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Changes in protein synthesis and calcium homeostasis in the thalamus of spontaneously hypertensive rats with focal cerebral ischemia.

The thalamus has been shown to undergo secondary degeneration after cerebrocortical ischemia. However, little is known about the time course of the retrograde thalamic degeneration. The present study was designed to investigate time-dependent changes in the morphology, protein synthesis and calcium metabolism of thalamic neurons in middle cerebral artery (MCA)-occluded spontaneously hypertensive stroke-prone rats that showed primary focal ischemia in the temporoparietal cortex after permanent occlusion of the left distal MCA. In the histologic study by light and electron microscopy, swelling of the nucleus and shrinkage of the perikarya were seen in some neurons of the ventroposterior (VP) thalamic nucleus on the lesioned side at 5 days after ischemia. At the same time, the incorporation of radiolabeled leucine in VP thalamic neurons began to decrease significantly with concomitant a decrease in the number of polyribosomes in the neurons. Conspicuous 45Ca accumulation was noted at 3 days after ischemia and persisted up to 1 month in the VP thalamic nucleus on the lesioned side. These findings suggest that the secondary thalamic degeneration after cortical infarction starts with disruption of calcium homeostasis in situ at the third day after MCA occlusion, followed by a decrease in polyribosomes but not by disaggregation of polyribosomes as seen in hippocampal CA1 neurons subjected to transient forebrain ischemia.

Animals↗

A comparison of CNS angiotensin II binding in the hypothalamus-thalamus-septum-midbrain region of developing spontaneously hypertensive and normotensive rats.

Specific angiotensin II (ANG II) binding was studied in brain homogenates from the hypothalamus-thalamus-septum-midbrain (HTSM) region of age-matched 4-, 8-, 12- and 16-week spontaneously hypertensive rats (SHR) and their normotensive controls, Wistar-Kyoto (WKY) rats, using 125I-angiotensin II. Scatchard analysis revealed that the dissociation constants (Kd) ranged from 0.36 to 0.73 nmol/l, although these values were not significantly different at any given age period between the SHR and WKY rats. In contrast, a statistically significant increase in ANG II receptor binding was seen between the SHR and WKY rat at 4 weeks of age. However, this difference was not observed at older age periods. Furthermore, both the SHR and WKY rat showed a decrease in ANG II receptor levels during development, with the most marked reductions occurring between 12 and 16 weeks of age for both strains. These findings suggest that ANG II receptors in the HTSM region of both the SHR and WKY rat are down-regulated during development, that receptor loss is more significant in the SHR than in its normotensive control and that binding capacity differences between the two strains are only seen before the onset of measureable increases in the arterial pressure of the SHR. We conclude that there is a significant difference in the ANG II binding capacity during the development of hypertension in the SHR as compared with the WKY rat and therefore it may play a role in the pathogenesis of this disorder.

Angiotensin II↗

The role of the thalamus in the flow of information to the cortex.

The lateral geniculate nucleus is the best understood thalamic relay and serves as a model for all thalamic relays. Only 5-10% of the input to geniculate relay cells derives from the retina, which is the driving input. The rest is modulatory and derives from local inhibitory inputs, descending inputs from layer 6 of the visual cortex, and ascending inputs from the brainstem. These modulatory inputs control many features of retinogeniculate transmission. One such feature is the response mode, burst or tonic, of relay cells, which relates to the attentional demands at the moment. This response mode depends on membrane potential, which is controlled effectively by the modulator inputs. The lateral geniculate nucleus is a first-order relay, because it relays subcortical (i.e. retinal) information to the cortex for the first time. By contrast, the other main thalamic relay of visual information, the pulvinar region, is largely a higher-order relay, since much of it relays information from layer 5 of one cortical area to another. All thalamic relays receive a layer-6 modulatory input from cortex, but higher-order relays in addition receive a layer-5 driver input. Corticocortical processing may involve these corticothalamocortical 're-entry' routes to a far greater extent than previously appreciated. If so, the thalamus sits at an indispensable position for the modulation of messages involved in corticocortical processing.

Animals↗

The thalamus as a monitor of motor outputs.

Many of the ascending pathways to the thalamus have branches involved in movement control. In addition, the recently defined, rich innervation of 'higher' thalamic nuclei (such as the pulvinar) from pyramidal cells in layer five of the neocortex also comes from branches of long descending axons that supply motor structures. For many higher thalamic nuclei the clue to understanding the messages that are relayed to the cortex will depend on knowing the nature of these layer five motor outputs and on defining how messages from groups of functionally distinct output types are combined as inputs to higher cortical areas. Current evidence indicates that many and possibly all thalamic relays to the neocortex are about instructions that cortical and subcortical neurons are contributing to movement control. The perceptual functions of the cortex can thus be seen to represent abstractions from ongoing motor instructions.

