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Dual projections of single cholinergic and aminergic brainstem neurons to the thalamus and basal forebrain in the rat.

Compelling evidence indicates that cholinergic basal forebrain neurons are strongly activated during waking, and concurrently thalamic spindle activity is suppressed and thalamocortical sensory transmission is facilitated. Both thalamus and basal forebrain are known to receive projections from brainstem cholinergic and aminergic neuronal pools that are involved in wake/sleep regulation. The present study addressed the question of whether single cholinergic and aminergic neurons contributed to both of these ascending projections, by using two fluorescent retrograde tracers combined with immunofluorescence. Cholinergic neurons projecting to both the basal forebrain and thalamus were found in the pedunculopontine and laterodorsal tegmental nuclei, representing an average of 8.0% of the total cholinergic cell population in these nuclei. Serotonergic neurons with dual projections were observed in the dorsal, median and caudal linear raphe nuclei, accounting for a mean of 4.7% of total serotonergic neurons in these nuclei. Relatively few noradrenergic neurons (2.0%) in the locus ceruleus projected to both target structures, and a very small subpopulation of histaminergic neurons (1.5%) in the tuberomammillary hypothalamic nucleus had dual projections. Of all brainstem neurons with dual projections, cholinergic and serotonergic neurons accounted for an overwhelming majority, with noradrenergic followed by histaminergic neurons representing the remaining minority. These data suggest that through dual projections, cholinergic and aminergic brainstem neurons can concurrently modulate the activity of neurons in the thalamus and basal forebrain during cortical arousal.

Acetylcholine↗

Decrease in excitatory transmission within the lateral habenula and the mediodorsal thalamus protects against limbic seizures in rats.

We have used limbic convulsions induced by systemic pilocarpine in rats combined with focal intracerebral injections concurrently to study the initiation and spread of seizure activity. Protection against pilocarpine-seizure development by antagonism of excitatory or facilitation of inhibitory neurotransmission at focal sites establishes the anatomical circuits involved in the propagation of seizures. The excitatory amino acid antagonist 2-amino-7-phosphonoheptanoate (APH, selective for the NMDA preferring glutamate receptor subtype) is potently anticonvulsant after bilateral focal injections into the habenula or mediodorsal thalamus. The dose of APH required to give sustained protection against pilocarpine-induced convulsions is 10 pmol for lateral habenula and 50 pmol for mediodorsal thalamus. The GABA agonist muscimol produces a similar sustained protection following focal injections (100 pmol/side) into either the lateral habenula or the mediodorsal thalamus. An overall decrease in the efferent neurotransmission of these two brain regions results in a strong anticonvulsant effect indicating their importance in modulating limbic seizure activity.

2-Amino-5-phosphonovalerate↗

Median and tibial somatosensory evoked potentials. Changes in short- and long-latency components in patients with lesions of the thalamus and thalamo-cortical radiations.

Alterations in short- and long-latency components of median and tibial somatosensory evoked potentials (SEPs) were studied in patients with lesions in the thalamus and thalamo-cortical radiations. When the lesions were located primarily in the ventro-posterior thalamus, the SEP changes consisted of the following combination: absence of response; decrease in response amplitude; delay in peak latency; and attenuation of median N20-P25 and tibial P40. The laterally situated ventro-posterior lesions tended to preferentially affect tibial SEPs whereas the medially situated lesions tended to preferentially affect median SEPs. The lateral thalamic lesions affected primarily the long-latency SEP components, whereas the medial thalamic lesions affected primarily the mid-latency or the mid- and long-latency SEP components. Corona radiata infarcts produced SEP changes similar to those with the ventro-posterior thalamic lesions except that absence of evoked responses was not observed. Subcortical infarcts tended to affect the mid- and long-latency SEP components with relative preservation of the short-latency components. The present data indicate that only the lesions involving the primary thalamic relay area affected all SEP components, particularly the short-latency components, and that the lesions in other thalamic areas can also influence the SEPs, particularly the mid- and long-latency components. The present study further demonstrates that a combined use of median and tibial SEPs is useful in delineating the topographic organization of the somatosensory system in the thalamus.

Adult↗

Age associated decrements in dopamine D2 receptors in thalamus and in temporal insula of human subjects.

