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Preferential coassembly of alpha4 and delta subunits of the gamma-aminobutyric acidA receptor in rat thalamus.

Pharmacological study of rat thalamic gamma-aminobutyric acidA (GABAA) receptors revealed the presence of two distinct populations, namely, diazepam-sensitive and diazepam-insensitive [3H]Ro15-4513 binding sites accounting for 94 +/- 2% (1339 +/- 253 fmol/mg protein) and 6 +/- 2% (90 +/- 44 fmol/mg protein) of total sites, respectively. Thalamic diazepam-insensitive sites exhibited a pharmacology that was distinct from diazepam-sensitive sites but comparable to that of the alpha4beta3gamma2 subtype of the GABAA receptor stably expressed in L(tk-) cells. Immunoprecipitation experiments with a specific anti-alpha4-antiserum immunoprecipitated 20 and 7% of total thalamic [3H]muscimol and [3H]Ro15-4513 sites, respectively. Combinatorial immunoprecipitation using antisera against the alpha4, gamma2, and delta subunit revealed that alpha4delta- and alpha4gamma2-containing receptors account for 13 +/- 2 and 8 +/- 3% of [3H]muscimol sites from thalamus, respectively. It also indicated that all delta subunits coexist with an alpha4 subunit in this brain region. In conclusion, our results show that in rat thalamus both alpha4betagamma2 and alpha4betadelta subtypes are expressed but alpha4betadelta is the major alpha4-containing GABAA receptor population.

Affinity Labels↗

Sonographic finding of the bright thalamus.

Six of 83 asphyxiated neonates showed a diffuse increase of echodensity in bilateral thalami with or without other lesions in the basal ganglia on sonographic examination. The thalamic image still had a fairly high echogenecity compared with the surrounding brain parenchyma on follow up examination and was hence termed the bright thalamus. These six patients had a poor neurological outcome, including psychomotor retardation, spastic diplegia or quadriplegia, microcephaly, failure to thrive, seizures, and one death. The bright thalamus is not an occasional or an isolated sonographic finding of hypoxic-ischaemic encephalopathy, but it may serve as a landmark of severe hypoxic brain damage with adverse outcome.

Asphyxia Neonatorum↗

Movement disorders in astrocytomas of the basal ganglia and the thalamus.

In a series of 225 patients with astrocytomas (grades I-IV) of the basal ganglia and the thalamus, 20 had a movement disorder. In all patients the histological diagnosis was verified by stereotactic biopsy. Tremor was observed in twelve patients, dystonia in eight, chorea in three, and chorea/ballismus and myoclonus in one. The tumour involved the thalamus in 16 patients. Corticospinal tract dysfunction was evident in 70% of the patients with movement disorders and in 73% of those without. Demographic, clinical, histological and neuroradiological data of the patients with a movement disorder were compared with the data of patients without. CT data yielded no differences with respect to the involvement of anatomical structures. Movement disorders were significantly associated with low-grade astrocytomas.

Adolescent↗

Auditory saccade impairment after central thalamus lesions.

Visual and auditory saccades were studied in three patients with an isolated lesion located in the central thalamus. Visual saccades proved to be normal, whereas for auditory stimuli, the amplitude of the first saccade was asymmetric: saccades ipsilateral to the lesion were significantly smaller than those directed to the contralateral side. The patients were able to make a corrective saccade and hence to improve gain and to decrease gain asymmetry. It is suggested that patients were able to localise auditory targets correctly, but did not correctly take into account eye position during the saccade, probably as a consequence of an inaccurate efference copy (corollary discharge) signal. The findings are in keeping with the hypothesis that the central thalamus deals with saccades that are based on extraretinal signals.

Acoustic Stimulation↗

Increased ictal perfusion of the thalamus in paroxysmal kinesigenic dyskinesia.

The ictal and interictal cerebral blood flow (CBF) were evaluated in a patient with right unilateral short lasting paroxysmal kinesigenic dyskinesia, by means of single photon emission computed tomography (SPECT). The patient was a 6 year old boy with no family history. During an attack, increased CBF was seen in the left thalamus. Subtraction of interictal CBF from ictal CBF disclosed a prominent increase in CBF in the left posterolateral part of the thalamus. This finding suggests that abnormal hyperactivity of thalamic neurons could be responsible for the pathophysiology of paroxysmal kinesigenic dyskinesia in this patient.

