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Functional connectivity between the red nucleus and the hippocampus supports the role of hippocampal formation in sensorimotor integration.

Experiments were carried out in urethane-anesthetized rats to evaluate the hypothesis that the red nucleus has functional connections with the hippocampal formation. Depth profiles of electrical stimulation in experiment 1 confirmed that stimulation administered to the red nucleus elicited theta field activity in the hippocampal formation with a linear relationship between stimulus intensity and theta frequency. Experiment 2 showed that microinfusion of local anesthetic procaine hydrochloride into the medial septum resulted in a reversible blockade of theta field activity elicited by electrical stimulation of the red nucleus. In experiment 3, the discharge activity of red nucleus cells was recorded during the field conditions of hippocampal synchrony (theta) and hippocampal asynchrony [large amplitude irregular activity (LIA)]. Analysis revealed that 26/46 (56%) of red nucleus cells were theta-related, whereas the remaining 20 (44%) were nonrelated. The majority of theta-related cells were classified as tonic theta-on. A brief increase above the basal discharge rate of tonic theta-on red nucleus cells during LIA predicted the transition from LIA to theta with 400- to 500-ms latency. Furthermore, higher frequency transitional discharges predicted higher theta frequencies, whereas higher discharge rates during theta predicted shifts to higher theta frequencies. The results supported the conclusion that the red nucleus, traditionally associated with motor functions, is functionally connected with the neural circuitry involved in the generation of theta band oscillation and synchrony in the hippocampal formation, in agreement with the predictions of the sensorimotor integration model of hippocampal function.

Anesthetics, Local↗

Neuronal activity in rat red nucleus during forelimb reach-to-grasp movements.

The activity of 259 task-related red nucleus neurons was recorded using chronic electrophysiological methods in free moving rats. Modulations in activity were analysed in relation to onset (first detected wrist movement) and end (arrival of the paw over the food) of a reach-to-grasp movement. Excitatory peaks were found to begin before, during and after the reach, but there were clear peaks in the distribution of onset times after reach-onset and before reach-end, reflecting the fact that one third of all peaks began specifically during the reach, although this occupied only a small fraction of the analysis time. Both excitations and inhibitions showed a strong tendency to end in close temporal association with reach-end. Analysis of excitatory modulation amplitudes showed that the largest peaks were formed when data was aligned to reach-end, and that these largest peaks nearly all began during the reach and ended precisely at the time the paw would have been about to grasp the food. The spread of neural activation onset times throughout the course of the complex reach-to-grasp movement is consistent with a relationship of individual neurons in the rat red nucleus with movements of all parts of the forelimb, as would be expected if all limb muscle groups are represented in the nucleus. On the other hand the disproportionate number of modulations that occur during the reach and their strong alignment with time of reach-end suggests there is a bias in red nucleus function towards the control of distal motions associated with accurate grasp, consistent with the result of recent lesion studies. This provides indirect evidence that functionally the rat red nucleus may be organized in a similar way to that of monkeys, in which an important role in control of accurate distal movements is well established. The possibility is discussed that red nucleus offers a timing signal for co-ordination of movements across joints, in particular the precise distal-proximal binding normally seen in accurate reach-to-grasp movements.

Action Potentials↗

Projections from the dorsal column nuclei and the spinal cord to the red nucleus in cat.

The projections of the red nucleus (RN) from the dorsal column nuclei (DCN) and the spinal cord have been investigated in cats with the degeneration method. After electrolytic DCN lesions and unilateral cordotomies including the lateral and ventral funiculi, the degeneration was studied in Fink-Heimer stained sections. Contralateral to a DCN lesion terminal degeneration was found along the whole rostrocaudal extent of the red nucleus. In most portions the degeneration was scattered, but dense zones were present, too. Terminal fibers were present in both magnocellular and parvocellular parts. After a gracile lesion the degenerating fibers were restricted to the ventral part of the RN, while the terminal patterns did not differ significantly after cuneate and large DCN lesions. The spinal fibers were found ipsilateral to the cordotomy. Like the DCN fibers, the spinal fibers were present along the whole rostrocaudal extent of the RN and in both magno- and parvocellular zones. Their distribution in the transverse plane was similar, as well. However, the present material was not sufficient to show subtle differences between the DCN and spinal projections, nor to show a possible somatotopical organization of the spinal projection.