This study evaluates the effects of age on DA D2 receptors in extrastriatal regions. DA D2 receptor availability was evaluated in 42 healthy male subjects (mean age 41 +/- 16, range 21 - 86 year old) with positron emission tomography (PET) and [11C]raclopride. Estimates of Bmax/Kd were obtained using the ratio of the distribution volume in the region of interest (caudate, putamen, thalamus, frontal, occipital cortices, temporal insula, cingulate and orbitofrontal gyri) to that in cerebellum. Correlations between age and D2 receptors were significant in putamen (r = -0.58, p < or = 0.0001), caudate (r = -0.54, p < or = 0.0002), thalamus (r = -0.33, p < or = 0.03) and temporal insula (r = -0.39, p < or = 0.01) but not in any of the frontal regions. The decrease in DA D2 receptor availability was 6.6% per decade in caudate, 8.2% in putamen, 7.6% in thalamus and 13% in temporal insula. This study indicates that D2 losses with age are not limited to striatum and involve also thalamic as well as temporal cortical regions.

Adult↗

Modulation of sensory neurone excitatory and inhibitory responses in the ventrobasal thalamus by activation of metabotropic excitatory amino acid receptors.

Several different types of metabotropic excitatory amino acid receptors (mGluRs) are present in the thalamus. We have previously shown that the agonists L-AP4 and CCG-I can have apparently presynaptic effects on GABAergic inhibitory transmission in the thalamus. In this study we attempted to characterize the different receptor types which may mediate these effects and the known post-synaptic excitatory actions of 1S,3R-ACPD in the ventrobasal thalamus, by using a number of agonists with different spectra of activity at the various mGluRs. Inhibitory responses in ventrobasal thalamic neurones of urethane-anaesthetized rats were evoked by air-jet stimuli to the vibrissae and extracellular recording methods were used to reveal inhibitory responses as an inhibition of excitatory responses in a condition-test paradigm. The Group II and Group III mGluR agonists L-AP4, CCG-I, DCG-IV, 1S,3R-ACPD and S-4C3HPG, applied in the vicinity of the recording site by iontophoresis, were found to reduce inhibitions revealed by the condition-test paradigm (by 67, 75, 50, 43 and 77% from control inhibitions, respectively). The endogenous mGluR agonist L-serine-O-phosphate (L-SOP) was found to have similar, although weaker, actions (31% reduction of inhibition), while the Group I agonist 3,5-DHPG had little effect in this test (9% reduction of inhibition). In contrast, both 3,5-DHPG and 1S,3R-ACPD had direct excitatory actions on VB neurones, and these could be antagonized by 4CPG. The effects of CCG-I in the condition-test paradigm could be antagonized by the antagonists MCCG, MCPG, but not MAP4.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Distribution of tachykinin- and enkephalin-immunoreactive fibers in the human thalamus.

Sections at regular intervals through the human thalamus and alternating with those used for histochemical and cytoarchitectonic analysis in the companion paper, were stained immunocytochemically with a monoclonal antibody that recognizes tachykinins, including substance P, and with an antiserum against metenkephalin-arg-gly-leu (MERGL). Immunoreactivity for both types of molecule is found in fiber systems that enter the thalamus: (a) anteromedially, from the hypothalamus and prethalamic regions; (b) posterolaterally, from the midbrain tegmentum. No immunoreactive somata were observed in the thalamus. The chief nuclei in which dense, apparently terminal, ramifications of both sets of immunoreactive fibers are found include the posterior complex (Po, L and Sg), the intralaminar nuclei except the centre median, and a small nucleus tentatively identified as the nucleus submedius. It is significant that many of these nuclei have been implicated in pain phenomena, that most of them receive spinothalamic inputs, and that spinal cells at the origins of the tract are immunoreactive for substance P or metenkephalin. This study provides further evidence for the close similarity between nuclear delineation in the human and monkey thalami.

Aged↗

Regulation of regional blood flow in the laterodorsal thalamus by ascending cholinergic nerve fibers from the laterodorsal tegmental nucleus.

