and the on- and off-zones of receptive fields of layer 4 simple cells in the visual cortex are linked to the spatial alignment and properties of the cells in the visual thalamus that relay the retinal input. Here we present evidence showing that the orientation and the on- and off-zones of receptive fields of layer 6 simple cells in cat visual cortex that provide feedback to the thalamus are similarly linked to the alignment and properties of the receptive fields of the thalamic cells they contact. However, the pattern of influence linked to on- and off-zones is phase-reversed. This has important functional implications.

Action Potentials↗
PubMed2000

Bicuculline injections into the rostral and caudal motor thalamus of the monkey induce different types of dystonia.

The pathophysiology of dystonia remains unclear in comparison with other movement disorders. Recent data suggest that there may exist in dystonia an increased thalamic drive to the mesial premotor cortex. To test this hypothesis, we induced overactivity of the motor thalamus by injecting a GABA-A (gamma-aminobutyric acid) antagonist (bicuculline) into the rostral (pallidal) and caudal (cerebellar) ventrolateral nuclei of the thalamus in both hemispheres of one monkey. Dystonic postures were observed in the contralateral limbs and axis. Electromyographic recordings revealed bursts of muscular activation with co-contractions during spontaneous dystonic movements and alterations in muscular patterns during sequential visually guided arm movements. The type of dystonia depended on the site of injections. Rostral thalamic injections induced more severe dystonic postures, whereas myoclonic jerks predominated following caudal injections. We conclude that these two distinct clinical patterns, which are frequently associated in humans, are probably due to a dysfunctioning of segregated thalamic projections to the supplementary motor area (from the rostral part) and to the primary motor cortex (from the caudal part).

Animals↗
PubMed2000

Subnucleus-specific loss of neurons in medial thalamus of schizophrenics.

The hypoactivity of dorsolateral prefrontal cortex in schizophrenics is well known. One cause of this hypoactivity may be defective corticocortical or thalamocortical connections. Recent imaging studies of the thalamus suggest reductions in volume of the whole thalamus and reduced activity in the medial group of thalamic nuclei, which may indicate loss of functional input to the cortex. Using stereological techniques in six pairs of individually matched brains from schizophrenics and controls, we measured the volumes and obtained estimates of the number of neurons in the three subnuclei (parvocellular, pc; densocellular, dc; magnocellular, mc) of the mediodorsal nucleus (MD) and from the ventral posterior medial nucleus. There was a significant reduction in total neuron number in MD as a whole but this neuron loss was largely restricted to MDpc and MDdc [-30.9 and -24.5%, respectively (P </= 0.01)]. MDmc and the control ventral posterior medial nucleus showed no significant changes in cell number. Because the subnuclei of MD have different connections and project to different areas of the frontal cortex, the specific loss of neurons in MDpc and MDdc has implications for the functional defects observed in schizophrenia.

Adult↗
PubMed2000

Metabotropic transmitter actions in auditory thalamus.

Neurons in the ventral partition of the medial geniculate body (MGBv), the primary auditory thalamus, receive afferent input from the inferior colliculus via excitatory glutamate-ergic and inhibitory GABA-ergic input fibres. The feedback from the auditory cortex to the thalamic relay also is mediated via neuron systems using glutamate and GABA as transmitters. We studied effects on excitability mediated by these transmitters via G-protein coupled metabotropic receptors. In a slice preparation of rat thalamus we investigated the membrane responses of MGBv neurons using the whole cell recording technique. Application of a metabotropic glutamate receptor (mGluR) agonist, ACPD (5-100 microM), depolarized MGBv neurons. As a result, the burst mode of firing, which characterizes states of sleep at hyperpolarized potentials was replaced by the tonic mode, which is compatible with sound signal transmission during alertness. The depolarization was caused by an inward current (I(ACPD)) that persisted during blockade of Na+ channels with tetrodotoxin (TTX) and of Ca2+ channels with Cd2+. The I(ACPD) depended, however, on extracellular Na+, which could be replaced with Li+, excluding a major contribution of the Na+/Ca2+ exchange current. ACPD application also inhibited an inwardly rectifying K+ current at hyperpolarized potentials and activated an outward current in the depolarized range. Application of the GABA(B) agonist, baclofen (10 microM), hyperpolarized MGBv neurons by activation of an inwardly rectifying K+ current. The corresponding membrane conductance acted as a powerful shunt that reduced voltage responses and inhibited firing in both the tonic and burst modes. Thus, the effects of GABA(B) receptor activation would suppress auditory signal transfer, whereas mGluR activation enhances excitability, possibly accounting for the alerting effects of certain auditory stimuli.

Animals↗
PubMed2000

Attention-related, cross-modality modulation of somatosensory neurons in primate ventrobasal (VB) thalamus.

