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Impairment of radial maze delayed nonmatching after lesions of anterior thalamus and parahippocampal cortex.

This study compared the effects of lesions damaging hippocampus-related pathways in anterior thalamus (AT) and parahippocampal (PH) cortex on allocentric spatial memory. Rats were trained to perform radial maze delayed nonmatching (DNM) with random selection of arms to prevent egocentric solutions. After experimental treatment (control, excitotoxic AT, radiofrequency PH, or combined AT-PH lesions), rats were retrained for 30 sessions from 2 to 8 weeks after surgery. Results showed comparable impairments for AT and PH lesions that added without interaction in the combined AT-PH group. During chronic recovery, the AT-PH group exhibited delay-dependent deficits comparable to previous results for hippocampal lesions. Thus, AT and PH lesions appear to have separate effects that together disrupt hippocampus-dependent spatial memory.

Animals↗

Paired-spike interactions and synaptic efficacy of retinal inputs to the thalamus.

In many neural systems studied in vitro, the timing of afferent impulses affects the strength of postsynaptic potentials. The influence of afferent timing on postsynaptic firing in vivo has received less attention. Here we study the importance of afferent spike timing in vivo by recording simultaneously from ganglion cells in the retina and their targets in the lateral geniculate nucleus of the thalamus. When two spikes from a single ganglion-cell axon arrive within 30 milliseconds of each other, the second spike is much more likely than the first to produce a geniculate spike, an effect we call paired-spike enhancement. Furthermore, simultaneous recordings from a ganglion cell and two thalamic targets indicate that paired-spike enhancement increases the frequency of synchronous thalamic activity. We propose that information encoded in the high firing rate of an individual retinal ganglion cell becomes distributed among several geniculate neurons that fire synchronously. Because synchronous geniculate action potentials are highly effective in driving cortical neurons, it is likely that information encoded by this strategy is transmitted to the next level of processing.

Action Potentials↗

Induction of c-fos, junB, c-jun, and hsp70 mRNA in cortex, thalamus, basal ganglia, and hippocampus following middle cerebral artery occlusion.

Middle cerebral artery (MCA) occlusion in halothane-anesthetized rats induced c-fos, junB, and c-jun immediate early gene mRNAs and hsp70 heat shock gene mRNA in brain. In situ hybridization studies showed that c-fos and junB were induced throughout all of the cortex at 1 and 4 h following MCA occlusion. hsp70 was induced in the core and margins of the MCA ischemia. By 24 h, there was little expression of c-fos, junB, c-jun, and hsp70 in the core of the MCA infarct; there was modest induction of hsp70 at the margins of the infarct; and there was diffuse induction of c-fos, junB, and c-jun in all of the cortex outside the infarct. MCA occlusion also induced these genes in subcortical structures. c-fos, junB, and hsp70 were induced in ipsilateral medial striatum, most of thalamus including medial and lateral geniculate nuclei, substantia nigra, and hippocampus. Most of these structures, except for the striatum, are not supplied by the MCA. These data show that changes in gene expression can occur in regions remote from an infarction.

Animals↗

Lesions of the posterior paraventricular thalamus block habituation of hypothalamic-pituitary-adrenal responses to repeated restraint.

We examined the role of the posterior division of the paraventricular nucleus of the thalamus (pPVTh) in habituation of hypothalamic-pituitary-adrenal (HPA) responses to repeated restraint. Habituation refers to the decrement in HPA activity that occurs with repeated exposure to the same or homotypic stressor. To date, the pPVTh has been shown to inhibit the enhanced or facilitated HPA responses to novel, heterotypic restraint in previously chronically cold stressed rats. We hypothesized that the pPVTh also inhibits HPA activity under conditions of habituation. In the first experiment, we lesioned the pPVTh and examined adrenocorticotropic hormone (ACTH) and corticosterone responses to the first or eighth restraint exposure. In sham-lesioned rats, we found lower ACTH and corticosterone responses to the eighth period of 30 min restraint compared to the first exposure, evidence for habituation. In pPVTh-lesioned rats, there was no difference in ACTH and corticosterone responses to the eighth compared to the first restraint exposure. Therefore, pPVTh lesions prevented the habituation of HPA responses to repeated restraint. In the second experiment, we examined whether habituation to restraint is observable in response to an acute, single restraint on day 28 in sham and pPVTh lesioned rats that were exposed to restraint only on days 1 through 8. In this experiment, we replicated the results from the first experiment, and found evidence that habituation to restraint can be observed weeks after chronic stress has been terminated. Furthermore, pPVTh lesions had no additional effects on HPA responses to acute stress on day 28. In summary, pPVTh lesions inhibit habituation of HPA activity to a homotypic stressor, without altering HPA responses to the first restraint. Thus, the intact pPVTh inhibits HPA activity under conditions of habituation, as well as facilitation, and represents an important regulator of HPA activity under conditions of chronic stress.