Blood Flow Velocity↗

Neurotransmitters in the thalamus relaying visceral input to the insular cortex in the rat.

Neurotransmitters relaying ascending visceral information were examined by comparing the response of neurons in the insular cortex to vagal stimulation (0.8 Hz, 2 mA) before and after neurotransmitter antagonist injections (200 nl) in the ventroposterior parvocellular nucleus of the thalamus (VPpc). Cobalt (10 mM; presynaptic blocker) and kynurenate (100 microM; nonspecific excitatory amino acid antagonist) injections in the VPpc resulted in an attenuation (73-100 and 38-98%, respectively) of the evoked cortical response. Injections of the specific N-methyl-D-aspartate (NMDA) antagonist DL-2-amino-5-phosphonopentanoic acid (200 microM and 2 mM) did not affect the vagally evoked response, whereas the nonspecific non-NMDA antagonist L-glutamic acid diethylester (200 microM) attenuated the vagally evoked response by 66-100%. Three concentrations of the DL-alpha-amino-3-hydroxy-5-methylisoxazole-propionic acid (AMPA)-specific antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 and 200 microM and 2 mM) attenuated the vagally evoked cortical response by 29 +/- 9, 31 +/- 10, and 59 +/- 8%, respectively. The more selective AMPA antagonist 6-nitro-7-sulphamoylbenzo(f)quinoxaline-2,3-dione (200 microM and 2 mM) inhibited the vagally evoked cortical response by 53 +/- 8 and 52 +/- 3%, respectively. Phentolamine (0.1 and 1.0 microM), a general alpha-adrenergic antagonist, and picrotoxin (0.1 and 1.0 microM), a GABA(A) antagonist, did not affect the vagally evoked response. Atropine, a muscarinic cholinergic antagonist, decreased the vagally evoked response by 40 +/- 2% at a concentration of 0.1 microM, but a higher concentration of 1.0 microM had no effect. These results indicate that the non-NMDA excitatory amino acid receptor is necessary for the relay of visceral information in the VPpc. Muscarinic receptors may modulate visceral neuronal excitability in the VPpc, although the exact interaction between the inhibitory (m2) and excitatory (m3 or m5) muscarinic receptor types found in the thalamus is not known.

2-Amino-5-phosphonovalerate↗

OFF responses in the auditory thalamus of the guinea pig.

ON and OFF auditory responses were examined in the medial geniculate body (MGB) of the guinea pig. Single- and multiunit recordings were carried out on 12 anesthetized animals, and noise-burst or pure-tone stimuli were applied to the ear contralateral to the recording hemisphere. One hundred and thirty-five OFF or ON-OFF neurons and 160 ON neurons were studied, and the tuning curves of 21 ON-OFF or OFF neurons were examined from various nuclei of the MGB. The mean minimum threshold of the OFF responses (40.8 +/- 20.0 dB SPL, mean +/- SD; range: 0-80 dB SPL) was significantly higher than that of the ON responses (28.5 +/- 17.6 dB SPL, range: 0-60 dB SPL; n = 17, P < 0.001). Of 10 ON-OFF neurons that showed identifiable tuning frequencies for both ON and OFF responses, 7 showed a higher OFF than ON best frequency (BF), 2 showed the same BF for both ON and OFF, and only 1 showed a slightly lower OFF than ON BF. Most OFF responses sampled from the borders of the ventral (MGv) and the rostromedial (MGrm) nuclei of the MGB showed single-peaked tuning curves, similar to those of the ON responses in the MGv. The neurons located in the shell (MGs) and dorsal (MGd) nuclei of the MGB showed complicated-either multi-peaked or broad-tuning curves. All OFF responses showed long-duration-selectivity for acoustic stimuli: the mean half-maximum duration was 116.5 +/- 114.8 ms (n = 19, range: 27-411 ms). The latencies of 135 OFF responses were studied in various divisions of the MGB. The ventral border region of MGv showed the shortest latency, followed by the dorsal border region of the MGv, the MGrm, and the caudomedial nucleus (MGcm) of the MGB. The posterior nucleus of the thalamus (Po), the MGd, and the MGs showed much longer mean latencies of >30 ms (P < 0.05 compared with the border regions of the MGv, ANOVA), with Po showing the greatest mean latency of 60.3 ms and the greatest deviation of 25.5 ms). The latency of the OFF response (29.0 +/- 14.0 ms, n = 135) was significantly greater than that of the ON response (15.6 +/- 9.6 ms, n = 160, P < 0.001). The present results provide valuable information about the threshold, frequency tuning characteristics, minimal response latency, and duration selectivity of OFF neurons in the auditory thalamus.