Attention-related modulation (AM) of the somatosensory responses of single neurons has been demonstrated in the cerebral cortex and medullary dorsal horn, but not in the ventrobasal thalamus. The somatically evoked activity was recorded of single units in the ventral posterior lateral thalamus (VPL) of awake monkeys while they detected the termination of task-relevant somatic or visual stimuli. Eighteen of 56 somatically responsive VPL neurons are reported that were recorded for enough time for a complete analysis of their responses during both the visual and somatic attention tasks. All neurons were spontaneously active and responded either to innocuous cutaneous (13/18) or deep (5/18) stimuli. Seven neurons (7/18, 38.8%) showed AM of somatosensory responsiveness. Two cells (2/7, 28.6%) showed AM only during the visual task, two others (2/7, 28.6%) only during the somatosensory task, and three cells (3/7, 42.8%) showed AM during both tasks. All five cells showing AM during the somatosensory task had enhanced responses to the task-relevant somatic stimulus. In contrast, the somatosensory responses of all five cells showing AM during the visual task were reduced. It is concluded that selective attention is associated with a modality specific modulation of the somatosensory responses of a sub-population of neurons within the primate VPL nucleus.

Animals↗
PubMed2007

Excess of neurons in the human newborn mediodorsal thalamus compared with that of the adult.

The aim of this study was to quantify the total number of neurons and glial cells in the mediodorsal nucleus of the thalamus (MD) of 8 newborn human brains, in comparison to 8 adult human brains. The estimates of the cell numbers were obtained using the stereological principles of the optical fractionator. In the case of the adults, the total number of neurons in the entire MD was an average of 41% lower than in the newborn, which was statistically highly significant (P < 0.001). The estimated average total number of neurons in MD thalamus of the newborns was 11.2 million (coefficient of variation [CV] = standard deviation/mean = 0.16), compared with the adults' 6.43 million (CV = 0.15). The glial cell numbers were substantially higher in the adult brains, with an increase of almost 4 times from 10.6 million at birth to 36.3 million in the fully developed adult brain. This is the first demonstration of a higher number of human neurons in the brain of newborns compared with the adult.

Adult↗
PubMed1991

Functional reorganization in adult monkey thalamus after peripheral nerve injury.

Large changes in somatotopic organization can be induced in adult primate somatosensory cortex by cutting peripheral afferents. The role, if any, of the thalamus in these changes has not been investigated previously. In the present experiments, electrophysiological recording in the ventroposterior lateral nucleus (VPL) has revealed that not only can reorganization occur in the thalamus, but it may be as extensive as that revealed in the cortex of the same monkeys. Thus, for at least some types of deafferentation, the reorganization revealed in the cortex may depend largely on subcortical changes.

Animals↗
PubMed1997

Reciprocal talk between the auditory thalamus and the hypothalamus: an antidromic study.

In this study we sought to validate physiologically the hypothalamus afferent projections from the auditory thalamus previously identified with tract tracing techniques in the ring dove. In total, we recorded the responses of 628 units in the nucleus ovoidalis (Ov) and its shell region to electrical stimulation applied to anterior hypothalamus and ventromedial nucleus. Ninety-six acoustic units in the shell region displayed good antidromic responses, confirming this region's axonal projections into these nuclei of the hypothalamus. Orthodromic responses (143 units) recorded in the Ov-Ov shell region suggest on the other hand reciprocal projections from the hypothalamus back to the auditory thalamus.

Afferent Pathways↗
PubMed1990

Paraneoplastic encephalomyelitis. An autopsy case with encephalitis principally confined to the thalamus and associated with pulmonary and gastric cancers.

We report an autopsy case of encephalitis principally confined to the bilateral thalamus and associated with pulmonary and gastric cancers. An 81-year-old man exhibiting behavioral abnormalities and progressive somnolence died of pneumonia 11 months after onset. Because the patient had lung cancer and no definite cause of the encephalitis was found, this case was categorized as one of paraneoplastic encephalomyelitis. This may be the first reported case of this condition in which the central nervous system (CNS) lesion was located predominantly in the thalamus.

Aged↗
PubMed1997

Suspected acute encephalopathy with symmetrical abnormal signal areas in the basal ganglia, thalamus, midbrain and pons diagnosed by magnetic resonance imaging.

A 4-year-old boy was admitted with disturbed consciousness following a convulsion. He developed bilateral pyramidal tract signs and showed a decerebrate posture. Laboratory findings revealed severe liver dysfunction and disseminated intravascular coagulation. On the eighth day eight in hospital he developed parkinsonism. However, 5 months from onset he had recovered almost completely. Brain CT on admission showed low density areas in the basal ganglia, thalamus, midbrain and pons. A T2-weighted scan in magnetic resonance imaging (MRI) showed almost symmetrical high signal intensities in both basal ganglia (including putamen, caudate nucleus, globus pallidus), external capsule, internal capsule thalamus, midbrain, pons and white matter of the peribasal ganglia; but a T1-weighted scan showed low signal intensities in the same regions during all phases. Therefore hemorrhagic lesions or the presence of thalamic methemoglobin were excluded. It was considered that the pathogenesis may be cytotoxic cellular edema due to cytotoxic agents or acute metabolic factors. Clinical presentation, laboratory findings and radiological findings were most suggestive of acute necrotizing encephalopathy. As differential diagnoses, acute disseminated encephalomyelitis and brainstem encephalitis were considered.

Acute Disease↗