Acute Disease↗

Striatal projections from the cat visual thalamus.

Anterograde transport methods reveal an extensive thalamostriate projection from the extrageniculate visual thalamus. These projections distribute to approximately the same regions of the striatum innervated by the corticostriate projections from over a dozen higher visual cortical areas [visual-recipient sector; Updyke, B.V. (1993) J. Comp. Neurol., 327, 159-193.]. Like their cortical counterparts, the thalamostriate projections to the caudate distribute in a patchy manner that suggests potential overlap or intermingling spatial relationships between the two major afferents. All of the visually related thalamic nuclei projecting to the striatum receive ascending signals from the superior colliculus, suggesting that the constraints placed upon tectal processing by striatonigral control have important consequences for central perceptuomotor processing at the striatal and cortical levels.

Animals↗

Habituation and cross-sensitization of stress-induced hypothalamic-pituitary-adrenal activity: effect of lesions in the paraventricular nucleus of the thalamus or bed nuclei of the stria terminalis.

Habituation of the hypothalamic-pituitary-adrenal (HPA) response to chronic intermittent restraint stress (30 min/day for 15 days) and the cross-sensitization to a heterotypic stress [i.p. lipopolysaccharide (LPS)] were investigated in intact male Sprague Dawley rats, and in rats bearing quinolinic acid lesions to the medial anterior bed nuclei of the stria terminalis (BST) or anterior region of the paraventricular nucleus of the thalamus (PVT). In intact animals, a single period of restraint increased plasma corticosterone levels at 30 min and led to an increase in corticotropin-releasing hormone (CRH) mRNA levels in the PVN at 3 h. LPS had a smaller effect on corticosterone and more variable effect on CRH mRNA. Chronic intermittent restraint stress caused a decrease in body weight and increase in adrenal weights, with concomitant increase in basal corticosterone levels. These animals also displayed marked habituation of the corticosterone and CRH mRNA responses to the homotypic stress of restraint, but no loss of the corticosterone response to the heterotypic stress of LPS and a cross-sensitization of the CRH mRNA response. This pattern of stress responses in control and chronically stressed animals was not significantly affected by lesions to the PVT or BST, two areas which have been implicated in the coping response to stress. Thus, these data provide evidence for independent adaptive mechanisms regulating HPA responses to psychological and immune stressors, but suggest that neither the medial anterior BST nor the anterior PVT participate in the mechanisms of habituation or cross-sensitization.

Animals↗

Neural substrates of microstimulation-evoked tingling: a chronaxie study in human somatosensory thalamus.

Intra-operative micro-electrode stimulation of sensorimotor thalamus produces paraesthesia or tingling in various body regions and is used to map somatotopy prior to implantation of deep brain-stimulating electrodes in awake patients. The neural elements affected by such microstimulation are unknown. Using paraesthesia as the behavioural-physiological response threshold, we measured chronaxie times for microstimuli applied to both somatosensory thalamic nuclei (cellular region) and its axonal afferents, the medial lemniscus. White matter chronaxie times were relatively unimodal, whereas two different clusters of chronaxie times were identified in grey matter: one corresponding to that of the medial lemniscus and the other about five times longer and compatible with that obtained from cell somata. Therefore, excitations of local axons and/or cell bodies can both contribute to the paraesthesia evoked during intra-operative thalamic mapping.

Brain Mapping↗

Cerebellar connections to the rostral reticular nucleus of the thalamus in the rat.

