Acta physiol. scand. 1975. 94. 95-104 From the Department of Physiology, University of Goteborg, Sweden
Influences on the Defecation and Micturition Reflexes by the Cerebellar Fastigial Nucleus BY
JAN MARTNER Received 16 December 1974
Abstract MARTNER, J. Influences of the defecation and micturition reflexes by the cerebellar fastigial nucleus. Acta physiol. scand. 1975. 94. 95-104. The influence of the cerebellar fastigial nucleus on the defecation and micturition reflexes was investigated in chloralosed cats with recordings of colonic blood flow and motility, intravesical and intraabdominal pressures. Whenever effective, topical fastigial stimulation regularly suppressed both somatomotor and autonomic components of the defecation reflex, to the extent that the straining movements as well as the colonic vasodilatator and motor responses associated with defecation could be completely inhibited. Bladder motility could either be suppressed or enhanced, depending both on prevailing bladder tone and on the fastigial site stimulated. The autonomically conveyed inhibitory responses were in both cases independent of the adrenergic sympathetic pathways, since they were unaffected both by sympathetic nerve sectioning and by adrenergic blocking drugs but eliminated by pelvic nerve section. It is suggested that the mentioned fastigial inhibitory influences are exerted on the spinal parasympathetic reflexes controlling the bladder and colon. Parallels between fastigial control of autonomic and somatomotor mechanisms are discussed.
Increasing evidence is accumulating in support of a role for the cerebellum also in autonomic control. Especially interesting in this context is the fastigial nucleus which is very potent in eliciting both cardiovascular (Achari and Downman 1969, Miura and Reis 1969) and gastrointestinal responses (Lisander and Martner 1974) upon electrical stimulation. Both types of responses are induced from the rostra1 ventromedial fastigial pole and involve predominantly a modulation of adrenergic sympathetic discharge, which is enhanced to the circulatory system but as has been recently shown is generally suppressed to the colon and the small intestine (Martner 1975). It was considered of interest to investigate whether also parasympathetically conveyed autonomic responses can be directly influenced from the fastigial nucleus, where especially the defecation and micturition reflexes are of relevance. To fully reveal the fastigial influence on the parasympathetically induced colonic motor responses during defecation, it was necessary to eliminate direct fastigial adrenergic modulation of the colon (Martner 1975). A possible fastigial influence on the defecation reflex is of particular interest also from another point of view, insofar as it involves easily elicited somatomotor and autonomic components. The former requires for its full expression supraspinal levels while the latter 95
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is basically conveyed at spinal sacral levels (Garry 1933) though being considerably influenced also by bulbar and suprabulbar autonomic centres (Hatcher and Weiss 1923, Koppanyi 1930, Hess and Brugger 1943). While the cerebellar control of somatomotor mechanisms is by now fairly well understood, comparatively little is known about the principles of cerebellar autonomic control. Therefore, investigations of cerebellar effects on reflexes that involve both somatomotor and autonomic components might help to elucidate how the cerebellum influences autonomic mechanisms. For such reasons, the first part of the present study deals with the fastigial influences of the somatomotor and autonomic components of the defecation reflex. Concerning the urinary bladder, several authors have reported cerebellar excitatory as well as inhibitory influences, especially from the vermal cortex (Whiteside and Guyton 1952, Emerson et al. 1961, Bruhn et al. 1961, Rasheed, Manchanda and Anand 1970). Also from the fastigial nucleus both micturition (Chambers 1947) and suppression of the micturition reflex (Bradley and Teague 1969) can be elicited and bladder tone can be either increased or decreased (Bellar and Talan 1971, Manchanda and Bhattarai 1972, Lisander and Martner 1974). To further characterize the fastigial structures influencing autonomic mechanisms it was considered of interest to investigate whether they influence also bladder motility in a more regular and specific way. A brief preliminary report covering part of the present results has earlier been presented (Lisander and Martner 1974).
Methods Experiments were performed on 30 cats, anesthetized by chloralose, 50-60 mg/kg b.wt. Free airways were secured by a tracheal cannula. Srimulurions. For cerebellar stimulation the Horsley-Clarke technique was utilized, exploring the fastigial nucleus by electrodes inserted perpendicularly to the horizontal plane. Stimulation was performed via thin monopolar stainless steel electrodes, insulated except for the tip (about 50-100 p m in diameter), using square wave pulses of 1 ms from a constant current stimulator. The intensities used were varied between 0.03 and 0.3 mA (corresponding to a voltage range from 1 to 3.5 V) at a frequency range of 10 to 50 Hz. After each experiment a small lesion was induced around the electrode tip by an anodal current of 1 mA for 10 s. The head of the animal was then perfused by saline followed by a 10% solution of formaldehyde, relevant cerebellar parts were frozen sectioned and the stimulation points identified. Recordings. Arterial pressure was recorded through a femoral catheter connected to a Statham P 23 A C transducer, writing on a Grass polygraph. Heart rate was measured by connecting the pressure recording amplifier to a Grass Tachograph unit. When bladder pressure was recorded, the abdominal wall overlying the urethra was opened by a small incision and a catheter inserted into the bladder via the urethra. Variations in intravesical pressure, reflecting bladder motility, were then recorded by connecting the catheter to a transducer. A saline reservoir, adjustable to various levels, was connected to the catheter via a side branch, thus allowing for bladder filling at different pressures. Sometimes the abdominal incision was extended so that the hypogastric and pelvic nerves could be isolated, placed on ligatures and cut in the course of the experiment. The defecation reflex was elicited either by afferent stimulation of one cut pelvic nerve, the other being left intact, o r by applying a mechanical frictional stimulation to the rectal mucosa (cf. Hulten 1969). For recording colonic motility and blood flow the abdominal wall was opened by a midline incision and the small intestine was extirpated together with the spleen and greater omentum. About 5 cm of the most proximal colonic loop was isolated, gently rinsed from contents and filled with Tyrode solution. The loop was distally isolated by loose ligatures to avoid damage of the intramural nervous connections. Colonic motility was recorded as intraluminal volume changes, transmitted via a wide tube to a container with a diameter of 5 cm mounted on a Grass force displacement transducer FTO 3, thus continuously recording the weight of the container. The level of the container was adjusted to obtain an intraluminal
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Fig. 1. Cat 3.0 kg. Adrenergic fibres blocked by guanethidine, 4 mg/kg. Mechanical rectal stimulation elicits powerful colonic contractions superimposed o n spontaneous motility. Note that a concomitant fastigial stimulation (50 Hz, 1 ms, 0.04 mA) completely abolishes the colonic motor responses.
pressure of 5-10 cm H,O. Colonic blood flow was determined in heparinized animals by recording the venous outflow from the superior mesenteric vein after extirpation of the small intestine. After passing a closed optical drop recorder, operating an ordinate writer, the blood was returned to the animal via the femoral vein. Drugs. Since respiratory movements sometimes interfered with the colonic events, gallamine iodide (FlaxediP) 4 mg/kg b.wt. i.v. was in these cases given to avoid such disturbances, whereupon artificial respiration was given. N o muscle paralysing drugs were, however, given, when the straining movements in connection with defecation were to be recorded, these were registered as pressure increases in an intraabdominal balloon. In most experiments the secretion from the adrenals was eliminated by encircling ligatures around both glands and adrenocortical substitution was then given by i.v. injection of hydrocortisone (Solu-Gluc@, Erco) 10 mgjkg b.wt. In some experiments the lumbar colonic nerves were dissected free from the inferior mesenteric artery and cut distally to the ganglion but in most cases the adrenergic supply to the colon was instead blocked by guanethidine (Ismelin@,CIBA) 4 mg/kg b.wt. i.v., sometimes in combination with dibenzyline (Smith, Kline and French) 4 mg/kg b.wt. i.v. As an ablocking agent phentolamine (Regitin@,CIBA, 1 mg/kg b.wt. i.v.) was also used. /?'-blockade was induced by propranolol (Inderala, ICI) 0.5-1 mg/kg b.wt. i.v. Atropine (atropine sulphate) was used in a dose of 0.5-1 mg/kg b.wt. i.v.