Afferent Pathways↗

Colour through the thalamus.

Visual perception in humans and other primates depends on the retino-thalamo-cortical pathway. This pathway begins with retinal ganglion cells, which have axonal terminations in the lateral geniculate nucleus (LGN) of the thalamus. Each ganglion cell axon provides input to one or more LGN relay neurones and, in turn, nearly all the LGN relay neurones project to the primary visual cortex. Thus, this pathway forms the dominant functional input to cortical mechanisms for colour vision, as well as for other aspects of conscious visual perception. In this review, recent progress in understanding the transmission of signals for colour vision through the LGN is summarised, with emphasis on studies which provide links between function and structure.

Animals↗

Development of the pathway from the reticular and perireticular nuclei to the thalamus in ferrets: a Dil study.

This study examines the connections of the thalamic reticular and perireticular cell groups in developing ferrets. Small crystals of Dil (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) were implanted into either the dorsal thalamus or the cerebral cortex of aldehyde-fixed prenatal and postnatal ferret brains. A small implant of Dil into the presumptive lateral geniculate nucleus during early prenatal development [between embryonic day 23 (E23) and E25] reveals many retrogradely labelled cells in the reticular nucleus. At E40, just before birth, the number of cells retrogradely labelled in the reticular nucleus has become reduced compared to earlier prenatal implants, whether from small or large implants of Dil into the lateral geniculate nucleus. By postnatal day 7, an adult-like pattern of retrograde labelling is seen in the reticular nucleus; at this age, a small implant of Dil limited to the lateral geniculate nucleus retrogradely labels a discrete group of cells located in the caudal regions of the reticular nucleus. In the internal capsule, adjacent to the reticular nucleus, there are two distinct groups of neurons. One group, called the large-celled perireticular zone (LPR), enters the internal capsule very early in development (from E25; Mitrofanis, J., Eur. J. Neurosci., 6, 253-263, 1994) and is not labelled from the lateral geniculate nucleus at any developmental stage. Small implants of Dil into presumptive visual and somatosensory cortices shows that the LPR lies in a distinct region of the primordial internal capsule. Corticothalamic and thalamocortical axons turn sharply in the region of the LPR, whilst corticospinal and corticobulbar axons pass straight through the LPR on towards their more caudal targets. Later, after both sets of axons have reached their targets, the LPR is not seen in the internal capsule. The other group of cells in the internal capsule, called the small-celled perireticular zone (SPR), forms a distinct band of cells lying midway between the reticular nucleus and the globus pallidus. These cells enter the internal capsule much later in development, at about E40. Unlike the cells in the LPR, cells in the SPR are retrogradely labelled after an implant of Dil into the lateral geniculate nucleus, and there are many which remain in the adult (Clemence, A. E. and Mitrofanis, J., J. Comp. Neurol., 322, 167-181, 1992).

Aging↗

The axonal arborization of single thalamic reticular neurons in the somatosensory thalamus of the rat.

This study describes the axonal projections of single neurons of the thalamic reticular complex within the somatosensory thalamic nuclei in rats. Experiments were performed under urethane anaesthesia and reticular cells were labelled by extracellular microiontophoretic applications of biocytin. The axonal arborization of 25 thalamic reticular cells projecting to the ventrobasal (VB) nucleus and/or to the posterior thalamic (Po) complex were reconstructed from serial horizontal sections. Reticular cells labelled with biocytin display somatodendritic features similar to those reported previously. Their cell body is fusiform and their dendrites bear few spines and show a high degree of streaming along the horizontal curved axis of the nucleus. In most cells, axon-like beaded processes stem out from dendrites but, contrary to previous descriptions, no intrareticular axonal collateral was observed. The axonal arborization of most thalamic reticular cells is confined within the limits of a single thalamic nucleus; only two neurons were seen projecting to both the VB and the Po nuclei. In VB, termination fields form short rods (diameter approximately 150 microns, length approximately 200-300 microns) densely packed with grape-like boutons and varicosities; termination fields in Pro are larger, much less dense, and they are contained within a horizontal slab of tissue (thickness approximately 200 microns, mediolateral width approximately 400 microns, rostrocaudal length approximately 1 mm. By charting the position of all labelled cells within the thickness of the thalamic reticular complex, a strip-like arrangement was revealed. Cells projecting to Po occupy the innermost portion of the nucleus whereas those projecting to the ventral-posteromedial and ventral-posterolateral nuclei are located respectively in the middle and in the outer tiers of the nucleus. This strip-like reciprocity was confirmed by separate biocytin injections performed in VB and in Po. These results show that inhibition of reticular origin is distributed within the rat dorsal thalamus in a highly specific manner, most likely according to a principle of reciprocity within the somatotopic representation of the body.