We studied the cerebellar connections to the reticular nucleus thalamus (RNT) by means of retrograde axonal transport of horseradish peroxidase (HRP) in the rat. Specific HRP pressure injections to the rostral RNT (1.6-1.8 mm caudal to bregma) resulted in retrograde labelling of neurones in the cerebellar nuclei. The rostral RNT showed specific topographical organization of its cerebellar connections. Microinjections into the rostral RNT, 1.6 mm caudal to bregma, produced numerous HRP-labelled neurones within the anterior interposed (emboliform nucleus) and scarce HRP-labelled neurones within the lateral (dentate nucleus) cerebellar nuclei, whereas injections into the rostral RNT, 1.8 mm caudal to bregma, produced numerous HRP-labelled neurones within the posterior interposed (globose nucleus) and scarce lightly HRP-labelled neurones within the lateral (dentate nucleus) cerebellar nuclei. Cerebellar connections with the rostral RNT were exclusively ipsilateral to the injection site. No HRP-labelled cells were detected in the medial (fastigial nucleus) cerebellar nucleus. The cerebellar connections reach the RNT via the superior cerebellar peduncle. By contrast, HRP injections into the anterior, posterior interposed and lateral cerebellar nuclei produced no labelled cells within the RNT. This study demonstrates the existence of direct cerebello-RNT but not RNT-cerebellar connections. The presence of the cerebello-RNT connections introduces a new route through which the cerebellum may influence RNT and thus cerebral cortical activity.

Animals↗

Dynamic changes of status epilepticus-induced neuronal degeneration in the mediodorsal nucleus of the thalamus during postnatal development of the rat.

PURPOSE: Status epilepticus (SE) was previously found to induce damage in the mediodorsal nucleus of the thalamus (MD) in both adult and immature rats. This study was designed to describe age-related changes of SE-induced neuronal degeneration in this part of the brain. METHODS: SE was induced by LiCl/pilocarpine in five age groups of rats (P12-P25). Distribution of degenerating neurons was studied at various time intervals from 4 h up to 1 week using Fluoro Jade B (FJB) staining. For P12 and P25 rats, an interval of 3 months was added. RESULTS: Damaged neurons were found in all age groups during a 1-week period after SE. Patterns of neuronal degeneration, however, changed in an age-related manner. In animals at P12 and P15, FJB-labeled neurons were located in the central and lateral segment of the MD. In the P18 group, degenerating neurons occurred in all three segments of the MD, with a prevalence in central and lateral subdivisions. In contrast, in P21 and P25 rats, FJB-labeled neurons were predominantly located in the central and medial segments. Degenerating neurons were still present 3 months after SE in the medial segment in P25 animals, whereas no labeled neurons were detected in the P12 group at this time. CONCLUSIONS: Our data demonstrate that the pattern of neuronal degeneration in MD is mainly related to age at SE onset. In addition to damage occurring during the acute phase of SE, a population of degenerating neurons was detected in P25 animals during the chronic period 3 months after SE.

Aging↗

Immediate reorganization of the rat somatosensory thalamus after partial ligation of sciatic nerve.

Nerve injury can result in neuropathic pain, which persists after the injury and may occur after healing is completed. The long-term central reorganization associated with neuropathic pain has been previously studied in animal models. The immediate effects of nerve injury on central representation, however, are poorly understood. We examined the population response properties of closely neighboring neurons located in the hindlimb representation area of the somatosensory thalamus. Changes in the neuronal population properties were characterized before, during, and after (up to 6 hours) partial ligation of the sciatic nerve in the rat. Changes in these properties were observed within minutes after nerve injury. There were changes in neuronal class and receptive field size, emergence of new receptive fields, receptive fields observed before ligation disappeared temporarily after ligation, and changes in number of spikes evoked by the same stimulus. The rates of these changes in central representation were essentially zero before ligation, maximal within minutes after ligation, and decreased to a steady sustained rate of change within 1 to 2 hours. The incidence of functional connectivity, as measured by cross-correlations, remained unchanged. However, the strength of functional connectivity increased after ligation. The results show immediate reorganization of lateral thalamic networks with peripheral nerve damage. When the population response is considered as the underlying code, this reorganization does not reflect the behavioral manifestations of hyperalgesia and allodynia, even though some of the individual neuronal responses do reflect properties consistent with the hyperalgesia and allodynia reported within the same time frame after nerve injury in the rat.