Results 1. Fastigial influence on defecation Defecationinvolves activation of both somatomotor and autonomic reflexarcs, wherestraining movements increase the intraabdominal pressure and, together with colonic contractions, help to expel the faeces. Colonic vasodilatation also forms part of the pattern (HultCn 1969). All these reflexly induced changes were found to be influenced by fastigial stimulation. As illustrated in Fig. 1, the reflex colonic contractions elicited by mechanical rectal stimulation could be completely suppressed in the adrenergically blocked animals. This was the case in 7 cats and only in 2 expts. fastigial stimulation failed to attenuate the colonic response. Likewise, reflex colonic contractions induced by afferent pelvic nerve stimulation were inhibited as well ( 2 cats). Atropine reduced but did not eliminate the reflex colonic contractions and the small remaining reflex motor responses to rectal stimulation were also suppressed by fastigial stimulation. Fig. 2 shows that the straining movements, reflexly induced by afferent pelvic nerve stimulation, could be completely suppressed by fastigial stimulations. Mechanical rectal 7 - 755875
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200 ARTERIAL BLOOD PRESSURE, m m Hg loo
TIME, I rnin FASTIGIAL STIM. AFFERENT PELVIC NERVE STIM.
Fig. 2. Cat 2.0 kg. The lumbar colonic nerves and left pelvic nerve cut. Afferent pelvic nerve stimulation induces straining movements recorded as intermittent increases in intraabdominal pressure. Note that fastigial stimulation (50 Hz, 1 ms, 0.2 mA) completely blocks the somatomotor straining movements.
stimulation in one cat elicited reproducible straining movements and they, too, were inhibited by fastigial stimulation. In 3 expts. colonic blood flow was recorded in order to explore the fastigial influence on the colonic vasodilatation accompanying the defecation reflex. Fig. 3 shows such a sequence, intentionally chosen late in the experiment when the colon, perhaps due to deterioration, no longer exhibited any appreciable motor responses that could mechanically interfere with the reflex vasodilatation. Also this latter response could be completely suppressed by fastigial stimulation which, in itself, did not influence colonic blood flow in the adrenergically blocked animal. This was the case in all 3 expts. where a reflex vasodilator response could be repeatedly elicited, whether by means of afferent pelvic nerve stimulation or by mechanical rectal stimulation. In no case did any facilitation of the components comprising the defecation reflex occur. The responsive fastigial area corresponded well with that from which sympathetically mediated blood pressure rises are elicited and was located in the ventromedial part of the rostra1 fastigial pole. For reasons discussed below most animals were adrenergically blocked after that the fastigial pressor area had been identified. Fig. 6, right side of each drawing, summarizes the localization of the points effective in suppressing the defecation reflex, the different components of which seem to be intermingled and coinciding with the fastigial pressor area.
2. Fustigiul influence on bladder motility Filling the bladder with saline regularly induced spontaneous contractions which could markedly raise intravesical pressure. If the bladder outlet was occluded, this increased bladder pressure was sustained enough as to allow an exploration whether, and in which direction, it was affected by cerebellar stimulation. Total bladder inhibition as a result of fastigial stimulation was observed in all 17 cats tested in this way. As shown in Fig. 4 the suppression of bladder motility was prompt and maintained throughout the fastigial stimulation. However, inhibitory bladder responses could be elicited also from fastigial structures outside the fastigial pressor area, which is evident from panel A where the first stimulation
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Fig. 3. Cat 3.3 kg. The adrenergic fibres blocked by a combination of guanethidine 4 mg/kg b.wt., and dibenzyline, 4 mgjkg b.wt. Mechanical rectal stimulation induces reflex colonic vasodilatation which is independent of motility changes. Note that fastigial stimulation (50 Hz, 1 ms, 0.1 mA) totally abolishes this reflex vasodilatation while fastigial stimulation p e r se has no effect on colonic blood flow.
was performed with the electrode placed 1.5 mm dorsally to the pressor area. The electrode was then lowered 1.5 mm (second stimulation, panel A) into the pressor area and still bladder inhibition was obtained. If the bladder contraction was allowed to spontaneously subside and fastigial stimulation was again repeated a small "rebound" bladder contraction was occasionally observed upon cessation of the stimulation. The fastigial suppression of bladder motility was not due to activation of sympathetic adrenergic fibres since neither guanethidine (4 mg/kg b.wt.) nor a combination of a- and /3-adrenergic blocking agents (phentolamine 1 mg/kg b.wt. and propranolol 1 mg/kg b.wt.) could abolish the fastigial responses (Fig. 4, panel B). Moreover, sectioning of the sympathetic hypogastric nerves to the bladder did not influence the fastigial inhibitory responses. Cutting the pelvic nerves eliminated reflexly induced bladder contraction and no inhibitory A
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Fig. 4. Cat 3.0 kg. Effect on bladder motility by fastigial stimulation (50 Hz, 1 rns, 0.1 mA). Inhibition of reflexly induced bladder contraction can he accomplished from cerebellar sites both above and within the fastigial pressor area (first and second stimulation, panel A). Complete adrenergic blockade with guanethidine 4 mg/kg b.wt., phentolamine 1 mg/kg b.wt. and propranolol 1 mg/kg b.wt. does not abolish the inhibitory effect of fastigial stimulation (panel B).
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Fig. 5. Cat 2.8 kg. Fastigial stimulation (50 Hz, 1 ms, 0.1 mA) induces inhibition of bladder motility when performed against a background of high, sustained intravesical pressure (panel A). The same fastigial site elicits bladder contraction if stimulation is performed during a background of low bladder tone. The small oscillations in bladder pressure seen during bladder inhibition are due to respiratory movernents.
fastigial influence could now be traced. Atropine (1 mg/kg b.wt.) substantially reduced the reflex bladder contractions but fastigial stimulation suppressed also the small remaining contraction waves. Bladder contractions could also result upon fastigial stimulation although they were not so easily demonstrated as were the bladder inhibitions. However, once appearing they could be quite prominent (Fig. 5, panel B). This figure further illustrates that the very same fastigial point, from which excitatory responses could be elicited (panel B), could also depress bladder motility, once a pronounced and sustained reflex bladder tone was at hand (panel A). Neither the excitatory nor the inhibitory bladder response were strictly confined to the fastigial pressor area although the former type of response was usually associated with the pressor response. The left side of Fig. 6 summarizes the points from which bladder responses were elicited. The fastigial nucleus can evidently not be divided into one excitatory and one inhibitory area in this very respect, even though the bladder inhibitory responses (open triangles) tend to cover a larger area. Contrary to most other fastigial autonomic effects, including bladder excitation, the inhibitory bladder response seems to follow an “all or nothing law”. Thus, while low stimulation frequencies did not noticeably influence bladder tone, a gradual frequency increase suddenly induced total suppression of bladder contraction, usually when 10-20 Hz were reached. This frequency range corresponds well with that where fastigial influences on e.g. blood pressure and gastrointestinal motility become obvious (Lisander and Martner 1975). However, the latter type of responses, essentially dependent of discharge changes in the sympathetic adrenergic fibres, are characterized by a gradually rising frequency-response curve which reaches a plateau at 40-50 Hz, while the parasympathetically mediated bladder inhibitory responses, once appearing, were then always maximal, i.e. producing 100 per cent suppression of the bladder motility.