Animals↗

Both oral and caudal parts of the spinal trigeminal nucleus project to the somatosensory thalamus in the rat.

Recent evidence has been accumulated that not only spinal trigeminal nucleus caudalis (Sp5C) neurons but also spinal trigeminal nucleus oralis (Sp5O) neurons respond to noxious stimuli. It is unknown, however, whether Sp5O neurons project to supratrigeminal structures implicated in the sensory processing of orofacial nociceptive information. This study used retrograde tracing with Fluorogold in rats to investigate and compare the projections from the Sp5O and Sp5C to two major thalamic nuclei that relay ascending somatosensory information to the primary somatic sensory cortex: the ventroposteromedial thalamic nucleus (VPM) and the posterior thalamic nuclear group (Po). Results not only confirmed the existence of contralateral projections from the Sp5C to the VPM and Po, with retrogradely labelled neurons displaying a specific distribution in laminae I, III and V, they also showed consistent and similar numbers of retrogradely labelled cell bodies in the contralateral Sp5O. In addition, a topographic distribution of VPM projections from Sp5C and Sp5O was found: neurons in the dorsomedial parts of Sp5O and Sp5C projected to the medial VPM, neurons in the ventrolateral Sp5O and Sp5C projected to the lateral VPM, and neurons in intermediate parts of Sp5O and Sp5C projected to the intermediate VPM. All together, these data suggest that not only the Sp5C, but also the Sp5O relay somatosensory orofacial information from the brainstem to the thalamus. Furthermore, trigemino-VPM pathways conserve the somatotopic distribution of primary afferents found in each subnucleus. These results thus improve our understanding of trigeminal somatosensory processing and help to direct future electrophysiological investigations.

Animals↗

Dissociable memory effects after medial thalamus lesions in the rat.

Variable neuropathology in cases of diencephalic amnesia has led to uncertainty in identifying key thalamic nuclei and their potential role in learning and memory. Based on the principal neural connections of the medial thalamus, the current study tested the hypothesis that different aggregates of thalamic nuclei contribute to separate memory systems. Lesions of the anterior thalamic aggregate (AT), which comprises the anterodorsal, anteromedial and anteroventral nuclei produced substantial deficits in both working and reference spatial memory in a radial arm maze task in rats, supporting the view that the AT is an integral part of a hippocampal memory system. Lesions to the lateral thalamic aggregate (LT), which comprises the intralaminar nuclei (centrolateral, paracentral and rostral central medial nuclei) and lateral mediodorsal thalamic nuclei (lateral and paralamellar nuclei) produced a mild working memory impairment only, while lesions to the posteromedial thalamic aggregate (MT), which comprises the central and medial mediodorsal thalamic nuclei and the intermediodorsal nucleus had no effect on radial arm maze performance. In contrast, only MT lesions impaired learning associated with memory for reward value, consistent with the idea that the MT contributes to an amygdala memory system. Compared with chance discrimination, the control and AT groups, but not MT or LT groups, showed evidence for temporal order memory for two recently presented objects; all groups showed intact object recognition for novel vs. familiar objects. These new dissociations show that different medial thalamic aggregates participate in multiple memory systems and reinforce the idea that memory deficits in diencephalic amnesics may vary as a function of the relative involvement of different thalamic regions.

Animals↗

Posttraining lesions of the auditory thalamus, but not cortex, disrupt the inhibition of fear conditioned to an auditory stimulus.

The purpose of this study was to examine the effects of lesions within the auditory system in an effort to disrupt the processing of the noise stimulus conditioned to inhibit fear. To accomplish this, three experiments were conducted in which rats were first given feature-negative discrimination training in which a noise was conditioned to inhibit fear to a light that signals danger. Following training, rats were given lesions of the medial geniculate body (MGB), auditory thalamus (ADT), or auditory cortex (CTX). Next, rats were tested for the ability to inhibit fear in the presence of the noise safety signal. The results of these experiments indicated that bilateral lesions of ADT disrupted the ability of the noise inhibitor to inhibit fear. In contrast, lesions largely restricted to the MGB or CTX did not disrupt the inhibition of fear. Along with past studies, these results suggest that an auditory pathway(s), which includes projections from the tectum to the ADT, is used to detect the safety properties previously conditioned to an auditory stimulus.

Acoustic Stimulation↗

Desmethylimipramine enhances the release of endogenous GABA and other neurotransmitter amino acids from the rat thalamus.

