Somatoiopic studies on cerebellar fastigial cells

Summary The somatotopic inputs into fastigial cells have been studied in relation to cutaneous mechanoreceptors of forelimb and hindlimb. Some fastigial cells were very discriminative, not only in respect of the limb, but also to restricted areas of hairy skin and related toe pads. Others were much less so, forelimb and hindlimb cutaneous receptors evoking similar excitatory-inhibitory responses. In addition, from the contralateral hindlimb, responses were evoked which were comparable with those from the ipsilateral limb.Somatotopic diagrams have been constructed which show in four experiments the sites of fastigial cells in the parasagittal plane of the microelectrode tracks. For each experiment four separate plottings give a comparison of the sizes of responses evoked for forelimb and hindlimb: excitation from nerve volleys; inhibition from nerve volleys; excitation from pad taps; inhibition from pad taps. In this way it is shown that fastigial cells with similar somatotopic relations often occur in clusters, particularly when assessed by their inhibitory responses.Since fastigial inhibition is largely due to Purkyn cells, there is an attempt to correlate the somatotopic relations of Purkyn cells with the somatotopy of fastigial cell inhibition. The excitation of fastigial cells exhibits less somatotopic discrimination, which conforms with the poor somatotopic discrimination of cells of the lateral reticular nucleus.In a final discussion there is consideration of two principal projections from the vermis of the anterior lobe: Purkyn cells inhibiting Deiters neur; Purkyn cells inhibiting fastigial cells which in turn monosynaptically excite Deiters neurones, the inhibition of Deiters neurones being then by disfacilitation. The degree of forelimb-hindlimb convergence in these pathways is reconsidered and is diagrammatically illustrated.     

Responses of the cerebellar fastigial neurones to tilt

Summary The activity of units located in the rostral portion of the fastigial nucleus has been recorded in decerebrate, unanaesthetized cats in response to tilt. The responses consisted of steady variation of the discharge rates when the animal was tilted in the median plane. The majority of the units exhibited a frequency increase on ipsilateral tilt and a frequency decrease on contralateral tilt. Some units displayed an opposite type of response, while some others responded with a frequency increase on tilt in both directions. It was possible to establish a relationship between the amount of the response and the degree of tilt. Some units exhibited a dynamic response during the movement of the tilt table and the amount of this dynamic response was related to the velocity of the movement. It was not possible to demonstrate a convergence of macular input on these dynamic units. The responses did not depend on proprioceptive feed-back since they persisted after deep curarization of the animal. Since the rostro-fastigial neurones project on the dorsal ipsilateral Deiters' nucleus the existence of a cerebellar fastigial loop through which macular information may reach Deiters' nucleus has been postulated. This loop may be of relevance in the cerebellar and vestibular control of postural activities.This investigation was supported by Public Health Service Research Grant NS 07685-05 from the National Institute of Neurological Diseases and Blindness, N.I.H., Public Health Service, U.S.A. and by a Research Grant from the Consiglio Nazionale delle Ricerche, Italy.     

Responses of neurones in the brainstem raphe nuclei to stimulation of the cerebellar fastigial nuclei in the cat

Stimulation of the fastigial nuclei of the cerebellum was found to excite units located throughout the raphe nuclei of the brainstem. Raphe spinal units with axons conducting at velocities below 20 m/s were either unaffected by fastigial nucleus stimulation or inconsistently excited at long latency. In contrast units with faster conducting spinal axons throughout the raphe and more dorsally in the reticular formation were excited by stimulation of the fastigial nuclei. Many of these units responded at short latency and followed high rates of repetitive stimulation.     

Effects on gastric motility from the cerebellar fastigial nucleus.

