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Long term modification of rubral activity after inferior olive destruction.

The long term effects of the inferior olive degeneration on red nucleus activity were studied in the rat. The animals were injected with 3-acetylpyridine to produce a pharmacological destruction of the inferior olive and were then used for acute experiments at 1-2, 5-7, 14-18, 29-37, 81-110 and 236-255 days later. After degeneration of the inferior olive, there was an 'initial period' lasting for a few days, characterized by a low discharge frequency of the red nucleus neurones. A 'period of adaptation' followed during the first month, characterized by a slow recovery towards the control firing rates of the rubral units. Nevertheless, the temporal distribution of the discharges was not recovered since the firing became organized in a bursting activity. From 1 up to 8 months, the normal unit activity was not restored. The hypothesis is advanced that the suppression of the inferior olive which increases the cerebellar inhibition, produces a consequent disfacilitation of red nucleus activity which persists for a few days. Then at increasing survival times, a progressive compensation takes place without a real restoration of the initial rubral activity.

Action Potentials↗

The isomers of thioctic acid alter C-deoxyglucose incorporation in rat basal ganglia.

Nigral cell death in Parkinson's disease is associated with decreased reduced glutathione (GSH) levels, impaired complex I activity and inhibition of alpha-ketoglutarate dehydrogenase (alpha-KGDH) in substantia nigra. Thioctic acid exerts antioxidant activity through a thiol-disulphide redox couple and is an essential cofactor for alpha-KGDH. However, it is not known whether or not thioctic acid enters basal ganglia or exerts beneficial effects in Parkinson's disease. As a global measure of altered cerebral function, the effect of R- and S-thioctic acid on 14C-2-deoxyglucose (14C-2DG) incorporation was investigated in rats. Rats were treated with either R- or S-thioctic acid (50 mg/kg IP) or 0.9% saline acutely or for 5 days and 14C-2DG incorporation in basal ganglia was assessed. Following acute administration, R- but not S-thioctic acid caused an overall increase in 14C-2DG incorporation that was significant in both substantia nigra zona compacta and zona reticulata. R-thioctic acid also increased the incorporation of 14C-2DG in the medial forebrain bundle, thalamus, and red nucleus. S-thioctic acid decreased 14C-2DG incorporation in the subthalamic nucleus, but increased it in the red nucleus. Following repeated administration, R-thioctic acid no longer increased 14C-2DG incorporation in either zona compacta or zona reticulata of substantia nigra. However, both R- and S-thioctic acid now decreased 14C-2DG incorporation in the subthalamic nucleus. The data suggest that thioctic acid does enter the brain can alter neuronal activity in areas of the basal ganglia intimately associated with the motor deficits exhibited in Parkinson's disease.

Animals↗

Multiplex in-cell reverse transcription-polymerase chain reaction for the simultaneous detection of p210 and p190 BCR-ABL mRNAs in chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia cell lines.

We designed a novel multiplex in-cell reverse transcription-polymerase chain reaction method for the simultaneous detection and differentiation of p190 and p210 BCR-ABL mRNAs within single cells from the human chronic myeloid leukemia and Philadelphia positive acute lymphoblastic leukemia. Human K562 chronic myeloid leukemia and SUP B-15 Ph+ acute lymphoblastic leukemia cell lines were used as positive controls for p210 and p190 BCR-ABL mRNAs, respectively. HL60 cell line was used as a negative control. After the leukemia cells were fixed and permeabilized, without extracting nucleic acids, the mRNAs were reverse transcribed to cDNAs, and the cDNAs were amplified by multiplex polymerase chain reaction with fluorescent primers specific for p190 and p210 BCR-ABL mRNAs. After transfer onto glass slides by cytospin, the amplified cells were detected by fluorescence microscopy. Fluorescence microscopy after propidium iodide or 4',6-diamidino-2-phenylindone counterstaining showed that the positive K562 cells exhibited a yellow-green fluorescent cytoplasm around a red nucleus, and that the positive SUP B-15 cells exhibited an orange cytoplasm around a blue nucleus. Only the red or blue nucleus was visible in respective negative HL60 cells. The specificity of amplification was confirmed by the absence of a signal when control experiments were performed either with RNase digestion of mRNA or without reverse transcriptase/Taq polymerase. We conclude that the multiplex in-cell reverse transcription-polymerase chain reaction method is capable of simultaneously detecting and differentiating the p210 and p190 BCR-ABL mRNAs of chronic myeloid leukemia and Philadelphia-positive acute lymphoblastic leukemia cells, and that it may be useful in quantitatively monitoring the minimal residual disease during therapy.

