Biomedical subjects
Publications and source records attributed to B Tantisira.
Starting from amino(di)azines and 2-chloro-6-methyliso(thio)cyanate a series of aryl-substituted urea and thiourea derivatives was prepared and screened as potential antiepileptics. Among the new derivatives tested, only 2b and 3c exhibited adequate anticonvulsant effects, whereas 3d and 4d were found to be convulsants per se.
Cats were trained to reach to an illuminated tube placed horizontally at shoulder level and retrieve food with the forepaw. The trajectory of an infrared light emitting diode, taped to the wrist dorsum, was recorded with a SELSPOT-like recording system. Movement paths and velocity profiles were compared before and after lesions: (1) in dorsal C5, transecting cortico- and rubrospinal pathways to the forelimb segments so that the cats could only use the C3-C4 propriospinal neurones (PNs) to command reaching, (2) in the ventral part of the lateral funicle in C5, transecting the axons of C3-C4 PNs so that the cats had to use circuitry in the forelimb segments to command reaching. Comparison of trajectories and velocity profiles before and after lesion 1 did not reveal any major qualitative change. After lesion 2, the last third of the movement was fragmented with separate lifting and protraction. Switching of target-reaching occurred when illumination was shifted to another tube during the ongoing movement. The switching latency measured from the time of illumination shift to the earliest change in movement trajectory had a minimal value of 50-60 ms. Short latencies were present after lesion 1 as well as lesion 2 which suggest that fast switching mediated by the C3-C4 PNs and the interneuronal system in the forelimb segments is controlled in parallel by the brain. In order to test a hypothesis that fast switching depends on the tectospinal and tecto-reticulospinal pathways (the tecto-reticulo-spinal system) a ventral lesion was made in C2 aiming at interrupting these pathways. Large ventral C2 lesions tended to block conduction in the more dorsally located rubrospinal (less in corticospinal) axons probably due to compression during surgery. When conduction in the rubrospinal tract was completely interrupted by a ventral C2 lesion which also completely transected the axons of the tecto-reticulo-spinal system, then there was a prolongation of the switching latency with 10-20 ms. After a similar large ventral lesion with remaining conduction in the rubrospinal tract the switching latencies were unchanged. It is postulated that fast visually governed switching does not depend on the tecto-reticulo-spinal system alone but on more dorsally located pathways, presumably the rubrospinal tract, either acting alone or together with the tecto-reticulo-spinal system. It is further postulated that the delayed switching after interruption of conduction both in the rubrospinal tract and the tecto-reticulo-spinal system depends on the corticospinal tract. Visual control of rubrospinal and of corticospinal neurones is considered. It is postulated that target-reaching normally depends on signals in the cortico- and rubrospinal tracts and mechanisms for co-ordination of activity in them as required during switching is discussed in view of the findings now reported.
STUDY OBJECTIVES: To test the hypothesis that for major gynecologic surgery the combination of propofol for induction, ondansetron, and dexamethasone would be a more effective antiemetic combination than propofol for induction, ondansetron, and saline; and to determine if a propofol induction of anesthesia improved our previously reported results when thiamylal was the induction drug. DESIGN: Double-blind, randomized study. SETTING: Magee-Womens Hospital, Pittsburgh, Pennsylvania. PATIENTS: 80 healthy ASA physical status I, II, and III female inpatients scheduled for major gynecologic surgery. INTERVENTIONS: After induction of anesthesia with propofol, Group 1 received intravenous (IV) ondansetron 4 mg and saline, and Group 2 received IV ondansetron 4 mg followed by IV dexamethasone 20 mg. MEASUREMENTS AND MAIN RESULTS: For Group 1 and Group 2, respectively, no emesis and no rescue occurred in 15 (37.5%) and 21 (52.5%) patients (p = 0.13); emesis occurred in 7 (17.5%) Group 1 patients and 5 (12.5%) Group 2 patients, rescue antiemetic 23 (57.5%) Group 1 patients and 19 (47.5%) Group 2 patients. Nausea was reported by 31 (77.5%) Group 1 patients and 30 (75%) Group 2 patients. CONCLUSIONS: The hypothesis that the addition of dexamethasone to the propofolondansetron combination would significantly reduce postoperative nausea and vomiting (PONV) was not confirmed. A propofol induction of anesthesia resulted in a comparable incidence of PONV when compared with our previously reported results using thiamylal for induction of anesthesia for women having major gynecologic operations.