The influence of desmethylimipramine (DMI) on the release of endogenous gamma-aminobutyric acid (GABA) and some other amino acids from the rat thalamus was studied with a push-pull perfusion technique. Following HPLC the amino acids were fluorimetrically estimated. Added to the perfusion medium at a concentration of 10 mumol L-1, DMI caused a 5- to 10-fold increase in the release of GABA. Similar effects were found with imipramine, trimeprimine, haloperidol, and propranolol. The elevation of GABA release induced by DMI was Ca dependent. The release of aspartate and glutamate was also increased by DMI, but in contrast to K ions, DMI did not reduce the thalamic output of glutamine.

Amino Acids↗

Real-time monitoring of electrically stimulated norepinephrine release in rat thalamus: I. Resolution of transmitter and metabolite signal components.

Electrical stimulation of an ascending path of the locus ceruleus-norepinephrine system was used to elicit release of norepinephrine at noradrenergic terminal fields of the rat thalamus. Overflow into the extracellular fluid space was measured by fast in vivo chronoamperometry. At pretreated carbon fibers, the electrochemical signal consists of a sharp peak of approximately 20-30 s duration followed by a slower, plateau-like decay to baseline. The peak, characterized by a variety of pharmacological manipulations and dialysis perfusion, is primarily due to norepinephrine. The plateau was shown to correspond to metabolite efflux of 3,4-dihydroxy-phenylacetic acid. By varying the degree of electrochemical pretreatment, the response time and sensitivity of the fibers can be tuned to follow the entire signal or to select the separate components for detailed evaluation. This approach can be used to provide new information on the spatial and temporal characteristics of stimulated neurotransmitter release.

3,4-Dihydroxyphenylacetic Acid↗

Compulsive gnawing in rats after implantation of drugs into the ventral thalamus. A contribution to the mechanism of morphine action.

1 Implantation of morphine into various parts of the corpus striatum of rats evokes only weak gnawing responses.2 Deposition of apomorphine, morphine or methadone in the region of the nucleus ventralis thalami produces a biphasic response, i.e. general excitation, followed by a period of intense gnawing.3 The effect of both apomorphine and morphine is blocked by chlorpromazine, haloperidol and pimozide. However, pretreatment with alpha-methyltyrosine methyl ester or alpha-methyldopa prevents only the gnawing response to morphine, but not to apomorphine.4 Systemic nalorphine, morphine or pethidine suppress the gnawing response, evoked by thalamic implants of apomorphine or morphine.5 Systemic amphetamine potentiates the effect of thalamic deposits of morphine.6 Compulsive gnawing, following implantation of morphine into the ventral region of the thalamus, probably results from enhanced production and release of catecholamines.

Amphetamine↗

Hyperperfusion of cerebral cortex, thalamus and basal ganglia during spontaneously occurring migraine headaches.

Color-coded, cross-sectional imaging of local cerebral blood flow (LCBF) was made in a prospective manner among 22 patients with well-established common or classic migraine utilizing the stable xenon-enhanced computed tomographic (Xe CT-CBF) method. LCBF in patients during spontaneously occurring headaches (N = 12) were significantly higher compared to patients without headache (N = 10) by 25-35%. The hyperperfusion involved not only cerebral cortex but also subcortical structures including thalamus, basal ganglia, and subcortical white matter. LCBF increases were not bilateral and sometimes asymmetrical, but LCBF increases were not consistently related to the preponderant side of headache. No significant differences were observed in the degree or pattern of cerebral hyperperfusion during headaches compared among common (N = 6) and classic (N = 6) migraineurs. Results suggest a common etiology for both common and classic migraine. Results are not consistent with spreading oligemia or spreading cortical depression as a cause of migraine. The cerebral hyperperfusion appears to be mediated by various neurogenic and chemical changes accompanying migraine. The unilateral nature of migraine head pain is more likely due to dilation of extracranial vessels.

Adult↗

Somatotopic organization of vibrissal responses in the ventro-basal complex of the rat thalamus.

1. The region of the ventro-basal complex (VB) of the thalamus responding to movements of the whiskers has been mapped electrophysiologically in rats under either urethane or barbiturate anaesthesia.2. Whisker responses were found in the dorso-medial part of VB throughout its rostro-caudal extent; they occupied one third to one half of the total VB region.3. Most cells responded to movements of only one whisker and the responses were somatotopically organized. The different horizontal lines of whiskers were represented at different rostro-caudal levels within the nucleus, the most dorsal line being represented most caudally. At each level the larger, more caudal whiskers were represented more dorsally and laterally than the smaller, more rostral whiskers.