DNA Primers↗

Pyramidal tract and corticospinal neurons with branching axons to the dorsal column nuclei of the cat.

Extracellular single activity was recorded from pericruciate neurons in anaesthetized, paralysed, artificially ventilated cats. A total of 309 neurons were identified antidromically by stimulation of the dorsal column nuclei (229 from the nuneate nucleus and 80 from the gracile nucleus). The study addressed the question whether pericruciate-dorsal column nuclei neurons (corticonuclear cells) sent collaterals to the ipsilateral red nucleus and/or to the contralateral nucleus reticularis gigantocellularis. Also, the ipsilateral pyramidal tract was stimulated at mid-olivary level, as was the crossed corticospinal tract at C2, Th2 and L2 levels in order to know whether the corticonuclear cells sent their axons to the spinal cord and if so to which level. It was found that more than 95% of the corticonuclear fibres coursed through the pyramidal tract. A significant (28.4%; 88/309) proportion of the the corticonuclear neurons sent collaterals to the red nucleus and/or to the nucleus reticularis gigantocellularis. About 68% (209/309) of the corticonuclear cells did not send their axons to the spinal cord and the remainder were corticospinal neurons. Most of the corticospinal fibres terminated at the cervical level (72/100) and the remaining ended at thoracic (18/100) and lumbar (10/100) segments of the cord. While 63.4% (123/194) of the corticonuclear fibres coursing through the pyramidal tract and ending at supraspinal levels were slow conducting, the great majority of the corticospinal neurons were fast conducting (91/100). The non-corticospinal neurons were significantly slower conducting than the corticospinal cells. The corticogracile neurons were slower conducting than the corticocuneate cells. Of the 88 corticonuclear neurons that sent at least a branch to the sites tested, 50% branched into the red nucleus, 35.2% into the nucleus reticularis gigantocellularis and 14.7% into both nuclei, without significant difference between non-corticospinal and corticospinal cells. Most of the main axons of the corticonuclear cells ended at bulbar and cervical levels (281/309 or 90.9%). The data indicate that pericruciate-dorsal column nuclei neurons form a particular substrate within pyramidal tract cells. They can serve precise functions in motor coordination associated with the selection of their own sensory input. The results are discussed from this point of view.

Animals↗

Developmental plasticity of the rubrospinal tract in the North American opossum.

We have shown previously that rubral axons can grow caudal to a lesion of their pathway at thoracic levels of the spinal cord in the developing opossum, Didelphis virginiana. In the present report we expand on that observation and present evidence which suggests that the critical period for plasticity of the rubrospinal tract ends earlier at cervical than at thoracic levels. In addition, we show that most rubrospinal neurons die as a result of axotomy during early stages of the critical period. The opossum was chosen for study because the development of its rubrospinal tract occurs after birth. In one set of experiments the area containing the rubrospinal tract was lesioned at cervical or thoracic levels and after 30 days or more, retrograde transport techniques were used to determine if rubral axons had grown caudal to the lesion. When the lesions were made at rostral cervical levels between estimated postnatal day 26 and maturity, neurons could not be labeled in the contralateral red nucleus by injections of retrograde markers ipsilateral to the lesion and caudal to it. We were not able to obtain adequate survival after cervical lesions made prior to estimated postnatal day 26. When the lesions were made at mid to caudal thoracic levels between estimated postnatal days 19 and 26, neurons could be labeled in the contralateral red nucleus. When comparable lesions were made at estimated postnatal day 40, there was usually a decrease in the number of labeled neurons, and when they were made at estimated postnatal day 54, none was labeled. In selected cases, operated at estimated postnatal day 19, cell counts provided evidence for loss of neurons in the red nucleus contralateral to the lesion. In orthograde transport experiments performed on animals with thoracic lesions of the rubrospinal tract made between estimated postnatal days 18 and 33, rubral axons could be labeled caudal to the lesion, and they seemed to take the most direct route around it. Although they sometimes assumed abnormal positions caudal to the lesion, rubral axons appeared to reach areas of the gray matter appropriate to them. When lesions were made at estimated postnatal day 54 or in older animals, labeled axons could be traced to the lesion site but not caudal to it.(ABSTRACT TRUNCATED AT 400 WORDS)

Amidines↗

Discharge of identified deep cerebellar nuclei neurons related to eye blinks in the alert cat.

