Centrum Medianum-parafascicular Complex Research Articles

Participation of the thalamic CM-Pf complex in movement performance in patients with dystonia.

The centrum medianum- parafascicular complex of the human thalamus has a critical influence on cortical activity and significantly influences somatosensory function, arousal, and attention. In addition to its cortical connections, this region of the intralaminar thalamic nuclei is also connected to motor areas of the basal ganglia and the brain stem. The goal of this study was to identify movement-related neurons in the centrum medianum-parafascicular complex and analyze the changes in their activity during voluntary movements in patients with cervical dystonia. Single-unit activity was recorded during the micro-electrode-guided surgical ablation procedures in patients with cervical dystonia. The neural responses and synchronous electromyographic signals of the neck and finger flexor muscles were simultaneously recorded. We found the following 3 types of movement-sensitive neurons in the centrum medianum-parafascicular complex: neurons that responded selectively to voluntary hand movement (hand-only neurons), neurons that selectively responded to neck movements (neck-only neurons), neurons responding to both hand and neck movements (combined neurons). We discovered the following 3 patterns of movement-related changes in neural activity: an increase in the firing rate, a reduction in the bursting activity, and short-term oscillations and synchronization with neighboring neurons. The most pronounced and prolonged responses were observed during movements involving neck muscles as well as during involuntary dystonic movements. The centrum medianum-parafascicular complex of the thalamus is a component of the subcortical network that participates in motor behavior and may be involved in the pathophysiology of cervical dystonia. © 2016 International Parkinson and Movement Disorder Society.

Empirically derived model of the role of sleep in associative learning and recuperative processes

Neuronal firing patterns, defined as intraburst temporal relations between sequential spike intervals, were monitored extracellularly from the rostral part of the nucleus reticularis (NR) and from the centrum medianum—parafascicular complex (CM-Pf) of the thalamus in adult freely moving cats during acquisition of bar pressing behavior (BP1) for milk reward, subsequent slow wave sleep (SWS1), and contiguous rapid eye movement (REM1) sleep, and then, 16 to 48 h later, after the animal fully learned the conditioned BP behavior (BP2). The patterns were defined on the basis of relative relations between sequential spike intervals. The intervals were compared in sequential pairs, moving one interval at a time. This method, if applied to random and/or independent values, generates a novel and well-defined theoretical distribution of inequality patterns which is uniquely sensitive to the history of spike train and plastic changes at neuronal membrane. The “information” encoded in single neuronal firing patterns was quantified using two criteria: (a) the magnitude of pattern emissions with reference to the random model; and (b) the difference between pattern distribution during BP1-training/acquisition and after the animal fully acquired the BP behavior. The latter patterns, termed BP2-template, were assumed to be composed only of patterns relevant for learned behavior. Thus, other patterns observed during BP-1, SWS, and REM were classified as spurious. During BP-1 training/acquisition of conditioned behavior, in 28 out of 265 neurons studied, the firing patterns linked to and relevant for BP behavior emerged in background of spurious patterns. Subsequently, during SWS-1, the relevant patterns were selectively suppressed below chance level. Conversely, during REM-1 sleep, contiguous with SWS-1, patterns linked to acquisition of BP behavior were strongly amplified above the level observed during BP1-training episode, while the ‘spurious’ patterns were eliminated. Thus, REM-1 patterns may be regarded as amplified precursors of the BP2-template which, 16 to 48 h later, and often after additional training, emerged with the acquired conditioned BP behavior. With reference to the random model, the emission magnitudes of individual BP-1 patterns were correlated with suppressions of same patterns during subsequent SWS-1. The magnitudes of these deficits were, in turn, correlated with subsequent REM1-induced amplified emission of same patterns. These observations indicate that: (a) acquisition of operantly conditioned behavior is linked to inversions in statistical distribution of patterns during BP1, SWS1, and REM1 episodes; and (b) the inversions are not random but graded, and therefore are likely to reflect the well-known graded nature of receptor desensitization which may result from repetitive exposure to neurotransmitters and/or modulators during a motor task that requires repetitive use of the same set of neuronal assemblies and pathways over a significant period of time. The neuronal firing patterns in “control” episodes of milk drinking from a bowl (BOWL) had, on the average, no significant relationships to BP, SWS, nor REM episodes. The results provide: (a) a novel insight into the information processing based on intraburst temporal organization of spike trains, as opposed to the mean firing rate; (b) a novel concept of homeostatic behavior of neurons which is consistent with current views on the physico-chemical dynamics of neuronal membrane and its receptors; (c) the first quantifiable empirical evidence for the relationships between firing patterns, learning, SWS, and REM sleep; and (d) the results suggest a new model for learning linked to recuperative role of sleep which is based on spatio-temporal inversion of neuronal interactions and depolarization-induced recovery (DIR) of synaptic receptors that had been down regulated during waking state. This notion is compatible with receptor changes in vitro and in vivo.