FASTIGIAL INFLUENCE ON DEFECATION AND MICTURITION
Fig. 6 . Cerebellar frontal sections, 8 and 8.5 mm posterior to the interaural line. The bladder responses are shown to the left and the defecation responses to the right. Open circles: N o response. Open triangles: Inhibitory bladder responses. Filled triangles: Excitatory bladder responses. Filled dots: Suppression of colonic motor responses. Filled squares: Suppression of colonic vasodilatation. Open squares: Suppression of straining movements. Nf: Nucleus fastigius. Vq: Ventriculus quartus.
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Discussion Colonic motility elicited from the rectum includes profound reflex contractions particularly of the proximal but also of the distal colon (Schmidt and Fulgraff 1963), where both afferent and efferent pathways run in the pelvic nerves (HultCn 1969). The defecation reflex can be elicited either by mechanical rectal stimulation or by pelvic afferent stimulation. In both cases fastigial stimulation could completely abolish the colonic motor response, showing that the fastigial influence cannot be a matter of e.g. any neurogenically conveyed suppression of receptor sensitivity in the rectal mucosa. Hypothalamic stimulation can inhibit spontaneous colonic motility (Wang et al. 1940, Sheehan 1942, Rostad 1973) and the latter investigator found that this inhibitory effect was abolished by adrenergic blockade. In contrast, the fastigially induced suppressions of reflex colonic motility reported here were due to a direct inhibition of the parasympathetically mediated defection reflex and were not a matter of any activation of colonic sympathetic fibres, obvious from the fact that all animals used were subject either to pharmacological adrenergic fibre blockade or to section of the lumbar colonic nerves. This procedure was also necessary for the full expression of the parasympathetically mediated reflex colonic motor and vasodilator responses, which are known to be suppressed by a prevailing sympathetic discharge, presumably at the intramural ganglionic level (HultCn 1969). Moreover, the fastigial influence on spontaneous colonic motility in cats is excitatory in nature and mediated by a suppression of prevailing sympathetic discharge (Lisander and Martner 1974). Elimination of the sympathetic inhibitory influence on parasympathetically mediated colonic responses, which would certainly interfere with the present type of study, was another reason for using various kinds of adrenergic blockade. Ligation of the adrenals excluded the possibility that the fastigial inhibition of the reflex colonic motility was mediated by a release of catecholamines from the adrenal medulla (Lisander and Martner 1973). Besides influencing colonic motor activity, fastigial stimulation could also completely suppress the reflex vasodilatation accompanying defecation. Efferent pelvic nerve stimulation elicits mucosal vasodilatation and secretion (Wright, Florey and Jenning 1938) and HultCn (1969) showed that the vasodilatation forms part of the defecation reflex and is neither eliminated by adrenergic nor by cholinergic blocking agents. Whichever the trans-
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mittor mechanism involved at these parasympathetic nerve endings, the fastigial nucleus could completely suppress this vascular response. Interestingly, the somatomotor component of the defecation reflex was affected by the same fastigial area and in the same inhibitory way as the autonomic components. Thus, total suppression of the straining movements was always induced by fastigial stimulation. Cerebellar modulations of somatomotor mechanisms are wellknown ever since Lowenthal and Horsley (1 897) reported inhibition of decerebrate rigidity by cerebellar stimulation. Since the fastigial nucleus always modified the somatomotor and autonomic components of the defecation reflex in the same direction it seems likely that cerebellar control may be exerted according to similar principles both concerning somatomotor and autonomic mechanisms. In fact, other parallels between the cerebellar influence on somatomotor and autonomic mechanisms d o exist and can be illustrated e.g. by comparing wellknown cerebellar somatomotor effects with the results obtained on bladder autonomic functions. It was found in the present experiments that the fastigial nucleus could both inhibit and augment bladder motility, in consonance with the findings of Beller and Talan (1971) and Manchanda and Bhattarai (1972). Determinant of the direction of the response was both the prevailing bladder tone and the cerebellar site stimulated. Thus, moving the electrode only 0.5 mm sometimes changed an inhibitory response into an excitatory one. Such a reversal could be obtained even from the same fastigial site; inhibitions occurring during periods of reflexly induced bladder contractions, but changing into excitatory responses when the contractions had spontaneously subsided. Similar effects have been induced from the cerebellar cortex (Whiteside and Guyton 1952). The same kind of variable cerebellar influence, depending on background activity, has been illustrated also concerning the cardiovascular system (Moruzzi 1938) and is also demonstrated concerning somatomotor reflexes (Moruzzi 1936). Thus, cerebellar stimulation produced inhibition of extensor hypertonia in decerebrate cats, while increased extensor tone was occasionally recorded if stimulation was undertaken during hypotonia, sometimes as a rebound effect at the end of the stimulation. Such rebound phenomena have been observed both for the autonomic and somatomotor components of the defence reaction during sham rage (Zanchetti and Zoccolini 1954) and were also observed concerning the purely autonomic responses of the bladder in the present study. The finding that cerebellar stimulation produced a constant and generalized inhibition of e . g . the defecation reflex in the present experiments does, however, not necessarily imply that the cerebellum normally always exerts a suppressive influence in these respects. Electrical stimulation of specific brain areas does not necessarily simulate in vivo patterns in a precise way. For example, such stimulations excite, certainly also antidromically and without discrimination, both afferent and efferent pathways and may affect both fibres and neuron somata. Hence, if effects can be demonstrated in the form of fastigial suppression of defecation and micturition, as in this case, it no doubt indicates that the cerebellum is involved in the control of these reflexes but reveals little about the way by which it is normally brought about, whether concerning levels of influence, intraspinal pathways, etc. Thus, if topical electrical stimulations are applied somewhere in the complex cerebellar
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machinery, stereotype response patterns are likely to be obtained, e.g. in the form of overall inhibitions, while the normal cerebellar coordination might well involve both inhibitory and facilitatory modulations depending on the prevailing input of information. It is known that the cerebellum receives afferent projections also from visceral organs (Widen 1955). From the present data alone it is therefore not possible to decide on what level the cerebellum expresses its autonomic influence. It is, however most unlikely that there are specific cerebellar projections to the effector organs studied; rather the results strongly indicate that the cerebellum modifies the spinal autonomic reflex arcs involved at the bulbar or/and spinal levels. As for the micturition reflex, the cerebellar interaction might take place in the bulbar reticular formation from which descending pathways influence the sacrospinal micturition center. A suppression of the parasympathetic micturition reflex following fastigial stimulation might, however, a priori also be due to sympathetic activation to the bladder, perhaps then occurring as a parallel to the intensified sympathetic drive on the circulatory system that constitutes the fastigial pressor response. The bladder is uia the hypogastric nerve supplied with sympathetic fibres that can induce bladder relaxation (Elliott 1907). In the present study, however, neither pharmacological adrenergic fibre blockade, nor sympathetic fibre section affected the fastigially induced depression of bladder motility. Thus, the bladder inhibitions obtained in the present experiments could not be a consequence of any sympathetic activation. Instead, the cerebellar influence studied here was in all likelihood due to a suppression of the parasympathetically mediated micturition reflex per se, exerted either at the bulbar or spinal levels, as suggested also by Bradley and Teague (1969). Indeed, the fastigial nucleus projects to the bulb and, as can be seen from the drawing in Fig. 6, responses were also obtained from points along the fastigio-bulbar pathways. Although the bladder responses were not exclusively elicited from the fastigial pressor area (Fig. 6), which is restricted to the rostra1 ventromedial fastigial pole, this area proved to be effective in producing both excitatory and inhibitory bladder responses, as well as a generalized suppression of the defecation reflex. These fastigial effects were not at all dependent on the integrity of sympathetic pathways and, consequently, this particular cerebellar area is by no means only engaged in sympathetic control but rather seems to be involved in all kinds of autonomic mechanisms, sympathetic as well as parasympathetic, and also affecting combined autonomic-somatic responses like the defecation reflex. This research has been sponsored by grants from the Swedish Medical Research Council (no. B74-14X16-10C), from Svenska Sallskapet for Medicinsk Forskning and from the Faculty of Medicine, University of Goteborg.