The activity of identified cerebellar nuclear neurons was recorded in the alert cat during blinks induced by corneal air puffs, light flashes and tones. Eyelid response to air puffs consisted of an early (16.5 +/- 2.7 ms) downward movement followed by two to three late downward steps. Blinks induced by flashes or tones presented longer latencies (52.6 +/- 4.8 and 50.1 +/- 8.0 ms). Type A neurons (n = 86) increased their spike activity in coincidence with the beginning of the blink, regardless of the stimulus modality. The late eyelid downward responses were accompanied by corresponding increases in the firing rate of the neuron. Type A neurons were activated mostly from the red nucleus (48/86) or the restiform body (24/86). Type B neurons (n = 30) fired a brief burst of spikes slightly preceding the blink, followed by a noticeable decrease in their firing rate. As for type A, the discharge response of type B neurons was always the same regardless of the sensory modality. These neurons were activated from the red nucleus (18/30), oculomotor complex (6/30) and restiform body (6/30). Although no precise temporal coupling was found between the beginning of the neuronal response and the start of either the stimulus or the motor response, linear regression analysis demonstrated significant relationships between mean firing rate of type A and B neurons and eyelid position, velocity and/or acceleration. Deep cerebellar nuclei neurons presented here seem to be directly involved in the execution of reflexively induced blinks following the smaller details of eyelid motor performance. The opposite behavior of type A and B cells suggests an interplay of reciprocal actions to determine the ongoing displacements of the lid. Finally, the cerebellum seems to influence blinks through a spread action on many brainstem sites and not exclusively on the red nucleus.

Acoustic Stimulation↗

Reorganization of cerebellorubral terminal fields following hemispherectomy in adult cats.

Tritiated amino acids were injected into the right nucleus interpositus of the cerebellum and the projections to the red nucleus were mapped autoradiographically in adult cats with ablation of the left cerebral hemisphere and in intact controls. In intact animals cerebellorubral terminals were found along the entire rostrocaudal extent of only the left red nucleus. The fields occupied a larger area and were apparently more dense toward the middle third of the nucleus. An outstanding change in hemispherectomized cats was a significant expansion of the terminal fields into the dorsal quadrants. Possibilities for morphological reorganization are discussed.

Animals↗

Functional MRI-BOLD of brainstem structures during visually triggered migraine.

BACKGROUND: Previously, hyperoxia and blood volume increase were reported in the red nucleus and substantia nigra during spontaneous migraine with aura. OBJECTIVE: To further understand the pathophysiologic role of these centers, activation of brainstem structures was investigated in patients with visually triggered migraine. METHODS: Twenty-six patients with migraine (23 with aura and 3 without aura), and 10 normal control subjects were studied with blood oxygen level-dependent (BOLD) fMRI during repeated checkerboard visual stimulation. Three axial image sections, which covered the occipital cortex and brainstem, were acquired 224 times with a temporal resolution of 3.5 seconds. RESULTS: Repetitive visual stimulation triggered symptoms in 12 patients; four who had migraine with aura developed both visual symptoms and headaches, and six who had migraine with aura and two who had migraine without aura had headaches only. Four patients who had migraine with aura experienced the onset of their usual aura or onset of their typical headache either during the experiment or immediately after. In the remaining 10 patients with migraine, and all control subjects, visual stimulation failed to trigger symptoms at any time. In 75% of the patients who developed symptoms during stimulation, baseline T2*-weighted MR signal intensities increased in the red nucleus and substantia nigra before occipital cortex signal elevation or the onset of visually triggered symptoms. CONCLUSION: Activation (hyperoxia and blood volume increase) of the red nucleus and substantia nigra in association with visually triggered symptoms of migraine suggest that these brainstem structures are a part of a neuronal network activated during an attack.