In acute experiments on chloralosed cats gastric motility, blood pressure and heart rate were investigated for influences exerted by the fastigial nucleus. Besides pressor responses, fastigial stimulation could produce either gastric excitation or relaxation and the background of these responses was analysed by selective nerve sectioning and administration of suitable autonomic blocking agents. Suppression of prevailing gastric motility was found to be mediated mainly by increased discharge in adrenergic nerve fibres but also by adrenal catecholamine release. -- Gastric excitation could be induced in three different ways, first via increased activity in vagal cholinergic fibres, second, by fastigial suppression of the vago-vagal non-adrenergic relaxatory reflex. In addition, when laparotomy or other noxious abdominal stimuli had induced inhibitory gastric reflexes, the consequent sympathetic discharge could be suppressed by fastigial stimulation resulting in enhanced gastric motility. -- The importance of background activity in the various nervous pathways for the fastigially induced gastric responses is discussed.     

The central inhibitory effect of interleukin-1 on gastric acid secretion

The effect of interleukin-1 (IL-1) on gastric secretory functions was examined in pylorus-ligated conscious rats. Intracisternal (i.c.) injection of IL-1 beta (1-100 ng) induced dose-related, long-lasting inhibition of gastric acid output, which was due to the reductions of both the amount and the acid concentration of the gastric juice. A much higher dose of IL-1 alpha was required to achieve identical effects on gastric acid secretion when it was given by intravenous routes. The i.c. injection of IL-1 alpha also had an inhibition of gastric secretion. This inhibitory effect of i.c. applied IL-1 beta on gastric acid secretion was completely abolished in indomethacin-pretreated animals but not in reserpine-pretreated ones. These results suggest that IL-1 may have an inhibitory action on the regulation of gastric secretory functions by its central action which is dependent on the eicosanoid metabolism.     

Electrical stimulation of cerebellar fastigial nucleus fails to rematch blood flow and metabolism in focal ischemic infarctions

Electrical stimulation of the cerebellar fastigial nucleus (FN) in rat (1 h) reduces, by 50%, the infarction produced by occlusion of the middle cerebral artery (MCAO). We investigated whether salvage was associated with elevations in regional cerebral blood flow (rCBF) and/or reductions of regional cerebral glucose utilization (rCGU) in the retrievable zone (RZ). rCGU and rCBF were measured autoradiographically 1 h after MCAO. MCAO reduced rCBF to < 15% in the irretrievable zone (IZ) and 50% in the RZ (P < 0.01 for each) while FN stimulation alone globally elevated rCBF by 60% (P < 0.01). rCGU was not changed. After MCAO, FN stimulation failed to increase the reduced rCBF but elevated rCGU globally (to 30%). Reductions of focal ischemic infarctions by stimulating FN cannot be attributed to changes in rCBF and or rCGU.     

Responses of cerebellar fastigial neurons to single muscle activation

Summary In lightly barbiturized cats, the discharges of neurons in the cerebellar fastigial nucleus (CBM) were recorded while single muscles in ipsilateral forelimb were activated by direct stimulation. The aim was a) to verify whether CBM cells could selectively detect the activity of afferent fibers from a muscle or a joint and b) to compare the various response characteristics of the rostral and the caudal division of the nucleus, which are known to control a different muscular periphery. Six muscles were routinely tested, two axial, two proximal and two distal ones. A good percentage of neurons in both partitions of the nucleus responded to the muscles tested (53% and 48% in the rostral and caudal part, respectively). In the rostral part of CBM a large proportion of cells (78% of those responsive) were influenced by one or more muscles having either the same function (the extensors or flexors) or acting on the same joint. Many such neurons showed a marked capability to respond to activation of distal muscles and a prevalence of inhibitory responses mainly on contraction of extensor and axial muscles. In the caudal division of the nucleus, 47% of the responsive cells displayed a stereotyped discharge pattern (excitatory or inhibitory) in response to activation of any tested muscle. In contrast to the rostral CBM the incidence of responses to proximal and distal muscles was about equal in the caudal CBM and a majority of neurons had excitatory responses to flexor muscle contraction. The latencies of the excitatory effects ranged from 8 to 53 ms in rostral and 9 up to 69 ms in caudal CBM. Inhibitory responses were seen at latencies between 9–78 ms in rostral and 9–80 ms in the caudal parts of the nucleus, the distribution in the latter being bimodal. The high specificity of the responses observed in rostral CBM to the activation of ipsilateral forelimb muscles is consistent with the suggestion that the nuclear output influences the same peripheral area. The conspicuous number of neurons with inhibitory responses detected on contractions of axial and extensor muscles could possibly be due to an inhibitory feedback from the peripheral muscles to the rostral CBM division. With regards to the caudal part of the nucleus, which is known to facilitate contralateral extensor muscles, the excitatory effects seen on ipsilateral flexor muscle activation could support a mechanism of postural balance.     