Acoustic Stimulation↗

Spinal and medullary lamina I projection to nucleus submedius in medial thalamus: a possible pain center.

1. Results obtained with the anterograde horseradish peroxidase (HRP) and autoradiographic techniques have revealed a dense and compact spinal and trigeminal projection to the dorsal portion of the nucleus submedius (Sm) in the medial thalamus of the cat. A homologous projection was observed in two cases in the monkey and in three cases in the rat with the anterograde HRP method. 2. The projection to Sm in topographically organized rostrocaudally, with trigeminal terminations located caudally and spinal terminations rostrally. The rostrocaudal extent of the trigeminal field in Sm (ca. 1 mm) is larger than that of the spinal field (ca. 0.8 mm). There is a considerable ipsilateral trigeminal projection, whereas there is a minimal uncrossed spinal projection to Sm. 3. Retrogradely labeled cells were analyzed in cases with small injections of HRP in medial thalamus in the cat. The results indicate that the projections to Sm identified in the anterograde experiments arise from lamina I cells of the spinal and medullary dorsal horm, probably exclusive of lamina V and other spinothalamic cells. The retrograde results corroborate the topographic observations made in the anterograde experiments. 4. These results suggest that Sm may be critically involved in specific nociception.

Animals↗

Neurons in ventrobasal region of cat thalamus selectively responsive to noxious mechanical stimulation.

1. A survey was made of neurons located in the ventral posterior lateral nucleus of the cat thalamus and its immediate vicinity for elements with specifically nociceptive properties. 2. Pipette microelectrodes filled with a dye solution were used to obtain extracellular recordings of unitary activity in 34 animals anesthetized with chloralose. 3. The great majority of the over 1,000 different single units responding to sciatic nerve stimulation noted in this series of experiments could also be excited by innocuous mechanical stimulation of skin or subcutaneous tissues. An infrequent but consistently noted group of units excited by A-alpha beta delta sciatic nerve volleys did not respond to innocuous mechanical manipulation or A-alpha beta sciatic nerve volleys; they were excited only by either noxious levels of mechanical stimulation or when volleys included the activity of more slowly conducting myelinated fibers. The latencies of such "high-threshold" units to sciatic volleys were longer than those of the other units. 4. Histologically identified recording sites marked by dye were recovered for 17 high-threshold units. Twelve of the 17 could be excited by noxious manipulations of restricted parts of the contralateral hindlimb. Nine of the 12 had cutaneous receptive fields, whereas 3 responded only to stimulation of subcutaneous tissues. None of the 17 high-threshold units evidenced additional discharges that could be correlated with the C-fiber component of sciatic nerve volleys. 5. The high-threshold units typically exhibited a low level of irregular background activity, which increased on repeated noxious stimulation of the peripheral receptive fields. Tactile units of the same or adjacent penetrations usually had a much greater degree of ongoing activity, often marked by bursts at a relatively high frequency. 6. The recording sites for the 17 high-threshold neurons were located dorsal and ventrolateral to the core of the ventrobasal nuclei and were not found in the midst of the low-threshold, cutaneous, mechanoreceptive population. During vertical stereotaxic penetrations, high-threshold units were noted dorsal or ventral to the location of ventrobasal tactile units in a pattern consistent with the core's somatotopic arrangement. 7. These results support the concept that the cat ventrolateral thalamus receives a small but distinct selectively nociceptive projection. The nociceptive neurons appear to be located in a shell that surrounds the main tactile projection to the ventral posterior lateral nucleus and that retains at least part of the topographic arrangement characteristic of the tactile core. Presumably, this projection is part of an organization identifying and localizing noxious stimulation.

Animals↗

Neural coding of gustatory information in the thalamus of Macaca mulatta.