Adult↗

[Oculomotor nerve palsy due to small midbrain infarct--functional topography based on MRI findings].

This is a report of 3 cases presented with oculomotor nerve palsy caused by small midbrain infarct. The aim of this report is to clarify the functional topography of intranuclear and intrafascicular portion of the oculomotor nerve with MRI. Three cases are 2 males and 1 female, ranging 51 to 68 years in age. Except for the long tract signs at the acute stage, cardinal sings were all eye-related, incomplete in 1 case and pupil sparing-type in 2 cases. In MRI, the size of the lesion extended 5 to 12 mm. In the incomplete palsy case, the infarction extended from the level immediately below the 3rd ventricle into the whole length of midbrain, whereas in the pupil-sparing types, more limited lesion excluding the upper part of the midbrain was noted. Anatomically the longitudinal size of the nucleus is 10mm and nerves functionally related to pupil reaction, eye motion and eyelid elevation are arranged in rosrocaudal order. Therefore, it is speculated that in midbrain, intrafascicular location of nerve fibers associated with pupil reaction is rostral and oculomotor nerve palsy of pupil sparing type is caused by the lesion excluding the rostral midbrain. MRI findings of the present 3 cases are compatible with this speculation. The lowest border of red nucleus is at the level of superior colliculus, whereas oculomotor nucleus has its lowest margin at the inferior colliculus. Therefore, red nucleus becomes an informative landmark to visualized the level of oculomotor nerve injury, since the red nucleus is clearly demonstrated in high intensity in T2 weighted image.

Aged↗

On the absence of a rubrothalamic projection in the monkey with observations on some ascending mesencephalic projections.

In order to determine whether there is a rubrothalamic projection in the rhesus monkey, the ascending degeneration resulting from electrolytic lesions made in the red nucleus and adjacent mesencephalon in animals surviving at least one year after bilateral interruption of the superior cerebellar peduncles (PCS) was studied by means of the Fink-Heimer technique. In a necessary preliminary step it was shown that virtually all of the degeneration disappeared from the thalamus within twelve months after PCS interruption so that degeneration resulting from the subsequent electrolytic mesencephalic lesions could be attributed to interruption of non-cerebellar ascending fibres. The results show that degeneration was present in the thalamus following the electrolyte mesencephalic-diencephalic lesions but it could be accounted for on the basis of damage either to residual PCS fibres, to somatosensory pathways, to intrathalamic connections or to cell groups or projection fibres of the reticular formation, substantia nigra or globus pallidus. It is concluded that there is no direct rubrothalamic projection in the monkey and, in particular, no evidence of a projection from the red nucleus to the ventral lateral or ventral anterior thalamic nuclei. The results also indicate that the mesencephalic reticular formation is the main source of ascending afferents to the nucelus reticularis thalami. Some observations were made concerning nigrostriatal and nigrothalamic projections. Retrograde cell changes resulting from unilateral lesions made caudal to the red nucleus were studied in three animals. The observed cell changes are interpreted as being consistent with the conclusion that there is no rubrothalamic projection.

Age Factors↗

An anatomical study of the projections from the dorsal column nuclei to the midbrain in cat.

The termination of the fibers from the dorsal column nuclei (DCN) to the midbrain has been investigated in the cat with the degeneration method, the anterograde horseradish peroxidase (HRP) method and autoradiography after 3H-leucine injections. The results show that the DCN project to several midbrain regions. The external nucleus of the inferior colliculus (IX) receives the heaviest projection from both the gracile and cuneate nuclei. The DCN fibers form three joint terminal zones in IX. Each terminal zone contains clusters with dense aggregations of DCN fibers. Fairly dense terminal networks are found in the posterior pretectal nucleus (PP) and the compact part of the anterior pretectal nucleus (PAc) as well. More scattered DCN fibers are present in the cuneiform nucleus (CF), the lateral part of the periaqueductal gray (PAG1), the red nucleus (NR), the nucleus of the brachium of the inferior colliculus (B), the mesencephalic reticular formation (MRF) and the intermediate and deep layers of the superior colliculus (SI, SP). The projections to all regions are mainly contralateral. Most of the few ipsilateral fibers terminate in IX. A somatotopic organization was seen in IX and NR. The gracile fibers terminate preferentially in the caudal and lateral part of IX and the cuneate ones preferentially in its rostral and medial part. In the red nucleus the gracile fibers terminate ventral to the cuneate ones. In the pretectal region there was a predominance for gracile fibers. There also appeared to be quantitative differences in the projections from various levels of the gracile nucleus, with more midbrain projecting fibers originating in the rostral than in the middle and caudal parts of the nucleus.