References ACHARI,N. K. and C. B. B. DOWNMAN, Autonomic responses evoked by stimulation of fastigial nuclei in the anaesthetized cat. J. Physiol. (Lond.) 1969. 204. 130 P. BELLER,N. N. and M. I. TALAN, Significance of the cerebellar nuclei for vegetative responses to stimulation of the efferent visceral areas of the cat cerebellar cortex. Sechenou Physiologicul Journal of rhe USSR. 1971. LVII. 29-37. BRADLEY, W. E. and C . T. TEAGUE, Cerebellar influence on the micturition reflex. Exp. Neurol. 1969. 23. 399-411.
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BRUHN,J. M., J. 0. FOLEY, G. M. EMERSON and J. D. EMERSON, Autonomic response to cerebellar stimulation in the decorticate cat. Amer. J. Physiol. 1961. 201. 700-702. CHAMBERS, W. W., Electrical stimulation of the interior of the cerebellum in the cat. Amer. J. Anat. 1947. 80. 55-93. ELLIOTT,T. R., The innervation of the bladder and urethra. J. Physiol. (Lond.) 1907. 35. 367-445. EMERSON, J. D., J. M. BRUHN,G. M. EMERSON and J. 0. FOLEY,Autonomic response to chronic electrode stimulation of cerebellum. Amer. J. Physiol. 1961. 201. 697-699. CARRY, R. C., The response to stimulation of the caudal end of the large bowel in the cat. J. Physiol. (Lond.) 1933. 78. 208-224. HESS,W. R. and M. BRUGGER,Der Miktions- und der Defakationsakt als Erfolg zentraler Reizung. Heiu. physiol. pharmarol. Acba. 1943. 1. 51 1-532. HATCHER,R. A. and S. WEISS,Studies on vomiting. J . Pharmacol. exp. Ther. 1923. 22. 139-193. HULTEN,L., Extrinsic nervous control of colonic motility and blood flow. Acta physiol. scand. 1969. Suppl. 335. KOPPANYI, T., Studies on defecation, with special reference to a medullary defecation centre. J. Lab. elin. Med. 1930. 16. 225-238. LISANDER, B. and J. MARTNER, Interaction between the fastigial pressor response and the defence reaction. Acta physiol. scand. 1973. 87. 359-367. LISANDER, B. and J. MARTNER, Influences on gastrointestinal and bladder motility by the fastigial nucleus. Acta physiol. scand. 1974. 90. 792-794. LISANDER, B. and J. MARTNER, Effects on gastric motility from the cerebellar fastigial nucleus. Artaphysiol. scand. 1975. In press. On the relation between the cerebellar and other centers (namely cereLOWENTHAL, M. and V. HORSLEY, bral and spinal) with special reference to the action of antagonistic muscles. Proc. Roy. Soc. B. 1897. 61. 20-25, MANCHANDA, S. K. and R. BHATTARAI, Autonomic responses to stimulation of paleocerebellum-effects of intercollicular section. Indian J . Physiol. Pharmacol. 1972. 16/4. 329-338. MARTNER, J., Influences o n colonic and small intestinal motility by the cerebellar fastigial nucleus. Acta physiol. scand. 1975. 94. 82-94. MIURA,M. and D. J. REIS, Cerebellum: A pressor response elicited from the fastigial nucleus and its efferent pathway in brainstem. Brain Res. 1969. 13. 595-599. MORLJZZI, G., Ricerche sulla fisiologia del paleocerebellum 1. Riflessi labirintici e cervicali, paleocerebellum e tono posturale. Arch. Fisiol. 1936. 36. 57-112. (Cited in Dow, R. S . and G. Moruzzi, The physiology and pathology of the cerebellum. Univ. of Minnesota Press. Minneapolis. 1958.) MORUZZI,G . , Azione del paleocerebellum sui riflessi vasomotori. Arch. Fisiol. 1938. 38. 36-78. (Cited in Dow, R. S. and G . Moruzzi, The physiology and pathology of the cerebellum. Univ. of Minnesota Press. Minneapolis. 1958.) RASHEED, B. M. A., S. K. MANCHANDA and B. K. ANAND,Effects of the stimulation of paleocerebellum on certain vegetative functions in the cat. Brain Res. 1970. 20. 293-308. ROSTAD,H., Colonic motility in the cat. IV. Peripheral pathways mediating the effects induced by hypothalamic and mesencephalic stimulation. Acfa physiol. scand. 1973. 89. 154-1 68. SCHMIDT, L. and G. FULGRAFF, u b e r einem Rectum-Colon-Reflex. Arzneimittel-Forsch. 1963.13.217-220. SHEEHAN, D., Relationship of the hypothalamus to the large bowel. Amer. J. dig. Dis. 1942. 9. 361-363. WANG,S . C., G. CLARK,F. L. DEY and S. W. RANSON,Further study on the gastrointestinal motility following stimulation of the hypothalamus. Amer. J. Physiol. 1940. 130. 81-88. WHITESIDE, J. A. and R. D. GUYTON,Cerebellar influence on bladder musculature. Anat. Rrc. 1952. 112. 401. WIDBN,L., Cerebellar representation of high threshold afferents in the splanchnic nerve with observations on the cerebellar projection of high threshold somatic afferent fibres. Acfa physiol. scand. 1955. 33. Suppl. 117. WRIGHT,R. D., H. W. FLOREY and M. A. JENNINGS, The secretion of the colon of the cat. Quart J. exp. Physiol. 1938. 28. 207-229. ZANCHETTI, A. and A. ZOCCOLINI, Autonomic hypothalamic outbursts elicited by cerebellar stimulation. J. Neurophysiol. 1954. 17. 475-483.