Animals↗

Pattern of pyramidal tract collateralization to medial thalamus, lateral hypothalamus and red nucleus in the cat.

Stimulating electrodes were placed in the red nucleus, lateral hypothalamus and medial thalamus in order to determine whether pyramidal tract (PT) neurons send collaterals to those sites. The red nucleus projections are well-known, but it was discovered that PT neurons also project into the other two sites. All of the fibers that sent collaterals to all three sites originated from fast PT neurons. Those that responded to stimulation of the skin and that sent collaterals to two or three sites were predominantly fast PT neurons. Those neurons that responded only to cerebral peduncle stimulation were predominantly slowly-conducting, when compared with the set of PT neurons in response to cerebral peduncle stimulation. The patterns of collateral branching to red nucleus and to lateral hypothalamus were similar, suggesting a similar synaptic effect of the pyramidal system in the two sites. Measurement of the speed of conduction from three sites along the length of corticospinal fibers revealed large changes on some, but not all, fibers; there was no evident pattern to these changes that might be associated with collateral branching. A new hypothesis concerning the functional role of fast PT neurons in regulating movement is presented.

Anesthesia↗

Decrease in choline acetyltransferase and in high affinity glutamate uptake in the red nucleus of the cat after cerebellar lesions.

Acetylcholine (ACh) is suggested to be a neurotransmitter in cerebellothalamic and cerebellorubral fibres. We therefore measured choline acetyltransferase (CAT) activity in the cat red nucleus after lesion of the contralateral cerebellum. Decreased CAT activity was obtained (-37%), specifically localized in the red nucleus and particularly in its rostral parvocellular part. Since the red nucleus of the cat displays rather low CAT levels, the possible cholinergic input seems not be sufficient to explain the powerful action of the cerebellum on red nucleus magnocellular neurons. As glutamic acid (Glu) may be the neurotransmitter of many excitatory systems in the brain, we measured high affinity Glu uptake in the red nucleus after lesions of the contralateral cerebellum. Results showed a decreased (-35%) Glu activity restricted to the red nucleus and particularly in its caudal magnocellular part.

Animals↗

Antidromic and synaptic activation of Deiters' neurons induced by stimulation of red nucleus in the cat.

Antidromic and orthodromic action potentials of neurons located in the lateral vestibular nucleus of Deiters' evoked by stimulation of red nucleus were studied in anaesthetized cats. Vestibulospinal neurons were identified by stimulation of the lateral vestibulospinal tract. The 'second-order' vestibular neurons were revealed by mean of stimulation of the ipsilateral VIIIth nerve. Stimulation of the red nucleus is shown to lead mainly to antidromic, as well as mono-, oligo- and polysynaptic activation of Deiters' neurons. Not any inhibitory reaction was observed in vestibular neurons in response to stimulation of the red nucleus. Ascending axon collaterals of the vestibulospinal neurons to this brainstem structure were revealed. The peculiarities and functional significance of the effects mentioned are discussed.

Action Potentials↗

Somatotopic studies on red nucleus: spinal projection level and respective receptive fields.

The somatotopic inputs into red nucleus (RN) neurons have been studied with special reference to their level of projection in the spinal cord. As inputs we employed either volleys in predominantly cutaneous nerves of forelimb and hindlimb or cutaneous mechanoreceptor discharges evoked by taps to footpads of forelimb and hindlimb. There has been physiological confirmation of the anatomical findings that RD neurons projecting to the lumbar cord are located in the ventrolateral zone of the pars magnocellularis, whereas in the dorsomedial zone are RN neurons with cervical but not lumbar projection. Somatotopically there was found to be a differentiation of input to RN neurons according as they projected to the lumbar or only to the cervical cord. This finding was presented in the form both of tables and of somatotopic maps. As expected, this discrimination was more restrictive for the more selective inputs from pad taps than for nerve inputs. Nevertheless, forelimb inputs often had a considerable excitatory and inhibitory action on lumbar-projecting RN neurons, and vice versa for cervical-projecting neurons. There were two notable somatotopic findings that suggest specificities of connectivities. First, despite the large convergence of IP neurons onto RN neurons (about 50-fold), the degree of somatotopic discrimination was about the same for interpositus and RN neurons with two testing procedures: between inputs from forelimb and hindlimb; and between inputs from pads on one foot. Second, although there was in the interpositus nucleus a considerable topographical admixture of neurons with dominant forelimb or hindlimb inputs, the axonal projections of these neurons were apparently unscrambled on the way to the target RN neurons, so as to deliver the somatotopic specificities observed for two classes of RN neurons; those projecting down the spinal cord beyond L2 level, and those projecting to C2 but not L2. Finally, there is a general discussion of motor control with reference to the pathway; pars intermedia of anterior lobe of cerebellum leads to interpositus nucleus leads to red nucleus leads to rubrospinal tract leads to spinal motoneurons.