Cholinergic innervation of canine thalamostriatal projection neurons: An ultrastructural study combining choline acetyltransferase immunocytochemistry and WGA‐HRP retrograde labeling

Choline acetyltransferase (ChAT) immunocytochemistry and lectin-conjugated horseradish peroxidase (WGA-HRP) histochemistry were combined at the electron microscopic level to examine the morphology of cholinergic terminals in the canine centrum medianum-parafascicular complex (CM-Pf) and to localize cholinergic terminals making synaptic contact with retrogradely labeled CM-Pf thalamostriatal projection neurons. Following WGA-HRP injections into the caudate nucleus, CM-Pf neurons were heavily labeled with WGA-HRP reaction product. Examination with the electron microscope revealed retrogradely labeled neurons characterized by a large nucleus with deep infoldings of the nuclear envelope. ChAT-positive terminals were observed arising from small-diameter nonmyelinated axonal profiles. These terminals varied in size from 0.5 to 1.4 micron in long diameter. The smaller terminals (0.5-0.7 micron) were seen most frequently and established symmetrical or slightly asymmetrical synaptic contacts with small dendritic profiles. The larger ChAT-positive terminals (1.0-1.4 micron) were less frequently observed, contained several mitochondria and small clusters of pleomorphic vesicles, and contacted large dendritic shafts and cell somata. Some of the postsynaptic targets of both smaller and larger ChAT-positive terminals were identified as belonging to retrogradely HRP-labeled thalamostriatal neurons. These observations indicate that at least some thalamostriatal neurons within the CM-Pf complex are innervated by cholinergic terminals which probably arise from ChAT-positive cell bodies located within the pontomesencephalic tegmentum, particularly within the nucleus tegmenti pedunculopontinus and the laterodorsal tegmental nucleus. These findings provide evidence for direct influence by cholinergic brainstem nuclei over activities of thalamostriatal neurons.

Projections of brainstem core cholinergic and non-cholinergic neurons of cat to intralaminar and reticular thalamic nuclei

We combined the retrograde transport of wheat germ agglutinin conjugated with horseradish peroxidase with choline acetyltransferase immunohistochemistry to study the projections of cholinergic and non-cholinergic neurons of the upper brainstem core to rostral and caudal intralaminar thalamic nuclei, reticular thalamic complex and zona incerta in the cat. After wheat germ agglutinin horseradish peroxidase injections in the rostral pole of the reticular thalamic nucleus, the distribution and amount of retrogradely labeled brainstem neurons were similar to those found after tracer injection in thalamic relay nuclei (see preceding paper42). After wheat germ agglutinin horseradish peroxidase injections in the caudal intralaminar centrum medianum parafascicular complex, rostral intralaminar central lateral paracentral wing, and zona incerta, the numbers of retrogradely labeled brainstem neurons were more than three times higher than those found after injections in thalamic relay nuclei. The larger numbers of horseradish peroxidase-positive brainstem reticular neurons after tracer injections in intralaminar or zona incerta injections results from a more substantial proportion of labeled neurons in the central tegmental field at rostral midbrain (perirubral) levels and in the ventromedial part of the pontine reticular formation, ipsi- and contralaterally to the injection site. Of all retrogradely labeled neurons in the caudal midbrain core at the level of the cholinergic peribrachial area and laterodorsal tegmental nucleus. 45ȁ50% were also choline acetyltransferase-positive alter the injections into central lateral paracentral and reticular nuclei, while only 25% were also choline acetyltransferase-positive after the injection into the centrum medianum parafascicular complex.These findings are discussed in the light of physiological evidence of brainstem cholinergic mechanisms involved in the blockade of synchronized oscillations and in activation processes of thalamocortical systems.