The laterodorsal tegmental nucleus (LDT) is the largest aggregation in the brainstem of cholinergic neurons whose axons reach the thalamus as part of a diffuse projection to the forebrain. We measured the regional blood flow in the thalamus by means of laser Doppler flowmetry, and examined whether the blood flow was regulated by the ascending cholinergic nerve fibers originating in the LDT. Experiments were performed on urethane-anesthetized rats whose upper cervical spinal cord was transected to avoid response of systemic blood pressure following LDT stimulation. The ascending cholinergic nerve fibers were excited by electrical or chemical stimulation applied to the LDT. The regional thalamic blood flow increased in response to repetitive electrical stimulation and chemical stimulation with L-glutamate to the LDT. The response, starting several seconds after the onset of electrical stimulation and lasting as long as 1 min, was reduced by i.v. scopolamine, a cholinergic muscarinic receptor antagonist. The results indicate that regional blood flow in the thalamus is increased by excitation of the ascending cholinergic nerve fibers originating in the LDT mainly through the cholinergic muscarinic receptors.

Afferent Pathways↗

Changes of single unit activity in the cat's auditory thalamus and cortex associated to different anesthetic conditions.

Single unit spike trains were recorded in the auditory cortex (n = 78) and in the auditory thalamus (n = 55) of nitrous oxide anesthetized cats. The electrophysiological activity was studied before and during the application of pentobarbital (P, 7 mg/kg), ketamine (K, 12 mg/kg) and a mixture of these anesthetics (KP). The units were characterized during the spontaneous and acoustically driven activity ('white' noise and pure tone bursts). For the majority of cortical (61%) and thalamic (83%) units both drugs tended to decrease the spontaneous firing rate, but affected differently its time structure: P tended to increase the average size of burst discharges, whereas K and KP tended to decrease it. In the cortex the peak firing rate evoked by 'white' noise tended to be decreased, whereas stronger excitatory responses were observed in the thalamus after injection of K or KP. The overall effect of the anesthetics during stimulation by pure tones was an increase in tonal selectivity due to a decrease in the response bandwidth. The response pattern to tones was also sometimes affected by the drugs. The direct evidence reported here for significant alterations of the discharge properties of auditory neurons in the thalamus and cortex resulting from low dose administration of K and/or P emphasizes difficulties in comparing data derived from experiments conducted in various conditions of anesthesia or in the awake state.

Acoustic Stimulation↗

Changes in somatosensory evoked potentials following an experimental focal ischaemic lesion in thalamus.

Experiments have been performed to produce localized thalamic ischaemia in baboons anaesthetised with alpha-chloralose. Somatosensory evoked potentials to median nerve stimulation were recorded in the medial lemniscus, VPL of thalamus and the primary somatosensory cortex. Local blood flow was also recorded by the hydrogen clearance technique in these regions. The early potential recorded in thalamus has been shown to be generated from 3 sources: (i) a positivity generated outside the VPL, (ii) local wavelets, most likely from synaptic activity close to the recording electrode, and (iii) a local overall negativity. The first of these potentials alone remains after thalamic ischaemia. It arises below the level of the thalamus, being very likely generated by the afferent volley in the medial lemniscus, and is seen in the surface-recorded response as the early component P8 (corresponding to P15 in the human).

Animals↗

Functions of ionotropic and metabotropic glutamate receptors in sensory transmission in the mammalian thalamus.

The thalamic relay nuclei play a pivotal role in gating and processing sensory information en route to the cerebral cortex. The major ascending sensory afferents and the descending cortico-fugal afferents to the thalamus almost certainly use the excitatory amino acid L-glutamate as their transmitter. This paper reviews the nature of this transmission in terms of the receptor types which may be used (NMDA, AMPA, kainate and metabotropic glutamate receptors), their electrophysiological and pharmacological properties, and their differential location in the thalamus on neurones, terminals and glial elements. Whilst AMPA receptors, probably of more than one variety, are likely to mediate fast transmission in the thalamus, the contributions of NMDA receptors and metabotropic glutamate receptors to sensory responses under different stimulus conditions may be more varied. This is discussed in the context of the possible functional significance of the interplay of L-glutamate-gated currents with intrinsic membrane currents of thalamic neurones. The interaction of L-glutamate transmission with other modulators (acetylcholine, noradrenaline, serotonin, glycine, D-serine, nitric oxide, arginine, redox agents) is considered.

Animals↗

Histamine H2-receptors participate in the formation of brain edema induced by kainic acid in rat thalamus.

At 4 h after the intraperitoneal administration of kainic acid in a dose of 12 mg/kg, Evans blue extravasation was observed preferentially in the thalamus, accompanied by increases in the water and sodium contents and by a decrease in the potassium content. Subcutaneous pretreatment with a histamine H2-receptor blocking agent, ranitidine, in a dose of 5 mg/kg given 2 h before and at the time of kainic acid injection, partially decreased the edema formation in the thalamus. It is assumed that repetitive discharges evoked by the kainic acid result in the thalamus in an excessive release of histamine from internal (mast cell and neuronal) sources and that this leads to the activation of H2-receptor-coupled adenylate cyclase in the brain microvessels and to the induction of brain edema.