Influences on the Defecation and Micturition Reflexes by the Cerebellar Fastigial Nucleus BY
JAN MARTNER Received 16 December 1974
Abstract MARTNER, J. Influences of the defecation and micturition reflexes by the cerebellar fastigial nucleus. Acta physiol. scand. 1975. 94. 95-104. The influence of the cerebellar fastigial nucleus on the defecation and micturition reflexes was investigated in chloralosed cats with recordings of colonic blood flow and motility, intravesical and intraabdominal pressures. Whenever effective, topical fastigial stimulation regularly suppressed both somatomotor and autonomic components of the defecation reflex, to the extent that the straining movements as well as the colonic vasodilatator and motor responses associated with defecation could be completely inhibited. Bladder motility could either be suppressed or enhanced, depending both on prevailing bladder tone and on the fastigial site stimulated. The autonomically conveyed inhibitory responses were in both cases independent of the adrenergic sympathetic pathways, since they were unaffected both by sympathetic nerve sectioning and by adrenergic blocking drugs but eliminated by pelvic nerve section. It is suggested that the mentioned fastigial inhibitory influences are exerted on the spinal parasympathetic reflexes controlling the bladder and colon. Parallels between fastigial control of autonomic and somatomotor mechanisms are discussed.
Increasing evidence is accumulating in support of a role for the cerebellum also in autonomic control. Especially interesting in this context is the fastigial nucleus which is very potent in eliciting both cardiovascular (Achari and Downman 1969, Miura and Reis 1969) and gastrointestinal responses (Lisander and Martner 1974) upon electrical stimulation. Both types of responses are induced from the rostra1 ventromedial fastigial pole and involve predominantly a modulation of adrenergic sympathetic discharge, which is enhanced to the circulatory system but as has been recently shown is generally suppressed to the colon and the small intestine (Martner 1975). It was considered of interest to investigate whether also parasympathetically conveyed autonomic responses can be directly influenced from the fastigial nucleus, where especially the defecation and micturition reflexes are of relevance. To fully reveal the fastigial influence on the parasympathetically induced colonic motor responses during defecation, it was necessary to eliminate direct fastigial adrenergic modulation of the colon (Martner 1975). A possible fastigial influence on the defecation reflex is of particular interest also from another point of view, insofar as it involves easily elicited somatomotor and autonomic components. The former requires for its full expression supraspinal levels while the latter 95
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is basically conveyed at spinal sacral levels (Garry 1933) though being considerably influenced also by bulbar and suprabulbar autonomic centres (Hatcher and Weiss 1923, Koppanyi 1930, Hess and Brugger 1943). While the cerebellar control of somatomotor mechanisms is by now fairly well understood, comparatively little is known about the principles of cerebellar autonomic control. Therefore, investigations of cerebellar effects on reflexes that involve both somatomotor and autonomic components might help to elucidate how the cerebellum influences autonomic mechanisms. For such reasons, the first part of the present study deals with the fastigial influences of the somatomotor and autonomic components of the defecation reflex. Concerning the urinary bladder, several authors have reported cerebellar excitatory as well as inhibitory influences, especially from the vermal cortex (Whiteside and Guyton 1952, Emerson et al. 1961, Bruhn et al. 1961, Rasheed, Manchanda and Anand 1970). Also from the fastigial nucleus both micturition (Chambers 1947) and suppression of the micturition reflex (Bradley and Teague 1969) can be elicited and bladder tone can be either increased or decreased (Bellar and Talan 1971, Manchanda and Bhattarai 1972, Lisander and Martner 1974). To further characterize the fastigial structures influencing autonomic mechanisms it was considered of interest to investigate whether they influence also bladder motility in a more regular and specific way. A brief preliminary report covering part of the present results has earlier been presented (Lisander and Martner 1974).
Methods Experiments were performed on 30 cats, anesthetized by chloralose, 50-60 mg/kg b.wt. Free airways were secured by a tracheal cannula. Srimulurions. For cerebellar stimulation the Horsley-Clarke technique was utilized, exploring the fastigial nucleus by electrodes inserted perpendicularly to the horizontal plane. Stimulation was performed via thin monopolar stainless steel electrodes, insulated except for the tip (about 50-100 p m in diameter), using square wave pulses of 1 ms from a constant current stimulator. The intensities used were varied between 0.03 and 0.3 mA (corresponding to a voltage range from 1 to 3.5 V) at a frequency range of 10 to 50 Hz. After each experiment a small lesion was induced around the electrode tip by an anodal current of 1 mA for 10 s. The head of the animal was then perfused by saline followed by a 10% solution of formaldehyde, relevant cerebellar parts were frozen sectioned and the stimulation points identified. Recordings. Arterial pressure was recorded through a femoral catheter connected to a Statham P 23 A C transducer, writing on a Grass polygraph. Heart rate was measured by connecting the pressure recording amplifier to a Grass Tachograph unit. When bladder pressure was recorded, the abdominal wall overlying the urethra was opened by a small incision and a catheter inserted into the bladder via the urethra. Variations in intravesical pressure, reflecting bladder motility, were then recorded by connecting the catheter to a transducer. A saline reservoir, adjustable to various levels, was connected to the catheter via a side branch, thus allowing for bladder filling at different pressures. Sometimes the abdominal incision was extended so that the hypogastric and pelvic nerves could be isolated, placed on ligatures and cut in the course of the experiment. The defecation reflex was elicited either by afferent stimulation of one cut pelvic nerve, the other being left intact, o r by applying a mechanical frictional stimulation to the rectal mucosa (cf. Hulten 1969). For recording colonic motility and blood flow the abdominal wall was opened by a midline incision and the small intestine was extirpated together with the spleen and greater omentum. About 5 cm of the most proximal colonic loop was isolated, gently rinsed from contents and filled with Tyrode solution. The loop was distally isolated by loose ligatures to avoid damage of the intramural nervous connections. Colonic motility was recorded as intraluminal volume changes, transmitted via a wide tube to a container with a diameter of 5 cm mounted on a Grass force displacement transducer FTO 3, thus continuously recording the weight of the container. The level of the container was adjusted to obtain an intraluminal
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m,
I
200 ARTERIAL BLOOD - 0 O PRESSURE, mmHg
-
'
n-
4
0 TIME, I min MECHANICAL STIM. FASTIGIAL STIM
Fig. 1. Cat 3.0 kg. Adrenergic fibres blocked by guanethidine, 4 mg/kg. Mechanical rectal stimulation elicits powerful colonic contractions superimposed o n spontaneous motility. Note that a concomitant fastigial stimulation (50 Hz, 1 ms, 0.04 mA) completely abolishes the colonic motor responses.
pressure of 5-10 cm H,O. Colonic blood flow was determined in heparinized animals by recording the venous outflow from the superior mesenteric vein after extirpation of the small intestine. After passing a closed optical drop recorder, operating an ordinate writer, the blood was returned to the animal via the femoral vein. Drugs. Since respiratory movements sometimes interfered with the colonic events, gallamine iodide (FlaxediP) 4 mg/kg b.wt. i.v. was in these cases given to avoid such disturbances, whereupon artificial respiration was given. N o muscle paralysing drugs were, however, given, when the straining movements in connection with defecation were to be recorded, these were registered as pressure increases in an intraabdominal balloon. In most experiments the secretion from the adrenals was eliminated by encircling ligatures around both glands and adrenocortical substitution was then given by i.v. injection of hydrocortisone (Solu-Gluc@, Erco) 10 mgjkg b.wt. In some experiments the lumbar colonic nerves were dissected free from the inferior mesenteric artery and cut distally to the ganglion but in most cases the adrenergic supply to the colon was instead blocked by guanethidine (Ismelin@,CIBA) 4 mg/kg b.wt. i.v., sometimes in combination with dibenzyline (Smith, Kline and French) 4 mg/kg b.wt. i.v. As an ablocking agent phentolamine (Regitin@,CIBA, 1 mg/kg b.wt. i.v.) was also used. /?'-blockade was induced by propranolol (Inderala, ICI) 0.5-1 mg/kg b.wt. i.v. Atropine (atropine sulphate) was used in a dose of 0.5-1 mg/kg b.wt. i.v.