Differential control of hypothalamically elicited flight behavior by the midbrain periaqueductal gray in the cat

The purpose of the present study was to determine the role of the midbrain periaqueductal gray (PAG) and thalamic centrum medianum-parafascicular complex (CM-Pf) in the regulation of hypothalamically elicited flight behavior in the cat. The experimental paradigm involved a comparison of the differences in response latencies between single stimulation of the hypothalamus and concurrent stimulation of the hypothalamus and sites in the PAG or the CM-Pf. Dual stimulation of the ventral and dorsal aspects of the PAG resulted in differential modulation of flight behavior. Stimulation of the dorsal PAG suppressed hypothalamically elicited flight behavior while stimulation of the ventral aspects of the PAG facilitated flight behavior. Facilitation of flight behavior was also found from stimulation of ventral portions of the CM-Pf.

Neural pathways mediating hypothalamically elicited flight behavior in the cat

This study has sought to identify hypothalamic pathways mediating flight behavior in the cat. Flight behavior, characterized by an initial pupillary dilatation and followed by vigorous attempts to leap out of the observation chamber, was elicited primarily by electrical stimulation of the medial preoptic region and dorsomedial hypothalamus, and to a lesser extent from the perifornical region. A [ 14C]-2-deoxyglucose analysis was utilized to examine brain regions functionally activated by stimulation of hypothalamic sites which elicited flight behavior. In a second series of experiments, [ 3H]leucine injected into regions surrounding electrode tips from which flight had previously been elicited, permitted identification of pathways arising from such functionally characterized sites. We describe for the first time pathways arising from the hypothalamus which mediate flight behavior. In spite of individual variation in placement of electrodes eliciting flight, a consistent pattern of labeling was observed following injection of either [ 14C]-2-deoxyglucose systemically or [ 3H]amino acids into the hypothalamus. The primary rostal target structures receiving inputs from flight electrode sites included the nuclei of the diagonal band, bed nucleus of the stria terminalis, medial amygdaloid nucleus, lateral septal nucleus, and anterior medial preoptico-hypothalamus. Caudal to the level of stimulation, the principal target nuclei involved the centrum medianum-parafascicular complex and the midbrain central gray substance. Possible roles of these nuclear regions in organization and regulation of flight behavior is discussed.

GABA in the intralaminar thalamic nuclei modulates dopamine release from the two dopaminergic nigro-striatal pathways in the Cat

Halothane-anaesthetized cats implanted with several push-pull cannulae were used to study the effects of the unilateral application of GABA (10 −5 M, 30 min) into thalamic intralaminar nuclei on the in vivo release of ( 3H)-dopamine (( 3H)-DA) newly synthesized from ( 3H)-tyrosine in both caudate nuclei (CN) and substantiae nigrae (SN). GABA applied into the left centralis lateralis nucleus (CL) elicited symmetric changes in the two CN, ( 3H)-DA release being initially reduced and thereafter markedly increased. On the contrary, an asymmetric pattern of responses was observed in the two CN during and after GABA application into the left centrum medianum parafascicular complex (CM/PF) since ( 3H)-DA release was decreased ipsilaterally and enhanced contralaterally. Changes in ( 3H)-DA release intervening in the two SN appeared to be triggered by processes independant from those operating in the CN. Hence, an immediate increase in ( 3H)-DA release with a time course distinct from that observed in other structures occurred in the contralateral SN after the application of GABA either into the left CL or the left CM/Pf. Furthermore in both cases, a biphasic response (decrease followed by an increase) similar to that intervening in the CN following GABA application into the CL was seen in the ipsilateral SN. Autoradiographic studies performed with ( 14C)-GABA (10 −5 M) revealed that the amino-acid did not spread out from the site of application. During and after GABA application (10 −5 M, 30 min) into the CL or the CM/Pf neuronal firing was markedly enhanced not only locally but also into respective contralateral homologous structures. These results further confirm the important and specific roles of distinct thalamic nuclei in the bilateral regulation of DA release from dendrites and nerve terminals of the nigro-striatal dopaminergic neurons.