Animals↗

Concurrent excitatory and inhibitory effects of high frequency stimulation: an oculomotor study.

OBJECTIVE: To describe a reversible neurological condition resembling a crossed midbrain syndrome resulting from high frequency stimulation (HFS) in the midbrain. METHODS: Postoperative evaluation of quadripolar electrodes implanted in the area of the subthalamic nucleus of 25 patients with Parkinson's disease (PD) successfully treated by HFS. RESULTS: Four of the 25 patients experienced reversible acute diplopia, with dystonic posture and tremor in the contralateral upper limb when the white matter between the red nucleus and the substantia nigra was stimulated. The motor signs resembled those caused by lesions of the red nucleus. The ipsilateral resting eye position was "in and down" (three patients) or "in" (one patient). Enophthalmos was seen. Abduction was impaired and vertical eye movements were limited, but adduction was spared. The movements of the controlateral eye were normal. The ocular signs could be best explained by sustained hyperactivity of the extrinsic oculomotor nerve. Simultaneous tonic contraction of the superior rectus, the inferior rectus, and inferior oblique may cause the enophthalmos and partial limitation of upward and downward eye movements. Antagonist tonic contraction of the ipsilateral medial rectus severely impairs abduction. CONCLUSION: This crossed midbrain syndrome, possibly resulting from simultaneous activation of oculomotor nerve and lesion-like inhibition of the red nucleus suggests that high frequency stimulation has opposite effects on grey and white matter.

Electric Stimulation Therapy↗

Cortical projections to nuclei adjacent to the oculomotor complex in the medial dien-mesencephalic tegmentum in the monkey.

Cortical projections to cell groups surrounding the oculomotor complex were studied by using the retrograde and anterograde capabilities of the horseradish peroxidase (HRP) technique in old and new world monkeys. Fluid HRP injections or transcannular solid polyacrylamide HRP gel implants were made into the oculomotor nucleus (OMN) and adjacent nuclei to label retrogradely corticofugal neurons that project to this region, and cortical HRP gel implants were made in various areas of the frontal lobe to label anterogradely the trajectories and terminations of cortico-paraoculomotor projections and thus to confirm the retrograde findings. Projections to the paraoculomotor cell groups in the medial dien-mesencephalic tegmentum originate almost exclusively from the frontal lobe. Both retrograde and anterograde studies confirmed that the prearcuate cortex in the concavity of the arcuate sulcus, including the frontal eye field, and, to a lesser extent, suprarcuate rostral dorsal area 6 cortex and the dorsomedial convexity (area 9), project to the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) in the dorsal region of the prerubral field, nucleus of Darkschewitsch (ND), medial accessory nucleus of Bechterew (NB) and dorsomedial parvocellular red nucleus (dmPRN). The premotor area 6 and motor area 4 cortex, on the other hand, give rise to projections that target a larger portion of the parvocellular red nucleus, extending rostrally into the ventral region of the prerubral field, and a rather intense projection to the ND. The interstitial nucleus of Cajal (IC) was distinguished more by its light, or lack of, projections from the frontal cortex. The inferior parietal lobule (IPL, area 7) which has certain common physiological properties with the frontal eye field (FEF area 8) related to the oculomotor system, lacked retrogradely labeled neurons in all cases where transcannular gel implants into the OMN eliminated the possibility of HRP uptake in the corpus callosum or other structures traversed in needle injections, suggesting that the IPL affects eye movement primarily through its rostrally directed corticocortical associational connections with the FEF. In additional cases, the ND-NB-dmPRN configuration of cells that receives FEF input is shown to project to the inferior olivary complex (i.e., is pre-olivo-cerebellar), whereas riMLF and IC give rise to descending projections in the MLF, which target extraocular muscle motor nuclei, vestibular complex, and spinal cord. The results are discussed in terms of the potential role of the cerebral cortex in eye movement mechanisms.