Results 1. Fastigial influence on defecation Defecationinvolves activation of both somatomotor and autonomic reflexarcs, wherestraining movements increase the intraabdominal pressure and, together with colonic contractions, help to expel the faeces. Colonic vasodilatation also forms part of the pattern (HultCn 1969). All these reflexly induced changes were found to be influenced by fastigial stimulation. As illustrated in Fig. 1, the reflex colonic contractions elicited by mechanical rectal stimulation could be completely suppressed in the adrenergically blocked animals. This was the case in 7 cats and only in 2 expts. fastigial stimulation failed to attenuate the colonic response. Likewise, reflex colonic contractions induced by afferent pelvic nerve stimulation were inhibited as well ( 2 cats). Atropine reduced but did not eliminate the reflex colonic contractions and the small remaining reflex motor responses to rectal stimulation were also suppressed by fastigial stimulation. Fig. 2 shows that the straining movements, reflexly induced by afferent pelvic nerve stimulation, could be completely suppressed by fastigial stimulations. Mechanical rectal 7 - 755875
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200 ARTERIAL BLOOD PRESSURE, m m Hg loo
TIME, I rnin FASTIGIAL STIM. AFFERENT PELVIC NERVE STIM.
Fig. 2. Cat 2.0 kg. The lumbar colonic nerves and left pelvic nerve cut. Afferent pelvic nerve stimulation induces straining movements recorded as intermittent increases in intraabdominal pressure. Note that fastigial stimulation (50 Hz, 1 ms, 0.2 mA) completely blocks the somatomotor straining movements.
stimulation in one cat elicited reproducible straining movements and they, too, were inhibited by fastigial stimulation. In 3 expts. colonic blood flow was recorded in order to explore the fastigial influence on the colonic vasodilatation accompanying the defecation reflex. Fig. 3 shows such a sequence, intentionally chosen late in the experiment when the colon, perhaps due to deterioration, no longer exhibited any appreciable motor responses that could mechanically interfere with the reflex vasodilatation. Also this latter response could be completely suppressed by fastigial stimulation which, in itself, did not influence colonic blood flow in the adrenergically blocked animal. This was the case in all 3 expts. where a reflex vasodilator response could be repeatedly elicited, whether by means of afferent pelvic nerve stimulation or by mechanical rectal stimulation. In no case did any facilitation of the components comprising the defecation reflex occur. The responsive fastigial area corresponded well with that from which sympathetically mediated blood pressure rises are elicited and was located in the ventromedial part of the rostra1 fastigial pole. For reasons discussed below most animals were adrenergically blocked after that the fastigial pressor area had been identified. Fig. 6, right side of each drawing, summarizes the localization of the points effective in suppressing the defecation reflex, the different components of which seem to be intermingled and coinciding with the fastigial pressor area.
2. Fustigiul influence on bladder motility Filling the bladder with saline regularly induced spontaneous contractions which could markedly raise intravesical pressure. If the bladder outlet was occluded, this increased bladder pressure was sustained enough as to allow an exploration whether, and in which direction, it was affected by cerebellar stimulation. Total bladder inhibition as a result of fastigial stimulation was observed in all 17 cats tested in this way. As shown in Fig. 4 the suppression of bladder motility was prompt and maintained throughout the fastigial stimulation. However, inhibitory bladder responses could be elicited also from fastigial structures outside the fastigial pressor area, which is evident from panel A where the first stimulation
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I PROXIMAL COLON MOTILITY
5ml]
COLON C BLOOD FLOW.30 ml/min s 1000 50
TIME,
I min
FASTIGIAL STIM. MECHANICAL STIM.
Fig. 3. Cat 3.3 kg. The adrenergic fibres blocked by a combination of guanethidine 4 mg/kg b.wt., and dibenzyline, 4 mgjkg b.wt. Mechanical rectal stimulation induces reflex colonic vasodilatation which is independent of motility changes. Note that fastigial stimulation (50 Hz, 1 ms, 0.1 mA) totally abolishes this reflex vasodilatation while fastigial stimulation p e r se has no effect on colonic blood flow.
was performed with the electrode placed 1.5 mm dorsally to the pressor area. The electrode was then lowered 1.5 mm (second stimulation, panel A) into the pressor area and still bladder inhibition was obtained. If the bladder contraction was allowed to spontaneously subside and fastigial stimulation was again repeated a small "rebound" bladder contraction was occasionally observed upon cessation of the stimulation. The fastigial suppression of bladder motility was not due to activation of sympathetic adrenergic fibres since neither guanethidine (4 mg/kg b.wt.) nor a combination of a- and /3-adrenergic blocking agents (phentolamine 1 mg/kg b.wt. and propranolol 1 mg/kg b.wt.) could abolish the fastigial responses (Fig. 4, panel B). Moreover, sectioning of the sympathetic hypogastric nerves to the bladder did not influence the fastigial inhibitory responses. Cutting the pelvic nerves eliminated reflexly induced bladder contraction and no inhibitory A
B
200 PRESSURE, BLOOD ARTERIAL mm Hg -001
I00 BLADDER PRESSURE,
cm HzO
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FASTIGIAL STIM.
Fig. 4. Cat 3.0 kg. Effect on bladder motility by fastigial stimulation (50 Hz, 1 rns, 0.1 mA). Inhibition of reflexly induced bladder contraction can he accomplished from cerebellar sites both above and within the fastigial pressor area (first and second stimulation, panel A). Complete adrenergic blockade with guanethidine 4 mg/kg b.wt., phentolamine 1 mg/kg b.wt. and propranolol 1 mg/kg b.wt. does not abolish the inhibitory effect of fastigial stimulation (panel B).
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BLADDER PRESSURE, crn H,O
ARTERIAL BLOOD PRESSURE, mrn Hg
TIME,
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FASTIGIAL STIM.
Fig. 5. Cat 2.8 kg. Fastigial stimulation (50 Hz, 1 ms, 0.1 mA) induces inhibition of bladder motility when performed against a background of high, sustained intravesical pressure (panel A). The same fastigial site elicits bladder contraction if stimulation is performed during a background of low bladder tone. The small oscillations in bladder pressure seen during bladder inhibition are due to respiratory movernents.
fastigial influence could now be traced. Atropine (1 mg/kg b.wt.) substantially reduced the reflex bladder contractions but fastigial stimulation suppressed also the small remaining contraction waves. Bladder contractions could also result upon fastigial stimulation although they were not so easily demonstrated as were the bladder inhibitions. However, once appearing they could be quite prominent (Fig. 5, panel B). This figure further illustrates that the very same fastigial point, from which excitatory responses could be elicited (panel B), could also depress bladder motility, once a pronounced and sustained reflex bladder tone was at hand (panel A). Neither the excitatory nor the inhibitory bladder response were strictly confined to the fastigial pressor area although the former type of response was usually associated with the pressor response. The left side of Fig. 6 summarizes the points from which bladder responses were elicited. The fastigial nucleus can evidently not be divided into one excitatory and one inhibitory area in this very respect, even though the bladder inhibitory responses (open triangles) tend to cover a larger area. Contrary to most other fastigial autonomic effects, including bladder excitation, the inhibitory bladder response seems to follow an “all or nothing law”. Thus, while low stimulation frequencies did not noticeably influence bladder tone, a gradual frequency increase suddenly induced total suppression of bladder contraction, usually when 10-20 Hz were reached. This frequency range corresponds well with that where fastigial influences on e.g. blood pressure and gastrointestinal motility become obvious (Lisander and Martner 1975). However, the latter type of responses, essentially dependent of discharge changes in the sympathetic adrenergic fibres, are characterized by a gradually rising frequency-response curve which reaches a plateau at 40-50 Hz, while the parasympathetically mediated bladder inhibitory responses, once appearing, were then always maximal, i.e. producing 100 per cent suppression of the bladder motility.