Animals↗

The compensatory role of the parvocellular division of the red nucleus in operantly conditioned rats.

To assess the role of the parvocellular division of the red nucleus in motor control, rats were operantly conditioned to walk on a rotating bar and their red nuclei were lesioned with the fiber sparing agent, quinolinic acid. Since both parvocellular and magnocellular divisions of the red nucleus overlap in the rat, they both became involved in this lesion. To differentiate between them, two paradigms were used. (1) Prior to the lesion, the magnocellular division was dysfunctioned by transecting its spinal output, namely, the rubrospinal tract, in the dorso-lateral funiculus (DLF) of the spinal cord. After compensation for this transection had occurred in a few days, the red nucleus was lesioned with quinolinic acid. Rats again compensated rapidly, suggesting that the remaining red nuclear outflow systems, such as the rubro-olivary tract, play no detectable role in the control of on-going movements. (2) In the second paradigm, the red nucleus was lesioned without a preceding DLF transection. This lesion involved both the rubro-bulbar and rubro-spinal projections. Rats did not compensate, or did so very slowly. For compensation to occur, therefore, rubro-bulbar projections need to be intact. This suggests that such projections, that include the rubro-olivary tract, play a role in the compensation for DLF transections.

Animals↗

Red nucleus: past and future.

The red nucleus has greatly interested scientists for almost a century. This can be explained by the fact that problems of general interest are encountered when studying this nucleus. Some of them are outlined in this paper, such as the phylogenetic evolution of the rubrospinal tract, the respective roles of the rubrospinal and pyramidal tracts in the execution of various types of movements, and the respective roles of these two tracts in movement automatization.

Animals↗

Neurochemical significance of the red nucleus.

This study reviews some of the more prominent reports related to neuromelanin and the physiological significance of the substantia nigra and the red nucleus. The phylogenetic and ontogenetic parallelism between these two structures is considered. The presence of dopachrome in the red nucleus and of neuromelanin in the substantia nigra is discussed. An experimental study in four human brains in which the red nucleus was injected with zinc sulfate showed the presence of neuromelanin in the red nucleus. This is the first reported demonstration that dopachrome present in the red nucleus is the precursor of neuromelanin.

Adult↗

Alpha 2- and beta-adrenoceptors differentially modulate GABAA- and GABAB-mediated inhibition of red nucleus neuronal firing.

In mesencephalic red nucleus (RN), GABA-induced inhibition of neuronal firing is modulated by noradrenaline acting on alpha2- and beta-adrenoceptors. Since both GABAA and GABAB receptors are present in the rat RN, we have recorded the firing activity of RN neurons in vivo from anaesthetized rats to study how GABAA- and GABAB-mediated effects are modulated by either alpha2- or beta-adrenoceptor activation. Both the GABAA agonist isoguvacine and the GABAB agonist baclofen depressed the firing of RN neurons. During simultaneous application of clonidine, an alpha2-adrenoceptor agonist, half of the isoguvacine- and baclofen-mediated responses were modified: isoguvacine-mediated inhibition was enhanced by 97% without any change in effect duration, whereas baclofen responses were either increased or slightly reduced in the same number of cases. Application of isoprenaline, a beta-adrenoceptor agonist, increased isoguvacine effect in 66% of neurons without modifying effect duration; the amount of increase (43%) was significantly lower than that induced by clonidine. On the other hand, in the presence of isoprenaline, baclofen response was reduced in 72% of neurons with respect to both the amount (52%) and the duration (34%) of effect. Taken together, these results indicate that alpha2-adrenoceptors mainly enhance GABAA-induced inhibition and induce mixed effects on GABAB response; on the other side, beta-adrenoceptors exert an opposite modulation on GABA effects, respectively, enhancing and depressing GABAA- and GABAB-mediated responses.