Animals↗

[3H]-2-deoxyglucose uptake study in mutant dystonic hamsters: abnormalities in discrete brain regions of the motor system.

The genetically dystonic (dtSZ) hamster, an animal model of idiopathic paroxysmal dystonia, displays attacks of generalized twisting movements and abnormal postures of limbs and trunk either spontaneously or in response to mild stress. This experimental model may be helpful to give insights into the pathophysiology of idiopathic dystonia in man. In the present study, the regional uptake of [3H]-2-deoxyglucose (2-DG) was examined in brains (75 brain regions) of dtSZ hamsters during the expression of severe dystonia. 2-DG autoradiography revealed significant changes of 2-DG uptake in discrete brain regions of dtSZ hamsters compared with age-matched, nondystonic control hamsters. In dystonic hamsters, a dramatic increase of 2-DG uptake was observed in the red nucleus (159% over control). Furthermore, enhanced 2-DG uptake was found in the ventromedial, ventrolateral, and anteroventral nuclei of the thalamus (19-42%) and in the medial vestibular nucleus (23%). A significant decrease in 2-DG uptake in deep cerebellar nuclei (-30%) may be the result of decreased synaptic activity of GABAergic neurons within these structures resulting in enhanced excitatory output to red nucleus, thalamic, and vestibular nuclei. In dtSZ hamsters, the 2-DG uptake was not significantly altered overall within the basal ganglia. Significant increases of 14% were, however, found in discrete parts of the caudate putamen in which recent studies revealed changes of dopamine receptors. Altered neural activity within the basal ganglia may therefore contribute to increased 2-DG uptake in the ventral thalamic nuclei as well as to decreased 2-DG uptake (-13%) found in the reticular thalamic nucleus. Although the present data are in line with the concept that abnormal thalamocortical activity seems to be critically involved in the dystonic syndrome, altered activities in other motor areas than output structures of the basal ganglia, such as in the red nucleus, may contribute to clinical manifestation of dystonia in mutant hamsters.

Animals↗

Neurotrophic factors prevent the death of CNS neurons after spinal cord lesions in newborn rats.

The aim of this study was to determine if the exogenous administration of neurotrophic factors can rescue immature axotomized CNS neurons in vivo. After spinal cord hemisection in newborn rats, the exogenous administration of neurotrophic factors brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3) and nerve growth factor (NGF), prevents the retrograde cell death of axotomized red nucleus neurons (and other brain stem spinal neurons) in vivo. Rescue of red nucleus neurons was maintained in the presence of BDNF, but only transiently maintained by NT-3 and NGF. Neurons within the nucleus dorsalis (Clarke's nucleus) of the spinal cord are also axotomized by this lesion. The application of exogenous NT-3, but not NGF or BDNF, rescued Clarke's nucleus neurons. These observations indicate that neurotrophic factors play a crucial role in the survival of CNS neurons in vivo during development and after injury. Furthermore, these results indicate that particular populations of neurons are dependent upon specific neurotrophic support after injury.

Animals↗

Regional differences between the immunohistochemical distribution of Ca2+/calmodulin-dependent protein kinase II alpha and beta isoforms in the brainstem of the rat.