Phasic loss of constraints in timing of neuronal spikes in the feline centrum medianum during EEG alpha-like activity

In unrestrained cats, temporal patterns of single neuronal firing in the centrum medianum-parafascicular complex (CM-Pf) of thalamus were studied during a state of motionless quiet wakefulness. The spike trains from each neuron were electronically divided into episodes that occurred during desynchronized EEG and those that occurred during bursts of 6–14 Hz EEG spindles or alpha-like activity over the parieto-occipital cortex and in the CM-Pf. Contrary to expectations based on the theory of inhibitory phasing of neuronal activity, the episodes of synchronized quiet wakefulness (S-QW) were associated with independent and random distribution of spike intervals, although they tended to occur in clusters. During episodes of desynchronized quiet wakefulness (D-QW), significant temporal patterns were emitted by most neurons studied. The results suggest that: (a) during D-QW and increased levels of vigilance, temporal patterns are generated by cognitive processes and enhanced specific connectivities between CM-Pf neurons and other systems; (b) if connectivity is defined as increased certainty of synaptic transmission and iterative activation of the same pathways, then the assumption that the gross EEG thalamo-cortical synchronization represents increased connectivities between the CM-Pf neurons and other systems, may be erroneous; and (c) since temporal patterns of single neuronal discharges are determined by specific spatio-temporal distribution of synaptic drive, therefore during EEG spindles, most EPSP-IPSP sequences impinging upon CM-Pf neurons are conveyed by randomly varying polysynaptic pathways and have random spatio-temporal distribution on the soma and dendrites. In light of other observations, such a process is equivalent to an active introduction of uncertainty or ‘entropy’ into the information processing system, a state which may be important in preserving plasticity of operational modes of CM-Pf neurons and those with which they directly and/or indirectly interact.

Behavioral alterations and loss of caudate modulation in the centrum medianum-parafascicular complex of the cat following electrolytic lesions of the substantia nigra

Extracellular activity in the centrum medianum-parafascicular complex was examined following electrolytic lesions of the substantia nigra in the cat. Three major changes were observed in the activity of these polysensory medial thalamic neurons: (1) normally quiescent in the intact animal, about 70% of the neurons now dsiplayed spontaneous activity; (2) many of these spontaneously active neurons no longer responded to caudate stimulation and the responses to sensory stimulation were not changed; and (3) while caudate stimulation alone did inhibit some neurons, such stimulation in a conditioning test procedure often failed to inhibit the test response to limb stimulation which ‘broke through’ the inhibitory period. All of these changes were correlated with the extent of damage to the ipsilateral substantia nigra. Additionally, a noticeable change was observed in the behavior of the lesioned animals; intense circling, contralateral to the side of the lesion, persisted for several days following surgery. Other symptoms were arrest reactions, abnormal rhythmic pawing and sluggishness of movement. The results indicate that the substantia nigra is an important element in funneling caudatofugal activity to the centromedian-parafascicular complex where it interacts with, and modulates incoming sensory activity. The loss of this modulation and the removal of a tonic background inhibition, indicated by the increased proportion of spontaneously active neurons, may be important factors in producing the observed behavioral abnormalities.

Intracellular responses in the centrum medianum-parafascicular complex of the cat following medial and lateral caudate, substantia nigra and peripheral stimulation

Caudate, nigral and somatosensory stimulation generates brief EPSPs followed by prolonged IPSPs in thalamic neurons of the centromedian-parafascicular complex. A 300 msec long hyperpolarization and inhibition of neuronal excitability represents the predominant effect by virtue of its duration, intensity and constancy. The brief excitatory response which precedes the inhibition is more variable, depending largely upon the site of basal ganglia stimulation. EPSPs tend to remain subthreshold for lateral caudate stimulation whereas medial caudate, medial nigral and somatosensory stimulation usually generates an action potential prior to the inhibitory phase. Double shock stimulation of basal ganglia and limbs at variable intervals demonstrates the predominance of powerful inhibitory interactions between stratonigral and sensory inputs. The existence of these interactions indicates the importance of temporal factors in determining the momentary responsivity of medial thalamic neurons.

Electrophysiological studies of two types of thalamo-cortical neurones and their responses to stimulation of mesencephalic reticular formation.