Anticonvulsant activity, lethality and neurotoxicity of a valproic acid (VPA) analog, N-(2-propylpentanoyl) urea (VPU) in comparison to its parent compound were investigated in mice. Intraperitoneally administered VPU demonstrated a higher protection than VPA in both the maximal electroshock seizure (MES) and the pentylenetetrazole (PTZ) tests exhibiting a median effective dose (ED50) of 66 and 57 mg/kg, respectively. VPU weakly blocked the effect of bicuculline and was ineffective in strychnine test. Furthermore, VPU was also active orally demonstrating an ED50 approximately 6 times higher than its ED50 by the intraperitoneal route. Based on the relatively high median lethal dose (LD50), 1553 mg/kg, VPU possesses a greater margin of safety (LD50/ED50) than did VPA. Unwanted (side) effects in terms of impairment of motor activity and neurotoxicity were assessed by the rotorod test, locomotor activity test as well as potentiation of barbiturate sleeping time. The median neurotoxic dose (TD50) as measured by rotorod test were 625 mg/kg for intraperitoneally given VPU. This finding results in higher protective index (PI = TD50/ED50) of VPU (PI = 9.5) than that of VPA (PI = 1.1) implying that, in therapeutic dose, VPU may produce less neurological side effects than did VPA. Superiority of VPU in terms of higher potency in parallel with minimal neurological deficit as assessed by rotorod test was evident throughout the observation period of 12 hours. Similar results on locomotor activity as well as potentiation of barbiturate sleeping time were obtained with VPU and VPA. Thus, VPU is preferably expected to exert minor degree of CNS depression. Taken altogether, our findings demonstrate greater anticovulsant activity for VPU than for VPA. In addition, this compound is also orally active and seems to offer a greater safety margin in parallel with lower unwanted effects in relation to its parent compound. As indicated by the animal data obtained, VPU is an attractive anticonvulsant candidate for further investigation.
The pattern of motoneuronal projection and termination of single C3-C4 propriospinal neurones in the forelimb segments C6-T1 of the cat was investigated by intra-axonal injection of horseradish peroxidase into stem axons. Twelve well-stained axons were used for analysis. Termination was observed in the estimated location of motor nuclei innervating pure shoulder muscles in 10 cases. Among motoneurones innervating shoulder, elbow, wrist, and digit muscles, projection and termination were observed in motor nuclei controlling muscles of two or three joints in the following combinations: shoulder + elbow, shoulder + wrist, shoulder + elbow + wrist, shoulder + elbow + digit, and elbow + wrist + digit. In one case it was difficult to exclude the possibility of projection and termination in motor nuclei controlling muscles at all four joints. These patterns of motoneuronal projection from C3-C4 propriospinal neurones are compatible with their function in mediating the descending command for visually guided target reaching movements with the forelimb. In addition, it was found that the C3-C4 propriospinal neurones project and terminate in the region of ventral and ventromedial motor nuclei, which innervate axial muscles acting on the trunk. This was confirmed by intracellular recording from presumed ventromedial motoneurones in the C6-C7 segments. It is postulated that the C3-C4 propriospinal neurones, in addition to their control of forelimb movements, provide for conjoint control of axial muscles to stabilize the trunk during target reaching.
STUDY OBJECTIVES: To evaluate the antiemetic effectiveness and side effects of adding low-dose droperidol to morphine delivered via a patient-controlled analgesia (PCA) device. DESIGN: Randomized, double-blind, clinical study. SETTING: University-affiliated women's hospital. PATIENTS: 60 healthy women, 18 to 60 years of age, who underwent total abdominal hysterectomy with a standardized anesthetic regime. INTERVENTIONS: After surgery, the control group (n = 20) had access via PCA to two cartridges, each containing morphine 1 mg/ml and saline 1 ml. The two treated groups (n = 20 each) had access via PCA to either droperidol 0.5 mg or droperidol 1 mg added to two cartridges containing morphine 1 mg/ml. MEASUREMENTS AND MAIN RESULTS: Preoperative data, including each patient's history of nausea and vomiting with and without previous anesthesia, motion sickness, smoking, and alcohol intake, and date of her last menstrual period, were obtained. All patients received a standardized anesthetic with droperidol 0.5 mg given at closure of the peritoneum. Among those patients who received droperidol added to morphine for their postoperative analgesic regimen, fewer required rescue antiemetic medication (p < 0.05, test of trend in proportions), and they had a lower incidence of vomiting (p < 0.05, test of trend in proportions), as well as a decrease in the number of times a rescue antiemetic was needed during the 24-hour postoperative period (linear trend, p = 0.013). CONCLUSIONS: An intermittent intake of low-dose droperidol with morphine given via a PCA delivery system in two treatment groups gave evidence for a dose-response relation between the amount of droperidol added and the proportion of patients needing a rescue antiemetic. The same result applied to the proportion of patients having an emetic episode and the number of times a rescue antiemetic had to be administered. There was no evidence that the low dose of droperidol added to morphine delivered via a PCA device increased unwanted side effects.