Action Potentials↗

Heterogeneous distribution of neurons containing calbindin D-28k and/or parvalbumin in the rat red nucleus.

The cellular localization of calbindin D-28k (CB) and parvalbumin (PV) in the red nucleus of the rat was studied by means of double-immunohistochemical techniques applied to single sections. Neurons displaying immunoreactivity for either CB or PV were found throughout the rostrocaudal extent of the red nucleus, but PV neurons predominate in the rostral two-thirds and CB neurons in the caudal two-thirds of the nucleus. Likewise, there was a clear but not absolute segregation of the two types of neurons along the dorsoventral axis; PV and CB neurons were largely confined to the dorsolateral and ventromedial sectors of the nucleus, respectively. Most CB neurons were large (> 30 microns), whereas large and medium-sized (15-30 microns) PV neurons were equally abundant. Additionally, some large and medium-sized neurons displaying immunoreactivity for both PV and CB were encountered in the ventromedial sector of the red nucleus. The present study reveals that, in contrast to previous beliefs, the red nucleus is composed of a neuronal population that is chemically highly heterogeneous.

Animals↗

Afferents to the red nucleus in the lizard Podarcis hispanica: putative pathways for visuomotor integration.

The afferents to the red nucleus from visual and nonvisual forebrain centers have been investigated in the lizard Podarcis hispanica by using both retrograde and anterograde transport of tracers. Because the red nucleus constitutes a key structure in the limb premotor system, these sensory afferents probably are involved in visuomotor and other forms of sensorimotor integration. After tracer injections aimed at the red nucleus, retrograde labeling was found in the reticular thalamus, the subthalamus, the nucleus of the posterior commissure, as well as in two retinorecipient nuclei, namely, the ventral lateral and pretectal geniculate nuclei, where labeled cells are especially abundant. These geniculorubral projections have been confirmed by means of anterograde tracing with dextranamine injections. On the other hand, small injections of tracers in the retina demonstrated that its projections to the ventral lateral and pretectal geniculate nuclei are organized in a point-to-point fashion. Moreover, small tracer injections into the optic tectum of Podarcis indicated that the ventral lateral geniculate nucleus also receives a precisely organized tectal afferent. Taken together, these results strongly suggest that geniculorubral projections might constitute the neuroanatomical substrate for the generation of quick locomotor responses to appropriate visual stimuli. Additional ventral thalamic, subthalamic, and pretectal afferents to the red nucleus are likely to subserve other kinds of sensorimotor integration. These results help to clarify the organization of the reptilian motor system, including the telencephalic control of motor responses, and to unravel some of the major trends in the evolution of the limb premotor network of tetrapodian vertebrates.

Afferent Pathways↗

Comparison of the effects of electrolytic and chemical destruction of the red nucleus on the compensatory capacity of rats with rubrospinal tract lesions.

Transection of the rubrospinal tract in rats, performed before lesion of the red nucleus, resulted in the facilitated recovery of motor activity and operantly conditioned reflexes. Such facilitation was absent when the red nucleus is lesioned alone. This phenomenon is explained by the switching of descending influences on the corticospinal tract through the participation of the following system: red nucleus--inferior olive--cerebellum--ventrolateral thalamic nucleus--cerebral cortex. The above mentioned facilitating influence on the recovery process was particularly prominent in rats with quinolinic acid-induced lesion of the red nucleus. Under these conditions, the cerebellar ascending fibers to the ventrolateral thalamic nucleus were preserved. Decreased facilitated recovery following electrolytic lesion of the red nucleus suggests the existence of additional cerebello-cortical pathways for the realization of the switching phenomenon.

Animals↗

Volumetric studies on the red nucleus of the rat at different ages.

The postnatal development of the red nucleus in albino rat was quantitatively studied. Planimetric studies on stained paraffin sections of the midbrain showed that the red nucleus has a rounded contour with tapering ends and a broad centre. The volume of the red nucleus revealed an increase from birth, to reach its maximum at the age of 3 months, then declines until the age of 2 years. However, the size does not regain its newly born value. On the other hand, the number of cells remains constant during the entire life span of the animal.

Age Factors↗

Inferior olive destruction induces dysfacilitation of the red nucleus activity.