Journal Article↗

Morphine acute effects on spontaneous multiunit activity recorded simultaneously from medial thalamus and caudate nucleus in freely behaving rats.

Treatment with varying doses of morphine and its antagonist naloxone produced different response patterns in "spontaneous" multiunit discharges recorded from the medial thalamus and caudate nucleus of freely behaving rats previously implanted, stereotaxically, with permanent semimicro-electrodes. The changes in electrical discharges induced by incremental doses of morphine exhibited dose-related patterns, and could be reversed by naloxone. This procedure, testing several incremental doses of a drug, provides a tool with which to identify and classify the specific response patterns induced by morphine. The two structures examined in the present study exhibited four response patterns to the treatments but only one pattern of response was similar in the two nuclei. The medial thalamic units are more sensitive to morphine than those recorded from the caudate nucleus. The present finding, i.e., acute effects of morphine, provides basic information with which to examine the physiological properties underlying the chronic effects of morphine.

Animals↗

The effects of clonidine and tizanidine on responses of nociceptive neurons in nucleus ventralis posterolateralis of the cat thalamus.

The effects of intravenous clonidine and tizanidine on nociceptive neurons in the nucleus ventralis posterolateralis (VPL) of the thalamus, a key station in the lateral system of ascending pain pathways, were evaluated in urethane-chloralose anesthetized cats. Intravenous clonidine and tizanidine produced a dose-dependent (5 and 10 micrograms/kg, and 25 and 50 micrograms/kg, respectively) suppression of responses of nociceptive specific (NS) and wide dynamic range (WDR) neurons in the VPL to high threshold splanchnic input. In contrast, the responses of both NS and WDR units to electrical stimulation of spinothalamic tract fibers in the ventrolateral funiculus (VLF) were little affected. We conclude that a site of suppressive action of the alpha 2-adrenoceptor agonists, as observed in nociceptive VPL neurons, is at the level of the spinal dorsal horn rather than in the VPL itself.

Adrenergic alpha-Agonists↗

Thalamus and neurogenic pain: physiological, anatomical and clinical data.

Microelectrode recordings in the medial thalamus of 45 neurogenic pain patients undergoing medial thalamotomy revealed that most units (316/318) did not respond to somatosensory stimuli, and that half exhibited low-threshold calcium spike bursts. After medial thalamotomy, 67% of the patients reached a 50 to 100% pain relief, without somatosensory deficits. Colocalization of bursting activities and of the most efficient therapeutic lesions in the central lateral nucleus suggests a key role of this structure in neurogenic pain. We propose that neurogenic pain is due to an imbalance between central lateral and ventroposterior nuclei, resulting in an overinhibition of both by the thalamic reticular nucleus.

Follow-Up Studies↗

Muscarinic M1 and M2 receptor subtype selective drugs modulate neocortical EEG via thalamus.

The present study was designed to investigate the effects of infusions into reticular nucleus of thalamus (NRT) or intracerebroventricular (i.c.v.) infusions of muscarinic M1 and M2 receptor subtype selective drugs on thalamocortically generated neocortical high voltage spindles (HVSs) in awake immobile rats. NRT administration of 2.0 and 20.0 microg McN-A-343, a muscarinic M1 agonist, and 20.0 microg methoctramine, a muscarinic M2 antagonist, suppressed HVSs. The results suggest that the blockade of presynaptic M2 receptors and activation of postsynaptic M1 receptors in the NRT suppress thalamocortical oscillations and increase neocortical electrical arousal.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗

Stroke involving the midbrain and thalamus and causing 'nonfocal' coma.

We have described two patients who had coma without focal findings and who were found to have an ischemic stroke involving the midbrain and the thalamus. In both cases metabolic encephalopathy or drug overdose was initially suspected, but recognition of abnormal vertical eye movements led to the proper diagnosis. Examination of vertical eye movements in drowsy or comatose patients may be helpful in arriving at the correct diagnosis early and may prevent unnecessary investigations.

Cerebral Infarction↗

Evidence for a role of the parafascicular nucleus of the thalamus in the control of epileptic seizures by the superior colliculus.