FASTIGIAL INFLUENCE ON DEFECATION AND MICTURITION
Fig. 6 . Cerebellar frontal sections, 8 and 8.5 mm posterior to the interaural line. The bladder responses are shown to the left and the defecation responses to the right. Open circles: N o response. Open triangles: Inhibitory bladder responses. Filled triangles: Excitatory bladder responses. Filled dots: Suppression of colonic motor responses. Filled squares: Suppression of colonic vasodilatation. Open squares: Suppression of straining movements. Nf: Nucleus fastigius. Vq: Ventriculus quartus.
P 0.0
101
P 0.5
Discussion Colonic motility elicited from the rectum includes profound reflex contractions particularly of the proximal but also of the distal colon (Schmidt and Fulgraff 1963), where both afferent and efferent pathways run in the pelvic nerves (HultCn 1969). The defecation reflex can be elicited either by mechanical rectal stimulation or by pelvic afferent stimulation. In both cases fastigial stimulation could completely abolish the colonic motor response, showing that the fastigial influence cannot be a matter of e.g. any neurogenically conveyed suppression of receptor sensitivity in the rectal mucosa. Hypothalamic stimulation can inhibit spontaneous colonic motility (Wang et al. 1940, Sheehan 1942, Rostad 1973) and the latter investigator found that this inhibitory effect was abolished by adrenergic blockade. In contrast, the fastigially induced suppressions of reflex colonic motility reported here were due to a direct inhibition of the parasympathetically mediated defection reflex and were not a matter of any activation of colonic sympathetic fibres, obvious from the fact that all animals used were subject either to pharmacological adrenergic fibre blockade or to section of the lumbar colonic nerves. This procedure was also necessary for the full expression of the parasympathetically mediated reflex colonic motor and vasodilator responses, which are known to be suppressed by a prevailing sympathetic discharge, presumably at the intramural ganglionic level (HultCn 1969). Moreover, the fastigial influence on spontaneous colonic motility in cats is excitatory in nature and mediated by a suppression of prevailing sympathetic discharge (Lisander and Martner 1974). Elimination of the sympathetic inhibitory influence on parasympathetically mediated colonic responses, which would certainly interfere with the present type of study, was another reason for using various kinds of adrenergic blockade. Ligation of the adrenals excluded the possibility that the fastigial inhibition of the reflex colonic motility was mediated by a release of catecholamines from the adrenal medulla (Lisander and Martner 1973). Besides influencing colonic motor activity, fastigial stimulation could also completely suppress the reflex vasodilatation accompanying defecation. Efferent pelvic nerve stimulation elicits mucosal vasodilatation and secretion (Wright, Florey and Jenning 1938) and HultCn (1969) showed that the vasodilatation forms part of the defecation reflex and is neither eliminated by adrenergic nor by cholinergic blocking agents. Whichever the trans-
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mittor mechanism involved at these parasympathetic nerve endings, the fastigial nucleus could completely suppress this vascular response. Interestingly, the somatomotor component of the defecation reflex was affected by the same fastigial area and in the same inhibitory way as the autonomic components. Thus, total suppression of the straining movements was always induced by fastigial stimulation. Cerebellar modulations of somatomotor mechanisms are wellknown ever since Lowenthal and Horsley (1 897) reported inhibition of decerebrate rigidity by cerebellar stimulation. Since the fastigial nucleus always modified the somatomotor and autonomic components of the defecation reflex in the same direction it seems likely that cerebellar control may be exerted according to similar principles both concerning somatomotor and autonomic mechanisms. In fact, other parallels between the cerebellar influence on somatomotor and autonomic mechanisms d o exist and can be illustrated e.g. by comparing wellknown cerebellar somatomotor effects with the results obtained on bladder autonomic functions. It was found in the present experiments that the fastigial nucleus could both inhibit and augment bladder motility, in consonance with the findings of Beller and Talan (1971) and Manchanda and Bhattarai (1972). Determinant of the direction of the response was both the prevailing bladder tone and the cerebellar site stimulated. Thus, moving the electrode only 0.5 mm sometimes changed an inhibitory response into an excitatory one. Such a reversal could be obtained even from the same fastigial site; inhibitions occurring during periods of reflexly induced bladder contractions, but changing into excitatory responses when the contractions had spontaneously subsided. Similar effects have been induced from the cerebellar cortex (Whiteside and Guyton 1952). The same kind of variable cerebellar influence, depending on background activity, has been illustrated also concerning the cardiovascular system (Moruzzi 1938) and is also demonstrated concerning somatomotor reflexes (Moruzzi 1936). Thus, cerebellar stimulation produced inhibition of extensor hypertonia in decerebrate cats, while increased extensor tone was occasionally recorded if stimulation was undertaken during hypotonia, sometimes as a rebound effect at the end of the stimulation. Such rebound phenomena have been observed both for the autonomic and somatomotor components of the defence reaction during sham rage (Zanchetti and Zoccolini 1954) and were also observed concerning the purely autonomic responses of the bladder in the present study. The finding that cerebellar stimulation produced a constant and generalized inhibition of e . g . the defecation reflex in the present experiments does, however, not necessarily imply that the cerebellum normally always exerts a suppressive influence in these respects. Electrical stimulation of specific brain areas does not necessarily simulate in vivo patterns in a precise way. For example, such stimulations excite, certainly also antidromically and without discrimination, both afferent and efferent pathways and may affect both fibres and neuron somata. Hence, if effects can be demonstrated in the form of fastigial suppression of defecation and micturition, as in this case, it no doubt indicates that the cerebellum is involved in the control of these reflexes but reveals little about the way by which it is normally brought about, whether concerning levels of influence, intraspinal pathways, etc. Thus, if topical electrical stimulations are applied somewhere in the complex cerebellar
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machinery, stereotype response patterns are likely to be obtained, e.g. in the form of overall inhibitions, while the normal cerebellar coordination might well involve both inhibitory and facilitatory modulations depending on the prevailing input of information. It is known that the cerebellum receives afferent projections also from visceral organs (Widen 1955). From the present data alone it is therefore not possible to decide on what level the cerebellum expresses its autonomic influence. It is, however most unlikely that there are specific cerebellar projections to the effector organs studied; rather the results strongly indicate that the cerebellum modifies the spinal autonomic reflex arcs involved at the bulbar or/and spinal levels. As for the micturition reflex, the cerebellar interaction might take place in the bulbar reticular formation from which descending pathways influence the sacrospinal micturition center. A suppression of the parasympathetic micturition reflex following fastigial stimulation might, however, a priori also be due to sympathetic activation to the bladder, perhaps then occurring as a parallel to the intensified sympathetic drive on the circulatory system that constitutes the fastigial pressor response. The bladder is uia the hypogastric nerve supplied with sympathetic fibres that can induce bladder relaxation (Elliott 1907). In the present study, however, neither pharmacological adrenergic fibre blockade, nor sympathetic fibre section affected the fastigially induced depression of bladder motility. Thus, the bladder inhibitions obtained in the present experiments could not be a consequence of any sympathetic activation. Instead, the cerebellar influence studied here was in all likelihood due to a suppression of the parasympathetically mediated micturition reflex per se, exerted either at the bulbar or spinal levels, as suggested also by Bradley and Teague (1969). Indeed, the fastigial nucleus projects to the bulb and, as can be seen from the drawing in Fig. 6, responses were also obtained from points along the fastigio-bulbar pathways. Although the bladder responses were not exclusively elicited from the fastigial pressor area (Fig. 6), which is restricted to the rostra1 ventromedial fastigial pole, this area proved to be effective in producing both excitatory and inhibitory bladder responses, as well as a generalized suppression of the defecation reflex. These fastigial effects were not at all dependent on the integrity of sympathetic pathways and, consequently, this particular cerebellar area is by no means only engaged in sympathetic control but rather seems to be involved in all kinds of autonomic mechanisms, sympathetic as well as parasympathetic, and also affecting combined autonomic-somatic responses like the defecation reflex. This research has been sponsored by grants from the Swedish Medical Research Council (no. B74-14X16-10C), from Svenska Sallskapet for Medicinsk Forskning and from the Faculty of Medicine, University of Goteborg.