A comparison of the response characteristics of cerebellar fastigial and vermal cortex neurons to sinusoidal stimulation of macular vestibular receptors

1. The responses of neurons located in the rostral part of the fastigial nucleus to sinusoidal tilt of the animal were recorded in precollicular decerebrate cats and compared with those elicited by the same stimulation in Purkinje (P) cells located in the vermal cortex of the cerebellar anterior lobe. In particular, by fixing the head and the body of the animal to the tilting table and by rotating the animal around its longitudinal axis, it was possible to elicit a selective labyrinth input without eliciting a neck input.
2. Among the 60 fastigial neurons tested, 43 units responded to sinusoidal tilt at the frequency of 0.026 Hz and at the peak amplitude of displacement of 10°–15°. On the other hand, among 106 P-cells tested for a mossy fiber (MF) response to the labyrinth input, 32 units were affected by the same parameters of stimulation. In both instances the response consisted in a periodic modulation of the discharge frequency, which was related to the position of the animal. Most of the responses of the fastigial units to the labyrinth input were characterized by a peak excitation in phase with side-down tilt of the animal and by inhibition during side-up tilt, whereas most of the MF-responses of the P-cells to the labyrinth input showed just the opposite behavior.
3. The threshold amplitude of tilt responsible for these responses varied in different units from 1° to 3° at the frequency of 0.026 Hz. The sensitivity of the first harmonic of the unit responses to tilt, expressed in percentage change of the average firing rate per degree of displacement, corresponded on the average to 1.73±1.16, S.D., for the fastigal neurons and to 1.61±0.94, S.D., for the P-cells. These values did not change or were only slightly modified as a result of increasing amplitude of stimulation from 1°–3° to 15°–25° at a frequency of 0.026 Hz. Moreover, changes in amplitude of stimulation at the parameters reported above did not greatly modify the phase angle of the first harmonic of the responses relative to the side-down position of the animal. Units located in the medial corticonuclear zone of the cerebellum did not show any change in sensitivity and phase angle of the responses by increasing the frequency of tilt from 0.015 to 0.20 Hz at the fixed amplitude of 10°–15°, thus indicating that these responses depended upon stimulation of macular receptors. In other units, however, these changes in frequency of rotation modified the phase angle of the responses, which became related to velocity rather than to the positional signal, due to stimulation of semicircular canal receptors.
4. The observation that most of the responsive fastigial neurons increased their firing rate, while most of the responding P-cells located in the vermal cortex of the cerebellar anterior lobe decreased their firing rate during side-down rotation of the animal is discussed in relation to the postural changes of the limbs elicited during asymmetric stimulation of macular receptors.

     

Attenuation of septal hyperemotionality by cerebellar fastigial lesions in the rat

Lesions of the cerebellar fastigial nucleus were found to greatly attenuate the hyperemotionality produced by simultaneous septal lesions in the rat. Lesions dorsal or lateral to the fastigial nucleus had no effect. This lesion-related attenuation of emotionality produced by fastigial destruction appeared quite specific. Other motivated behaviors such as food intake and activity were not affected. Further, the characteristic increase in social contacts seen after septal destruction was not altered by the fastigial lesions. The results support the view that the cerebellar fastigial nucleus is part of a complex limbic-brainstem network involved in the control of emotional and motivational behaviors.     