1. Thalamo-cortical (T-C) neurones projecting their axons to the motor cortex were recorded intra- or extra-cellularly in the anterior ventral and lateral ventral nuclear complex of the thalamus in lightly nembutalized cats. The T-C neurones were identified as responding antidromically to stimulation of the motor cortex, and were examined in connection with effects of stimulation of the centrum medianumparafascicular complex (CM), pallidum (Pal), cerebellar nuclei (CN) and mesencephalic reticular formation (RF). 2. The T-C neurones were classified into two groups, A and B. The A-group neurones responded neither to stimulation of CM nor to that of Pal. By contrast, the B-group neurones were activated from either CM, Pal or both. The effect of RF stimulation was facilitatory in many of the A-group neurones whereas it was mostly inhibitory in the B-group neurones. CN stimulation activated most of the T-C neurones in both A and B groups. 3. The A-group neurones were categorized as the deep T-C neurones mediating the deep T-C response of the cortex (the early surface-positive-deep-negative component of the augmenting response) and the B-group neurones as the superficial T-C neurones mediating the superficial T-C response of the cortex (the recruiting response and the late surface-negative-deep-positive component of the augmenting response). Desynchronization of electrocorticograms in response to RF stimulation was suggested to result from inhibition of the superficial T-C neurones and facilitation of the deep T-C neurones.

Projections of the locus coeruleus and adjacent pontine tegmentum in the cat.

The projections of the locus coeruleus and adjacent pontine tegmentum have been studied using anatomical and physiological methods in the cat. Axonal trajectories were traced using either the Fink-Heimer I method following electrolytic lesions, or the autoradiographic method after injection of tritiated proline into the nucleus. Results with both methods were similar. Axons of locus noeruleus neurons ascended ipsilaterally through the mesencephalon lateral to the medial longitudinal fasiculus, ventrolateral to the central gray. In the caudal diencephalon, the ascending fibers entered the centrum medianum-parafascicular complex where they diverged into two fascicles: a dorsal fascicle which terminated in the intralaminar nuclei of the thalamus, and a ventral fascicle which gave off fibers to the ventrobasal complex and reticular nucleus of the thalamus while continuing centrolaterally into the lateral hypothalamus medial to the internal capsule. Fibers of the ventral fascicle ascended in the lateral hypothalamus and zona incerta and were traced through the preoptic region into the septum. Fibers could not be consistently traced to the cerebral cortex, and were not seen at all in the cerebellum. Throughout the ascending course of the path from the locus coeruleus, axons were given off to the pretectal area, the medial and lateral geniculate nuclei and the amygdala; fibers passed contralaterally through the posterior commissure, the midline thalamus, and the supraoptic commissure. Fibers descending from the locus coeruleus surrounded the intramedullary portion of the facial nerve and further caudally were observed ventrolateral to the hypoglossal and dorsal vagal nuclei. The axonal trajectories visualized with degeneration and autoradiographic methods followed closely those previously shown for reticular formation neurons, but were also similar to locus coeruleus projections revealed by histofluorescence methods. After injections of horseradish peroxidase into the centrum medianum-parafascicular complex, lateral hypothalamus or preoptic region, labeled neurons were located in the locus coeruleus, nucleus subcoeruleus, and lateral parabrachial nucleus. Reticular formation neurons were not labeled. Neurons in locus coeruleus and adjacent pontine tegmentum could be antidromically activated by stimulation in the rostral midbrain or caudal diencephalon. Our data indicate that both adrenergic and non-adrenergic neurons of the dorsolateral pontine tegmentum have similar projections.

Thalamo-cortical projections for recruiting responses and spindling-like responses in the parietal cortex