1. Extracellular action potentials were recorded from single neurons in the parvicellular division of the ventroposteromedial (VPMpc) nucleus of the thalamus of restrained, but alert, Old World monkeys during gustatory, tactile, and thermal stimulation of the oral cavity. In contrast to previous reports in anesthetized or paralyzed rats, the spontaneous activity of these neurons was brisk and their evoked responses robust. 2. Each of 50 taste-responsive neurons was tested with 1.0 M sucrose, 0.1 M NaCl, 0.003 M HCl, and 0.001 M QHCl before other concentrations of the same stimuli were used. Sucrose, which was effective in 80% of the neurons tested, evoked the largest responses of the 4 standard gustatory stimuli (16.1 spikes/s). The average response to NaCl, an effective stimulus for 44% of the neurons in the sample, was 7.5 spikes/s. HCl and QHCl, which few neurons responded to, typically evoked smaller responses. 3. Most of the neurons tested showed monotonic intensity-response (I-R) functions. The power functions showed about the same degree of compression (range = 0.39-0.53), which has been described previously for brain stem neurons in anesthetized rodents. Only 9.1% of the responses were inhibitory, and there was no tendency for these responses to be associated with either specific neurons or stimuli. These data suggest that quality coding of gustatory information in the thalamus is not radically different from that seen among lower-order neurons in other species. 4. Through the use of hierarchical cluster analysis, it was possible to divide the neuron sample into 2 groups, one of which consisted of sucrose-best neurons that had an average entropy value of 0.56. The neurons in the other group, though more heterogeneous, showed either primary or side-band sensitivity to NaCl. The average breadth of responsiveness of the 50 thalamic neurons as described by the entropy coefficient was 0.73. 5. In addition to gustatory neurons, tactile (n = 15), thermal (n = 1), and nonresponsive (n = 25) neurons also were located within VPMpc. An additional 48 neurons that could not be classified as either sensory or motor in nature, inhibited their bursting spontaneous discharge just prior to the onset of fluid stimulation. Only 2 of these neurons demonstrated differential chemical sensitivity. The presence of these nongustatory neurons within the thalamic taste area suggests that the traditional characterization of VPMpc as a gustatory relay may understate its role in ingestive behavior and ignore other noningestive functions of the area.

Animals↗

Effects of metabotropic glutamate receptor activation in auditory thalamus.

Metabotropic glutamate receptors (mGluRs) are expressed predominantly in dendritic regions of neurons of auditory thalamus. We studied the effects of mGluR activation in neurons of the ventral partition of medial geniculate body (MGBv) using whole cell current- and voltage-clamp recordings in brain slices. Bath application of the mGluR-agonist, 1S,3R-1-aminocyclopentan-1,3-dicarboxylic acid or 1S,3R-ACPD (5-100 microM), depolarized MGBv neurons (n = 67), changing evoked response patterns from bursts to tonic firing as well as frequency responses from resonance ( approximately 1 Hz) to low-pass filter characteristics. The depolarization was resistant to Na(+)-channel blockade with tetrodotoxin (TTX; 300 nM) and Ca(2+)-channel blockade with Cd(2+) (0.1 mM). The application of 1S, 3R-ACPD did not change input conductance and produced an inward current (I(ACPD)) with an average amplitude of 84.2 +/- 5.3 pA (at -70 mV, n = 22). The application of the mGluR antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine (0.5 mM), reversibly blocked the depolarization or I(ACPD). During intracellular application of guanosine 5'-O-(3-thiotriphosphate) from the recording electrode, bath application of 1S,3R-ACPD irreversibly activated a large amplitude I(ACPD). During intracellular application of guanosine 5'-O-(2-thiodiphosphate), application of 1S, 3R-ACPD evoked only a small I(ACPD). These results implicate G proteins in mediation of the 1S,3R-ACPD response. A reduction of external [Na(+)] from 150 to 26 mM decreased I(ACPD) to 32.8 +/- 10. 3% of control. Internal applications of a Ca(2+) chelator, 1, 2-bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA; 10 mM), suppressed I(ACPD), implying a contribution of a Ca(2+) signal or Na(+)/Ca(2+) exchange. However, partial replacement of Na(+) with Li(+) (50 mM) did not significantly change I(ACPD). Therefore it seemed less likely that a Na(+)/Ca(2+) exchange current was a major participant in the response. A reduction of extracellular [K(+)] from 5.25 to 2.5 mM or external Ba(2+) (0.5 mM) or Cs(+) (2 mM) did not significantly change I(ACPD) between -40 and -85 mV. Below -85 mV, 1S,3R-ACPD application reversibly attenuated an inward rectification, displayed by 11 of 20 neurons. Blockade of an inwardly rectifying K(+) current with Ba(2+) (1 mM) or Cs(+) (2-3 mM) occluded the attenuation. In the range positive to -40 mV, 1S, 3R-ACPD application activated an outward current which Cs(+) blocked; this unmasked a voltage dependence of the inward I(ACPD) with a maximum amplitude at approximately -30 mV. The I(ACPD) properties are consistent with mGluR expression as a TTX-resistant, persistent Na(+) current in the dendritic periphery. We suggest that mGluR activation changes the behavior of MGBv neurons by three mechanisms: activation of a Na(+)-dependent inward current; activation of an outward current in a depolarized range; and inhibition of the inward rectifier, I(KIR). These mechanisms differ from previously reported mGluR effects in the thalamus.