References ACHARI,N. K. and C. B. B. DOWNMAN, Autonomic responses evoked by stimulation of fastigial nuclei in the anaesthetized cat. J. Physiol. (Lond.) 1969. 204. 130 P. BELLER,N. N. and M. I. TALAN, Significance of the cerebellar nuclei for vegetative responses to stimulation of the efferent visceral areas of the cat cerebellar cortex. Sechenou Physiologicul Journal of rhe USSR. 1971. LVII. 29-37. BRADLEY, W. E. and C . T. TEAGUE, Cerebellar influence on the micturition reflex. Exp. Neurol. 1969. 23. 399-411.
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BRUHN,J. M., J. 0. FOLEY, G. M. EMERSON and J. D. EMERSON, Autonomic response to cerebellar stimulation in the decorticate cat. Amer. J. Physiol. 1961. 201. 700-702. CHAMBERS, W. W., Electrical stimulation of the interior of the cerebellum in the cat. Amer. J. Anat. 1947. 80. 55-93. ELLIOTT,T. R., The innervation of the bladder and urethra. J. Physiol. (Lond.) 1907. 35. 367-445. EMERSON, J. D., J. M. BRUHN,G. M. EMERSON and J. 0. FOLEY,Autonomic response to chronic electrode stimulation of cerebellum. Amer. J. Physiol. 1961. 201. 697-699. CARRY, R. C., The response to stimulation of the caudal end of the large bowel in the cat. J. Physiol. (Lond.) 1933. 78. 208-224. HESS,W. R. and M. BRUGGER,Der Miktions- und der Defakationsakt als Erfolg zentraler Reizung. Heiu. physiol. pharmarol. Acba. 1943. 1. 51 1-532. HATCHER,R. A. and S. WEISS,Studies on vomiting. J . Pharmacol. exp. Ther. 1923. 22. 139-193. HULTEN,L., Extrinsic nervous control of colonic motility and blood flow. Acta physiol. scand. 1969. Suppl. 335. KOPPANYI, T., Studies on defecation, with special reference to a medullary defecation centre. J. Lab. elin. Med. 1930. 16. 225-238. LISANDER, B. and J. MARTNER, Interaction between the fastigial pressor response and the defence reaction. Acta physiol. scand. 1973. 87. 359-367. LISANDER, B. and J. MARTNER, Influences on gastrointestinal and bladder motility by the fastigial nucleus. Acta physiol. scand. 1974. 90. 792-794. LISANDER, B. and J. MARTNER, Effects on gastric motility from the cerebellar fastigial nucleus. Artaphysiol. scand. 1975. In press. On the relation between the cerebellar and other centers (namely cereLOWENTHAL, M. and V. HORSLEY, bral and spinal) with special reference to the action of antagonistic muscles. Proc. Roy. Soc. B. 1897. 61. 20-25, MANCHANDA, S. K. and R. BHATTARAI, Autonomic responses to stimulation of paleocerebellum-effects of intercollicular section. Indian J . Physiol. Pharmacol. 1972. 16/4. 329-338. MARTNER, J., Influences o n colonic and small intestinal motility by the cerebellar fastigial nucleus. Acta physiol. scand. 1975. 94. 82-94. MIURA,M. and D. J. REIS, Cerebellum: A pressor response elicited from the fastigial nucleus and its efferent pathway in brainstem. Brain Res. 1969. 13. 595-599. MORLJZZI, G., Ricerche sulla fisiologia del paleocerebellum 1. Riflessi labirintici e cervicali, paleocerebellum e tono posturale. Arch. Fisiol. 1936. 36. 57-112. (Cited in Dow, R. S . and G. Moruzzi, The physiology and pathology of the cerebellum. Univ. of Minnesota Press. Minneapolis. 1958.) MORUZZI,G . , Azione del paleocerebellum sui riflessi vasomotori. Arch. Fisiol. 1938. 38. 36-78. (Cited in Dow, R. S. and G . Moruzzi, The physiology and pathology of the cerebellum. Univ. of Minnesota Press. Minneapolis. 1958.) RASHEED, B. M. A., S. K. MANCHANDA and B. K. ANAND,Effects of the stimulation of paleocerebellum on certain vegetative functions in the cat. Brain Res. 1970. 20. 293-308. ROSTAD,H., Colonic motility in the cat. IV. Peripheral pathways mediating the effects induced by hypothalamic and mesencephalic stimulation. Acfa physiol. scand. 1973. 89. 154-1 68. SCHMIDT, L. and G. FULGRAFF, u b e r einem Rectum-Colon-Reflex. Arzneimittel-Forsch. 1963.13.217-220. SHEEHAN, D., Relationship of the hypothalamus to the large bowel. Amer. J. dig. Dis. 1942. 9. 361-363. WANG,S . C., G. CLARK,F. L. DEY and S. W. RANSON,Further study on the gastrointestinal motility following stimulation of the hypothalamus. Amer. J. Physiol. 1940. 130. 81-88. WHITESIDE, J. A. and R. D. GUYTON,Cerebellar influence on bladder musculature. Anat. Rrc. 1952. 112. 401. WIDBN,L., Cerebellar representation of high threshold afferents in the splanchnic nerve with observations on the cerebellar projection of high threshold somatic afferent fibres. Acfa physiol. scand. 1955. 33. Suppl. 117. WRIGHT,R. D., H. W. FLOREY and M. A. JENNINGS, The secretion of the colon of the cat. Quart J. exp. Physiol. 1938. 28. 207-229. ZANCHETTI, A. and A. ZOCCOLINI, Autonomic hypothalamic outbursts elicited by cerebellar stimulation. J. Neurophysiol. 1954. 17. 475-483.