Animals↗

Lack of GABAergic modulation of acetylcholine turnover in the rat thalamus.

In order to investigate the GABAergic modulation of the cholinergic midbrain-thalamus pathway, the effects of the GABAA agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) and of the benzodiazepine, diazepam, on acetylcholine (ACh) turnover in the thalamus have been studied. TRACh was also measured in the frontal and parietal cortices of the same animals. Our data confirm an inhibitory GABAergic modulation of the cholinergic nucleus basalis-cortex projection but suggest a lack of GABAergic modulation of the cholinergic midbrain-thalamus pathway.

Acetylcholine↗

Connections of the thalamic reticular nucleus with the contralateral thalamus in the rat.

The occurrence of thalamic projections to the contralateral side of the thalamus, and the origin of these projections from the thalamic reticular nucleus, were demonstrated with fluorescent retrograde tracing. After a relatively large tracer injection in the anterior third of the thalamus (involving the reticular, anterior, intralaminar and ventrolateral nuclei), labeled cells were detected in the rostral portion of the contralateral reticular nucleus. The location within the reticular nucleus of the neurons retrogradely labeled in the contralateral thalamus was confirmed by means of the combination of tracing with immunocytochemistry, using antibodies against the calcium binding protein parvalbumin.

Animals↗

MK-801 inhibits the induction of immediate early genes in cerebral cortex, thalamus, and hippocampus, but not in substantia nigra following middle cerebral artery occlusion.

Middle cerebral artery (MCA) occlusion in rats induced c-fos and junB mRNA 4h later in all ipsilateral cortex outside the MCA distribution and in many subcortical structures: medial striatum; most of thalamus including medial and lateral geniculate nuclei: substantia nigra; and hippocampus. The N-methyl-D-aspartate (NMDA) antagonist, MK-801 (4 mg/kg, i.p.) inhibited c-fos and junB mRNA induction in the cortex, striatum, thalamus, and hippocampus but not in the substantia nigra. These data show that c-fos and junB mRNA induction in cortex, striatum, thalamus, hippocampus involves the activation of NMDA receptors whereas different receptors must be implicated in the induction in substantia nigra.

Animals↗

Abnormal single-unit activity recorded in the somatosensory thalamus of a quadriplegic patient with central pain.

We have performed single unit analysis of the activity of cells located in the ventral nuclear group of thalamus in a patient with dysesthetic pain below the level of a clinically complete traumatic spinal cord transection at C5. Cells located in the parasagittal plane 14 mm lateral to the midline responded to tactile stimulation in small facial and intraoral receptive fields, which were characteristic of patients without somatosensory abnormality [30]. In this patient the 16 mm lateral parasagittal plane contained cells with receptive fields located on the occiput and neck instead of the upper extremity as would normally be expected. Cells with receptive fields on the neck and occiput had not previously been observed in recordings from single units (n = 531) responding to somatosensory stimulation [30]. Thus, on the basis of their location in a region of thalamus which normally represents parts of the body below the level of the spinal cord transection and their unusual receptive fields adjacent to these same parts of the body, we propose that the cells in the 16 mm lateral plane have lost their normal afferent input. Analysis of the autopower spectra of spike trains indicates that cells in the 16 mm lateral plane exhibited a higher mean firing rate and greater tendency to fire in bursts than cells in the 14 mm lateral plane (P less than 0.005). Finally, electrical stimulation at the recording sites in the 16 mm lateral plane evoked a burning sensation in the occiput, neck and upper extremity. These results suggest that regions of thalamus which have lost their normal somatosensory input contain neurons which exhibit abnormal spontaneous and evoked activity and that electrical stimulation of these regions can produce the sensation of burning dysesthesia.

Action Potentials↗

Nociceptive responses in medial thalamus of the normal and arthritic rat.