Animals↗

Segregation of nociceptive and non-nociceptive networks in the squirrel monkey somatosensory thalamus.

The somatosensory thalamus (here we examine neurons in the caudal cutaneous portion of ventral posterior lateral nucleus, VPL) is composed of a somatotopic arrangement of anteroposteriorly oriented rods. Each rod is a collection of neurons with homogeneous properties that relay sensory information to specific cortical columns. We developed a multi-electrode recording technique, using fixed-geometry four-tip electrodes that allow simultaneous recordings from small populations of neurons (4-11), in a approximately 150 x 150 x 150 micrometer(3) volume of brain tissue (i.e., the approximate diameter of rods) and study of their spatiotemporal interactions. Due to the fixed geometry of the four-tip electrodes, the relative locations of these neurons can be determined, and due to the simultaneity of the recordings, their spike-timing coordination can be calculated. With this method, we demonstrate the existence of two distinct functional networks: nociceptive and non-nociceptive networks. The population dynamics of these two types of networks are different: cross-correlations in each type of network were different in direction and strength, were a function of the distance between neurons, had an opponent organization for nociceptive networks and a non-opponent organization for non-nociceptive networks, and rapidly changed under different stimulus conditions independent of changes in firing rates. A simple neural network model mimicked these physiological findings, demonstrating the necessity of inhibitory interneurons and different amounts of afferent input synchronization. Based on these results, we conclude that the somatosensory thalamus is composed of two modules, nociceptive and non-nociceptive rods, and that the response dynamics differences between these modules are due to spatiotemporal differences of their afferent inputs.

Action Potentials↗

Modulatory effect of cortical activation on the lemniscal auditory thalamus of the Guinea pig.

In the present study, we investigated the point-to-point modulatory effects from the auditory cortex to the thalamus in the guinea pig. Corticofugal modulation on thalamic neurons was studied by electrical activation of the auditory cortex. The modulation effect was sampled along the frontal or sagittal planes of the auditory thalamus, focusing on the ventral division (MGv) of the medial geniculate body (MGB). Electrical activation was targeted at the anterior and dorsocaudal auditory fields, to which the MGv projects and from which it assumptively receives reciprocal projections. Of the 101 MGv neurons examined by activation of the auditory cortex through passing pulse trains of 100-200 microA current into one after another of the three implanted electrodes (101 neurons x 3 stimulation sites = 303 cases), 208 cases showed a facilitatory effect, 85 showed no effect, and only 10 cases (7 neurons) showed an inhibitory effect. Among the cases of facilitation, 63 cases showed a facilitatory effect >100%, and 145 cases showed a facilitatory effect from 20-100%. The corticofugal modulatory effect on the MGv of the guinea pig showed a widespread, strong facilitatory effect and very little inhibitory effect. The MGv neurons showed the greatest facilitations to stimulation by the cortical sites, with the closest correspondence in BF. Six of seven neurons showed an elevation of the rate-frequency functions when the auditory cortex was activated. The comparative results of the corticofugal modulatory effects on the MGv of the guinea pig and the cat, together with anatomical findings, hint that the strong facilitatory effect is generated through the strong corticothalamic direct connection and that the weak inhibitory effect might be mainly generated via the interneurons of the MGv. The temporal firing pattern of neuronal response to auditory stimulus was also modulated by cortical stimulation. The mean first-spike latency increased significantly from 15.7 +/- 5.3 ms with only noise-burst stimulus to 18.3 +/- 4.9 ms (n = 5, P < 0.01, paired t-test), while the auditory cortex was activated with a train of 10 pulses. Taking these results together with those of previous experiments conducted on the cat, we speculate that the relatively weaker inhibitory effect compared with that in the cat could be due to the smaller number of interneurons in the guinea pig MGB. The corticofugal modulation of the firing pattern of the thalamic neurons might enable single neurons to encode more auditory information using not only the firing rate but also the firing pattern.