The spontaneous discharge frequency of the red nucleus neurones was evaluated in rat before and after total destruction of the inferior olive with the 3-acetylpyridine. It was found that the sustained firing recorded in the control animals (33.7 +/- 23.7/s) drastically decreased to a low rate (4.6 +/- 7.1/s) after the intoxication. This effect took place between 2 h 15 min and 2 h 45 min after the injection. which is the critical period corresponding to the inferior olive degeneration and the consequent climbing fiber deafferentation. It lasted at least as long as the acute experiment. The conclusions are reached that the inferior olive destruction leading to an enhanced cerebellar inhibition, produces a dysfacilitatory effect on the red nucleus neurones.

Animals↗

Evidence for reactive synaptogenesis in the ventrolateral thalamus and red nucleus of the rat: changes in high affinity glutamate uptake and numbers of corticofugal fiber terminals.

High affinity glutamate uptake into corticofugal fiber terminals was measured in the ventrolateral thalamus and red nucleus at varying time intervals after lesions were made by kainic acid in the contralateral interpositus nucleus of the cerebellum in rats. Under similar conditions the density of cortical fiber terminals was estimated using the Fink-Heimer impregnation technique. 1. Glutamate uptake steadily increased in the ventrolateral thalamus up to 60 days after lesions in the contralateral cerebellum. 2. Similar changes were noted in the red nucleus. 3. The changes were dependent on the integrity of corticofugal fibers to the thalamus and red nucleus. 4. No changes in uptake of gamma-aminobutyric acid were noted. 5. Saturation curves for glutamate uptake suggested a change in the maximal number of transport sites. 6. Fink-Heimer degeneration studies showed an increase in cortical terminals in the ipsilateral ventrolateral thalamus and in both rostral and caudal regions of the red nucleus following lesions in the contralateral interpositus nucleus. The data are consistent with an increase in the number of cortical fiber terminals in reaction to loss of cerebellar input to the ventrolateral thalamus and red nucleus. This study correlates anatomical and biochemical evidence for collateral sprouting in a model based on electrophysiologic data in the red nucleus and extends the model to include the thalamus.

Animals↗

Effects of red nucleus microstimulation on the locomotor pattern and timing in the intact cat: a comparison with the motor cortex.

Effects of red nucleus microstimulation on the locomotor pattern and timing in the intact cat: a comparison with the motor cortex. To determine the extent to which the rubrospinal tract is capable of modifying locomotion in the intact cat, we applied microstimulation (cathodal current, 330 Hz; pulse duration 0.2 ms; maximal current, 25 microA) to the red nucleus during locomotion. The stimuli were applied either as short trains (33 ms) of impulses to determine the capacity of the rubrospinal tract to modify the level of electromyographic (EMG) activity in different flexors and extensors at different phases of the step cycle or as long trains (200 ms) of pulses to determine the effect of the red nucleus on cycle timing. Stimuli were also applied with the cat at rest (33-ms train). This latter stimulation evoked short-latency (average = 11.8-19.0 ms) facilitatory responses in all of the physiological flexor muscles of the forelimb that were recorded; facilitatory responses were also common in the elbow extensor, lateral head of triceps but were rare in the physiological wrist and digit extensor, palmaris longus. Responses were still evoked in most muscles when the current was decreased to near threshold (3-10 microA). Stimulation during locomotion with the short trains of stimuli evoked shorter-latency (average = 6.0-12.5 ms) facilitatory responses in flexor muscles during the swing phase of locomotion and, except in the case of the extensor digitorum communis, evoked substantially smaller responses in stance. The same stimuli also evoked facilitatory responses in the extensor muscles during swing and produced more complex effects involving both facilitation and suppression in stance. Increasing the duration of the train to 200 ms modified the amplitude and duration of the EMG activity of both flexors and extensors but had little significant effect on the cycle duration. In contrast, whereas stimulation of the motor cortex with short trains of stimuli during locomotion had very similar effects to that of the red nucleus, increasing the train duration to 200 ms frequently produced a marked reset of the step cycle by curtailing stance and initiating a new period of swing. The results suggest that whereas both the motor cortex and the red nucleus have access to the interneuronal circuits responsible for controlling the structure of the EMG activity in the step cycle, only the motor cortex has access to the circuits responsible for controlling cycle timing.

Animals↗