Effect of lesions of cerebellar fastigial nuclei on lymphocyte functions of rats

The cerebellum, probably owing to its traditional concept limited to motor control, is less well studied in immunoregulation. To obtain more comprehension and knowledge on cerebellar functions, we investigated effect of cerebellar fastigial nucleus (FN), an output nucleus of the spinocerebellum, on lymphocyte functions, and explored central and peripheral pathways involved in the effect. Kainic acid (KA) was microinjected into bilateral FN of rats (0.4 microg KA in 0.4 microl saline for each side) to destroy neurons of the nuclei. On days 8, 16 and 32 following the FN lesions, methyl-thiazole-tetrazolium (MTT) assay and flow cytometry were used to measure proliferation of concanavalin A (Con A)-induced lymphocytes and cytotoxicity of natural killer (NK) cells against YAC-1 cells, respectively. Meanwhile, glutamate and monoamine neurotransmitters, including norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT), in the hypothalamus and the spleen were determined by means of high-performance liquid chromatography (HPLC) assay. Adrenocorticotropic hormone (ACTH) and cortisol in the plasma were also detected respectively by radioimmunoassay and chemiluminescent immunoassay after the FN lesions. We found that the Con A-induced lymphocyte proliferation and the NK cell cytotoxicity were both significantly enhanced on days 8, 16 and 32 following the effective lesions of the bilateral FN in comparison with those of matching control rats microinjected with saline in their FN. Contents of glutamate and NE, not DA and 5-HT, in the hypothalamus, and concentration of NE, not DA, in the spleen were all remarkably reduced on the 16th day following the FN lesions, when both the T lymphocyte proliferation and the NK cell cytotoxicity were dramatically increased. However, levels of ACTH and cortisol in the plasma had no notable differences between FN lesion rats and FN saline ones when the enhanced T and NK cell functions occurred. These findings reveal that the cerebellar FN participates in the modulation of lymphocyte functions and that the hypothalamus and sympathetic nerves innervating lymphoid organs are involved in this neuroimmunomodulation. Thus, a possible central and peripheral pathway for the spinocerebellum to regulate lymphocyte functions is suggested, i.e. cerebellum-hypothalamus-sympathetic nerves-lymphocytes, while the functional axis of hypothalamus-pituitary-adrenal gland may not contribute to mediation of the spinocerebellar immunomodulation.     

Excitation of histamine on neuronal activity of cerebellar fastigial nucleus in rat

Inflammation Research -     

Influences on colonic and small intestinal motility by the cerebellar fastigial nucleus.

The fastigial influence on intestinal motility was investigated in acute experiments on chloralosed cats. Motility was recorded both from the small and large intestine. Electrical stimulation of the rostral fastigial pole produced, in combination with a blood pressure rise, increased motor activity in ileum and colon while jejunum could respond with either increased on decreased motility. The intestinal responses were neither secondary to changes in intestinal blood flow, nor to baroreceptor reflexes induced by the increased blood pressure. The excitatory responses were not due to increased parasympathetic activity since sectioning of such pathways failed to abolish the responses. Instead, interruption of adrenergic sympathetic discharge, accomplished either by guanethidine or by sectioning of relevant nerves, aid eliminate the responses, indicating that the fastigial effects were mediated by suppression of prevailing adrenergic tone. Noxious stimuli to the abdomen, including laparotomy, inhibit intestinal motility by a reflex increase in adrenergic discharge. It is suggested that fastigial influence on intestinal motility is mainly due to suppression of this reflex.     

Kinetics of the inhibitory effect of flavonoids on histamine secretion from mast cells

The effect of cromoglycate and of natural flavonoids on histamine release from peritoneal rat mast cells induced by compound 48/80 and ionophore A23187 was studied according to preincubation time of mast cells with drugs and to incubation time of cells with the triggering agent. Preincubation of cells with cromoglycate, dihydroquercetin and amentoflavone, a biflavonoid, decreased the potency of drugs to inhibit the ionophore-induced release; the optimal inhibitions were observed when drugs were added simultaneously with the ionophore A23187. In contrast, a short preincubation (2 min) of cells with quercetin or luteolin decreased their inhibitory effect on the ionophore-induced release, whereas a longer preincubation increased the inhibition. When compound 48/80 was used to trigger histamine secretion, the inhibitory potencies of all the compounds used were decreased according to preincubation time. Dihydroquercetin (taxifolin), previously considered as inactive, showed an interesting cromoglycate-like behaviour.