Animals↗

The responses of cells in the rat thalamus to mechanical movements of the whiskers.

1. The responses of single cells to mechanical movements of individual whiskers have been recorded from the ventro-basal complex of the thalamus, in rats under urethane or barbiturate anaesthesia.2. With ramp-shaped displacements of a whisker above a critical velocity, the cells gave a short latency response of 1-5 impulses, while with sinusoidal movement (1-35 Hz) they usually responded with 1-2 impulses per cycle.3. The cells did not respond to maintained deflexions of a whisker. Small static displacements did not modify the response to a superimposed movement; larger static displacements reduced or abolished the response.4. Three-quarters of the cells were found to be particularly sensitive to movements in one quadrant (90 degrees or less). For any one cell, there was no obvious relationship between the most sensitive direction and the position of the whisker on the face.5. The ramp amplitude appeared to have little effect on the response. However, increases in ramp velocity decreased the response latency and, in some cells, increased the number of impulses per ramp.6. Other studies have shown that most afferent nerve fibres from whiskers give slowly adapting responses and the possible modification of these thalamic responses, by anaesthesia, is discussed.

Action Potentials↗

Neurones in the ventrobasal complex of the rat thalamus responding to scrotal skin temperature changes.

1. In rats the scrotal temperature was raised or lowered with a water-perfused thermode while micro-electrode recordings were made of unit activity in the ventrobasal complex of the thalamus. The electrodes were aimed at the region where evoked responses had been found by electrical stimulation of the scrotum. Recording sites were marked by iontophoresis of dye from the micro-electrode.2. Changes in firing rate of thalamic neurones were only found in the scrotal temperature range of 31-40 degrees C. Within this range, 72% of the 123 cells tested were excited or suppressed by skin warming. At temperatures above or below this range, activity was not affected. Most of the cells responded just to temperature and only 7% were also excited by touch.3. Raising temperature in the range 31-40 degrees C caused 82% of the thermally responding cells to increase their firing rate and 18% to decrease their rate. Individual neurones showed a sudden and maintained change in their activity for scrotal temperature increases of only 2, 1 or even 0.5 degrees C. Mean firing rates changed by factors of about 8 or more with these temperature increases and further warming did not change the rate. These step-like changes in firing rate were found at different points over the whole skin temperature range of 31-40 degrees C, but most were between 33 and 38 degrees C.4. For a given neurone the step-like change in activity occurred once its critical temperature was reached, irrespective of whether this was achieved by a step increase of skin temperature over 1-2 sec or by a slow ramp increase lasting several minutes.5. It is not possible to say whether the skin warm receptors, cold receptors or both were responsible for these thalamic responses, but the results do show that incoming thermal information is considerably processed when it reaches the thalamic level.

Animals↗

Excitatory amino acid receptors and synaptic transmission in the rat ventrobasal thalamus.

1. Extracellular single-neurone recordings were made in the ventrobasal thalamus (v.b.t.) of urethane-anaesthetized rats with multi-barrel ionophoretic electrodes in order to test the hypothesis that excitatory amino acid receptors are involved in the responses of these neurones to stimulation of sensory afferents. 2. Responses of neurones to either physiological stimulation of hair and vibrissa follicle sensory afferents and to ionophoretically applied excitatory amino acids were challenged with the antagonists D-2-amino-5-phosphonovalerate (APV), kynurenate and gamma-D-glutamylaminomethyl sulphonate (GAMS). 3. In agreement with previous findings in other brain areas, ionophoretically applied APV was found to selectively antagonize responses of v.b.t. neurones to N-methylaspartate (NMA), whereas GAMS was found to be moderately kainate selective. Kynurenate was found to be relatively non-selective. 4. Responses of neurones to short-duration (10-20 ms) physiological stimulation of afferents were resistant to APV when this antagonist was applied with NMA-selective ionophoretic currents. In contrast, these APV currents were adequate to antagonize responses to maintained physiological stimulation. 5. The broad spectrum excitatory amino acid antagonist kynurenate was found to block synaptic responses of v.b.t. neurones to both short-duration and maintained stimuli when it was applied with currents which were sufficient to reduce responses to ionophoretic quisqualate. 6. GAMS was found to selectively block kainate responses in a proportion of the neurones tested. In such cases, there was little effect of the antagonist on the responses evoked by either short-duration or maintained sensory stimuli. 7. It is concluded that excitatory amino acid receptors of both the NMDA and non-NMDA type are involved in the synaptic responses of v.b.t. neurones to sensory afferent stimulation, and that the apparent synaptic pharmacology depends on the mode of stimulation of the afferent pathway.

2-Amino-5-phosphonovalerate↗