Acoustic Stimulation↗

Application of magnetic resonance imaging in functional stereotactic thalamotomy for the evaluation of individual variations of the thalamus.

An application of MRI in functional stereotactic thalamotomy is presented. To estimate the individual anatomic variations of the thalamus prior to stereotactic thalamotomy, a special study using a proton density image that shows myeloarchitectonic features of the thalamus was performed. The proton density MRI was demonstrated to be very useful to determine the safest trajectory and tentative target point. However, as a detailed functional localization of the thalamic subnuclei cannot be yet obtained by MRI, the final target should be decided on the basis of electrophysiological findings.

Adult↗

The distribution fields of sensory neurons in the human thalamus.

Thalamic neurons were identified by activity related to passive joint movement, active joint movement, tapping stimulation, and light touch stimulation during surgery to treat movement disorders. The neurons were classified into three types: movement-related neurons, tapping-related neurons, or superficial sensory neurons. Tapping-related neurons had characteristics of lemniscal sensory neurons and occupied the border area of movement-related neurons and superficial sensory neurons. Tapping-related neurons showed a laminar distribution 1.0-1.5 mm in width in the anterodorsal region of the nucleus ventrocaudalis. Results suggest that the distribution pattern of tapping-related neurons in the human thalamus is consistent with the functional distribution pattern found in the monkey thalamus.

Brain Mapping↗

What goes on in the motor thalamus?

Physiological observations made in man offer a unique opportunity to understand the motor thalamus. On the one hand, the patient can describe what he feels when a site is stimulated; on the other, one can observe any induced motor effect, both in 'normal' patients and in those with movement disorders. Finally, all this can be correlated with single unit recordings at the same site. Data has been correlated relative to the motor thalamus from over 10,000 macrostimulation sites and from 114 patients undergoing microstimulation and microrecording, in an attempt to understand something of the function of this part of the brain.

Electric Stimulation↗

Combined electrical stimulation of the periaqueductal gray matter and sensory thalamus.

11 patients with chronic intractable pain of at least 3 years' duration underwent a morphine infusion test, the results of which suggested a syndrome of superimposed somatogenic and neurogenic pain components. They then underwent stereotactic implantation of a dual-channel brain stimulation system with two brain electrodes, one in the left periaqueductal gray matter (PAG) and the other in the sensory thalamus contralateral to the neurogenic pain. Using this system, all patients have obtained excellent simultaneous relief of both pain components (follow-up 12-36 months). The findings support a notion of two separate sensory modulating systems. They indicate that combined electrical stimulation of the PAG and sensory thalamus is a technically feasible and clinically satisfactory modality for the control of pain in humans, and they appear to indicate that better pain control is obtained by continuous, cycled stimulation of the PAG than by the conventional mode of stimulation.

Electric Stimulation Therapy↗

Correlation between the neural noise in the thalamus after cerebrovascular disease and computerized tomography. A case report.

The case is presented of a 45-year-old man who suffered from a sudden attack of unconsciousness with right hemiplegia and later developed a spastic hemiparesis accompanied by involuntary movement of the right upper limb. CT scan revealed an old putaminal hemorrhage and almost intact thalamus, but neural noise recordings during the stereotactic thalamotomy of this case showed marked decrease of the neural activity in the thalamus suggesting some functional changes.

Cerebral Hemorrhage↗