Recordings were obtained from 773 neurons located in the medial thalamus of rats. 23 of the 46 rats studied had been rendered arthritic by prior inoculation with Freund's adjuvant. 262 of the neurons could be activated by peripheral stimulation. In all cases but one, only stimuli considered to be nociceptive were effective in producing responses. Most of the responses were excitatory. The majority of the responsive neurons were located in the submedius (SM), mediodorsal (MD), centrolateral, paracentral, ventromedial (VM) nuclei and medial parts of the ventrolateral (VL) nucleus. A few nociceptive neurons were also recorded in anteromedial (AM), reuniens and a few other nearby regions of thalamus. Most neurons could be activated by stimuli applied bilaterally and frequently to large regions of the body. In almost all cases the responses were maintained for the entire duration of the 15 sec stimuli used and in some cases continued after cessation of the stimuli. No marked differences in incidence of responsive neurons were found between the normal and arthritic rats or between different regions. There were also no marked differences in the spontaneous rates, magnitudes of responses, or incidence of after-discharges of neurons in the various regions of medial thalamus. These findings indicate the existence of neurons responding to nociceptive stimuli in MD, AM, VM, and VL in addition to the intralaminar nuclei and SM and suggest that all these regions may be involved in mediating various aspects of nociception.

Action Potentials↗

Fastigial nucleus projections in the midbrain and thalamus in dogs.

Efferent connections to midbrain and thalamus from portions of the cerebellar fastigial nucleus were investigated using autoradiographic techniques. Bipolar stimulating electrodes were placed in the fastigial nucleus of anesthetized beagles and the area which produced maximal increases in blood pressure and heart rate was localized in each dog. A mixture of [3H]leucine and [3H]proline (4:1) was injected into that area and autoradiograms were prepared. Injections filled the rostral and various parts of the caudal fastigial nucleus. The rostral-caudal extent of injection sites were mapped in the horizontal plane from sequential coronal, thionin-stained sections and "primary" and "secondary" injection zones were defined according to specific criteria. Labeled axons reached the mesencephalon via the contralateral uncinate fasiculus. Ascending fibers assembled in a diffuse contingent at the prerubral level adjacent to the ventrolateral periaqueductal gray. The heaviest projections were contralateral to the injection site, but ipsilateral terminals were observed as well. In the midbrain, axons entered the contralateral and ipsilateral superior colliculus to branch repeatedly and terminate in the deep and intermediate layers. Additional terminals were observed bilaterally in the nuclei of the posterior commissure and pretectal areas at the midbrain-diencephalic junction. In the thalamus, labeled axons formed into three groups which terminated in: the contralateral paraventricular complex and medial dorsal nucleus; the contralateral central medial, paracentral, parafasicular and central lateral nuclei, and the contralateral ventral medial and ventral lateral nuclei. There was a sparse projection to the ipsilateral ventral lateral nucleus. The contralateral projection to the ventral medial and ventral lateral nuclei was marked by dense clusters of label ventral to the internal medullary lamina extending, in the dorsal ventral lateral nucleus, to its rostral pole. Projections to specific somesthetic thalamus or the hypothalamus were not observed. These ascending projections in the canine brain generally conform to those described in other nonprimate mammals. The fastigial nucleus presumably provides information concerning equilibrium and body proprioception to the superior colliculus and to thalamic nuclei including both specific motor relay and "nonspecific" midline and intralaminar nuclei, much the same as reported in the cat. The projection to the ventral medial and ventral lateral thalamic nuclei terminate in areas known to participate in the control of axial and proximal limb muscle activity.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗

Local circuit neurons in the rat ventrobasal thalamus--a GABA immunocytochemical study.

The ventrobasal thalamus of seven rats was processed for immunocytochemistry using antisera to glutamate decarboxylase or gamma-aminobutyrate (GABA). Glutamate decarboxylase-stained sections showed a network of stained fibers and terminals but no stained cell bodies. GABA-stained sections had fewer stained fibers and terminals but did show a few stained cell bodies. Cell bodies were especially apparent when carbazole was used for a chromogen for the peroxidase-antiperoxidase visualization. The GABA-stained cells were found to be distributed throughout the ventrobasal complex, to have smaller soma cross-sectional areas than most other cells (81 +/- 34 microns vs 105 +/- 36 microns for all cells) and to make up 0.4 +/- 0.3% of the neuronal population of the ventrobasal complex. Injections of horseradish peroxidase into the somatosensory cortex (SI) retrogradely filled many neurons in the ventrobasal thalamus, but none of these labeled neurons were double labeled with GABA. These results indicate that the GABA-labeled cells probably represent a small population of local circuit neurons in the rat ventrobasal thalamus.

Animals↗