PURPOSE: The aim of this study was to investigate whether the nucleus parafascicularis (Pf) of the thalamus could be a relay of the control of epileptic seizures by the superior colliculus (SC). The Pf is one of the main ascending projections of the SC, the disinhibition of which has been shown to suppress seizures in different animal models and has been proposed as the main relay of the nigral control of epilepsy. METHODS: Rats with genetic absence seizures (generalized absence epilepsy rat from Strasbourg or GAERS) were used in this study. The effect of bilateral microinjection of picrotoxin, a gamma-aminobutyric acid (GABA) antagonist, in the SC on the glutamate and GABA extracellular concentration within the Pf was first investigated by using microdialysis. In a second experiment, the effect of direct activation of Pf neurons on the occurrence of absence seizures was examined with microinjection of low doses of kainate, a glutamate agonist. RESULTS: Bilateral injection of picrotoxin (33 pmol/side) in the SC suppressed spike-and-wave discharges for 20 min. This treatment resulted in an increase of glutamate but not GABA levels in the Pf during the same time course. Bilateral injection of kainate (35 pmol/side) into the Pf significantly suppressed spike-and-wave discharges for 20 min, whereas such injections were without effects when at least one site was located outside the Pf. CONCLUSIONS: These data suggest that glutamatergic projections to the Pf could be involved in the control of seizures by the SC. Disinhibition of these neurons could lead to seizure suppression and may be involved in the nigral control of epilepsy.

Animals↗

The Organization of Projections from Subdivisions of the Auditory Cortex and Thalamus to the Auditory Sector of the Thalamic Reticular Nucleus in Galago.

Anterograde and retrograde transport techniques were used to study the connexions between different subdivisions of the auditory cortex and thalamus with the thalamic reticular nucleus in the prosimian, Galago. In particular, the goal was to determine whether the primary auditory nucleus, GMv, and its cortical target, area I of the auditory cortex (A I), project to a different region of the auditory sector of the reticular nucleus from the secondary auditory nuclei, GMmc and Po and their cortical targets outside A I. The results show that the projections to and from the auditory sector are indeed segregated: injections of wheatgerm agglutinin-conjugated horseradish peroxidase into either GMmc or Po labelled cells and terminals along the medial, lateral and ventral borders of the auditory sector, forming a U-shaped pattern. Projections from area II of the auditory cortex produced almost an identical pattern of the terminal labelling in the auditory sector. In contrast, injections into GMv-labelled cells and terminals in the centre region of the auditory sector, in the 'interior' of the U-shaped region. Projections from A I were distributed to both the U-shaped border region and the central core of the auditory sector probably because A I received projections from GMmc, Po and GMv. The significance of these results depends on a comparison between the auditory and visual sectors of the reticular nucleus. Both sectors are divided into tiers or subsectors-one related to the primary relay nucleus, i.e. GLd or GMv, and the other related to the secondary relay nuclei, i.e. pulvinar nucleus, GMmc, Po, etc.

Journal Article↗

Simultaneous Demonstration of Serotonin-immunoreactive Terminals and GABAergic Neurons in the VPL Nucleus of the Cat Thalamus.

Pre-embedding immunoperoxidase (for serotonin) and postembedding immunogold (for gamma-aminobutyric acid; GABA) labelling were combined at light and electron microscopic levels to demonstrate the neuronal targets of serotonin (5-HT) afferents in the ventral posterior lateral nucleus (VPL) of the cat thalamus. 5-HT-immunoreactive fibres and terminal varicosities were found in close proximity to GABA-immunoreactive interneurons and non-GABAergic relay neurons. Ultrastructurally, the vast majority of 5-HT terminals made close membrane contacts without overt membrane specializations with GABAergic axon terminals, GABAergic presynaptic dendrites and GABAergic somata. A very small number of 5-HT terminals formed typical asymmetrical synapses with GABAergic presynaptic dendrites and with dendritic shafts of relay cells. Some 5-HT terminals participated with the presynaptic dendrites in triadic synaptic arrangements. These findings suggest a dual innervation pattern by 5-HT afferents in VPL and the release of 5-HT in large part at sites not associated with morphologically detectable synapses.

Journal Article↗