The distribution of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) alpha and beta isoforms in the brainstem of adult rats was investigated using an immunohistochemical method with two monoclonal antibodies which specifically recognize the alpha and beta isoform, respectively. We found that these isoforms were differentially expressed by neurons in the substantia nigra, red nucleus, dorsal cochlear nucleus, pontine nuclei and inferior olivary nucleus. Neurons in the inferior olivary nucleus express the alpha isoform, but not the beta isoform. In contrast, neurons in the substantia nigra, red nucleus and pontine nuclei were immunostained with the beta antibody, but not with the alpha antibody. In the dorsal cochlear nucleus, neurons in layers I and II were alpha-immunopositive, whereas neurons in layers III and IV were beta-immunopositive. Therefore, the distribution of the CaM kinase II alpha-immunopositive neurons is completely different from that of CaM kinase II beta-immunopositive neurons. Next we examined the possible coexistence of CaM kinase II alpha isoform and glutamate or that of CaM kinase II beta isoform and glutamic acid decarboxylase (GAD) in the single neuron by double immunofluorescence labelling using a pair of anti-alpha and anti-glutamate antibodies, or a pair of anti-beta and anti-GAD antibodies. The results indicated that neurons expressing anti-alpha immunoreactivity were also immunopositive against anti-glutamate antibody, and neurons expressing beta isoform were also immunopositive against anti-GAD antibody, suggesting that alpha-immunopositive neurons are classified as excitatory-type neurons, and on the contrary, beta-immunopositive neurons are classified as inhibitory-type neurons. In conclusion, the present study confirmed that alpha- and beta-isoforms of CaM kinase II are differentially expressed in the nuclei of the brainstem and have different roles.

Animals↗

Sources of descending afferents to the inferior olive from the upper brain stem in the cat as revealed by the retrograde transport of horseradish peroxidase.

The retrograde transport of horseradish peroxidase (HRP) was employed in 35 cats to trace the sources of descending afferents to the inferior olivary nucleus. The majority of HRP-labeled cells were located in the ipsilateral mesencephalon, from the rostral pole of the red nucleus to the caudomedial border of the thalamus. Among the heavily labeled nuclear groups were the the parvocellular red nucleus, the interstitial nucleus of Cajal, the nucleus of Darkschewitsch, and the caudomedial extremity of the subparafascicular nucleus. Occasional cells were also labeled in the reticular formation lateral to the interstitial nucleus of Cajal in the caudomedial parafascicular nucleus, in the nucleus of the fields of Forel, and in the central gray. It was not possible to recognize a topographic distribution of the labeled cells corresponding to the localization of the HRP deposits. Elsewhere in the midbrain, there were HRP-labeled cells in the deep layers of the superior colliculus (IV and VI), predominantly on the side contralateral to the injection and in the nucleus of the optic tract, and in the anterior and posterior pretectal nuclei, ipsilaterally. These groups were best labeled after caudally located injections in the olive. Certain areas previously reported to project to the inferior olive were devoid of labeled cells; these included the basal ganglia, the rostral raphe nuclei, and the nucleus of Edinger-Westphal. It appears that the mesencephalic nuclei bordering the central gray represent the major source of descending afferents to the olive.

Animals↗

Fusimotor effects of midbrain stimulation on jaw muscle spindles of the anaesthetized cat.

The effects of electrical stimulation within the midbrain on fusimotor output to the jaw elevator muscles were studied in anaesthetized cats. Muscle spindle afferents recorded in the mesencephalic trigeminal nucleus were categorised as primary or secondary by their responses to succinylcholine during sinusoidal or ramp-and-hold stretches. Changes in their stretch responses during midbrain stimulation were then assessed by changes in bias and in dynamic sensitivity. Problems were encountered in interpreting changes in sine wave stretch responses of primary afferents, in some of which a very small change in firing pattern produced large changes in estimates of the response amplitude. Sine wave testing also sometimes over-estimated static effects and under-estimated dynamic effects relative to ramp responses. On other occasions a small amount of static fusimotor activity caused a marked increase in sine response amplitude, which could be wrongly interpreted as a dynamic effect. Consequently, ramp responses only were used for diagnosing fusimotor changes. The most effective region for producing pure dynamic fusimotor excitation was directly rostral to the red nucleus, extending dorsally and ventrally approximately in the course of the retroflex bundle. Stimulation of regions caudal and dorso-caudal to the red nucleus, previously designated as the mesencephalic area for dynamic fusimotor control of leg muscles, gave static or mixed static and dynamic effects on jaw spindles. The use of midbrain stimulation to identify fusimotor neurones of jaw muscles as static or dynamic would be most reliable with stimulation just rostral to the red nucleus and would require spindle afferent behaviour to be monitored at the same time with ramp stretches.

Anesthesia↗