1. The thalamic neurones sending their axons to the parietal association cortex (middle suprasylvian gyrus) and receiving monosynaptic excitation from the cerebellar (interpositus or lateral) nucleus were recorded with microelectrodes extracellularly and intracellularly around the anterior ventral (VA) nucleus of the thalamus in cats. Such thalamic neurones are known to carry exclusively the impulses responsible for superficial thalamo-cortical (T-C) responses in the parietal cortex, being called superficial T-C neurones (see Sasaki et al., 1972a, b). 2. Repetitive (6--9/sec) stimulation of the centrum medianum-parafascicular complex (CM) or the intralaminar nuclei (IL) of the thalamus elicited grouped spike discharges of the neurone in synchronization with the recruiting responses in the parietal cortex. The grouped discharges usually preceded the respective cortical responses by several milliseconds. Numbers of the spikes in the grouped discharges increased and decreased as the recruiting responses waxed and waned on the repetitive stimulation. 3. The superficial T-C neurones also showed similar grouped discharges in synchronization with spindling-like, surface-negative cortical responses which occurred spontaneously or were evoked by single thalamic stimulation. 4. It was concluded that the superficial T-C neurons can convey impulses for recruiting responses and spindling-like responses from the thalamus directly to the cerebral cortex. They are supposed to constitute the final T-C pathway of the neuronal circuits of the recruiting system, i.e., non-specific T-C projection system.

Neurons of the Medial Diencephalon. II. Excitation of Central Origin

ArticleNeurons of the Medial Diencephalon. II. Excitation of Central OriginG. Krauthamer, P. Feltz, and D. Albe-FessardG. Krauthamer, P. Feltz, and D. Albe-FessardPublished Online:01 Jan 1967https://doi.org/10.1152/jn.1967.30.1.81MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited BySomatosensory evoked potential recovery in Kii amyotrophic lateral sclerosis/parkinsonism–dementia complex (Kii ALS/PDC)Clinical Neurophysiology, Vol. 114, No. 3Recovery functions of somatosensory evoked potentials in parkinsonian patientsJournal of the Neurological Sciences, Vol. 108, No. 1Somatosensory neurons projecting from the superior colliculus to the intralaminar thalamus in the ratBrain Research, Vol. 523, No. 2Thalamic nucleus ventro-postero-lateralis inhibits nucleus Parafascicularis response to noxious stimuli through a non-opioid pathwayBrain Research, Vol. 280, No. 2Thalamic mediodorsal nucleus and memory: A critical evaluation of studies in animals and manNeuroscience & Biobehavioral Reviews, Vol. 6, No. 3Peripheral and central substrates involved in the Rostrad transmission of nociceptive informationPain, Vol. 13, No. 1Behavioral alterations and loss of caudate modulation in the centrum medianum-parafascicular complex of the cat following electrolytic lesions of the substantia nigraBrain Research, Vol. 208, No. 1Intracellular responses in the centrum medianum-parafascicular complex of the cat following medial and lateral caudate, substantia nigra and peripheral stimulationNeuroscience Letters, Vol. 21, No. 2The afferent projections to the centrum medianum of the cat as demonstrated by retrograde transport of horseradish peroxidaseBrain Research, Vol. 184, No. 2Differential synaptic modulation of polysensory neurons of the intralaminar thalamus by medial and lateral caudate nucleus and substantia nigraBrain Research, Vol. 154, No. 1Processing of sensory informationProgress in Neurobiology, Vol. 9, No. 1-2Effects of medial thalamic lesions in the rat a review and an interpretationNeuropsychologia, Vol. 9, No. 2Basal ganglia-diencephalon synaptic relations in the cat. II. Intracellular recordings from dorsal thalamic neurons during low frequency stimulation of the caudatothalamic projection systems and the nigrothalamic pathwayBrain Research, Vol. 27, No. 1Basal ganglia-diencephalon synaptic relations in the catBrain Research, Vol. 20, No. 2Caudate nucleus lesions and perseverative behaviorPhysiology & Behavior, Vol. 4, No. 4Responses of cat pallidal neurons to cortical and subcortical stimuliExperimental Neurology, Vol. 20, No. 4Avoidance and escape behavior following striatal lesions in the ratExperimental Neurology, Vol. 20, No. 2Some problems associated with interpretation of physiological and behavioral responses to stimulation of caudate and thalamic nucleiBrain Research, Vol. 6, No. 1Structural organization of nonspecific thalamic nuclei and their projection toward cortexBrain Research, Vol. 6, No. 1 More from this issue > Volume 30Issue 1January 1967Pages 81-97 Copyright & PermissionsCopyright © 1967 the American Physiological Societyhttps://doi.org/10.1152/jn.1967.30.1.81History Received 5 April 1966 Published online 1 January 1967 Published in print 1 January 1967 Metrics