The purpose of this double-blind, randomized study was to compare the effectiveness of ondansetron plus saline versus ondansetron plus dexamethasone in the prevention of postoperative nausea and vomiting. Of 180 women having general anesthesia for major gynecologic surgery, 89 received intravenous ondansetron, 4 mg, plus saline (Group 1) and 91 received intravenous ondansetron, 4 mg, plus dexamethasone 8 mg (Group 2) during their operation. A complete response, defined as no emesis and no need for rescue antiemetic during the 24-h postoperative period, occurred in 38% of patients in Group 1 and in 52% in Group 2 (P = 0.048). Emesis occurred in 34% of patients in Group 1 and in 15% in Group 2 (P = 0.003). Nausea scores were significantly lower for patients in Group 2 at 2 h (P = 0.023) and at 24 h (P = 0.001). In the ondansetron plus dexamethasone group, 9 out of 10 patients who received propofol for induction of anesthesia had no emesis. The only failure occurred in a patient who had a single emetic episode during the 24th postoperative hour. The combination of ondansetron and dexamethasone was more effective than ondansetron and saline in the prevention of postoperative nausea and vomiting for women having major gynecologic surgery.
Trajectory formation of unrestrained forelimb target-reaching was investigated in six cats. A Selspot-like recording system was used for three-dimensional recording of the position of the wrist every 3 ms with the aid of two cameras detecting infrared light emitted from diodes taped to the wrist. These measurements allowed reconstruction of movement paths in the horizontal and sagittal planes and velocity profiles in the direction of the cartesian x, y and z co-ordinates. Horizontal movement paths were smoothly curved, segmented or almost linear. Sagittal movement paths were sigmoid. The net velocity profile was usually bell-shaped with longer deceleration than acceleration, but for some slow movements the velocity profile had a plateau. When the net velocity profile was bell-shaped, the averaged sagittal movement paths and normalized x (protraction) and z (lifting) velocity profiles were virtually superimposable for fast and slow movements: thus, movement speed was changed by parallel scaling of protraction and lifting. Comparison of movement paths and velocity profiles amongst the different cats revealed considerable differences. The x profile was unimodal in one cat and double peaked in five cats: the second component was pronounced in two cats and small in the other three. The z profile was unimodal and, except for one cat, it had later onset and summit than the first component of the x profile. In contrast to the interindividual differences, there was a high degree of intraindividual constancy over 6-12 months. It is postulated that the interindividual variability depends on chance differences established early during learning of the task and that the imprinted pattern remains, resulting in intra-individual constancy.
Trajectory formation of unrestrained forelimb target-reaching was investigated in relation to the effect of a change in target location. Sagittal displacement of the target (6 cm in each direction) gave a selective change of velocity in the x direction (protraction) with an increase or decrease at larger and shorter distances, respectively. In the case of a double-peaked x velocity profile, the change was mainly with respect to the first major component. The shape of the y (sideways) and of the z (lifting) velocity profiles were both almost unchanged, but the onset of the movement in the z direction changed with the x distance. Vertical displacement (4 cm up or 5 cm down) gave increased velocity in the z direction (lifting) when the target was above the normal mid-position and decreased velocity when the target was lower. The velocity was changed with constant rate of rise, so that the rise time increased when the target was elevated and shortened when the target was lowered (pulse width control policy). The change in the z velocity was not selective. In cats with a double-peaked x velocity profile, the second component decreased when the target was elevated and increased when it was lowered. With excessive lowering of the target (14 cm down), the first x velocity component was very much reduced in amplitude so that protraction depended mainly on the second x velocity component. In the cat with a unimodal x velocity profile, a second component appeared in the x and net velocity profiles when the target was excessively lowered.(ABSTRACT TRUNCATED AT 250 WORDS)
Excitation of dorsal neck motoneurones evoked by electrical stimulation of primary trigeminal afferents in the Gasserian ganglion has been investigated with intracellular recording from alpha-motoneurones in the cat. Single stimulation in the Gasserian ganglion ipsi- and contralateral to the recording side evoked excitatory postsynaptic potentials (EPSPs) in motoneurones innervating the lateral head flexor muscle splenius (SPL) and the head elevator muscles biventer cervicis and complexus (BCC). The gasserian EPSPs were composed of early and late components which gave the EPSPs a hump-like shape. A short train of stimuli, consisting of two to three volleys, evoked temporal facilitation of both the early and late EPSP components. The latencies of the gasserian EPSPs ranged from 1.6 to 3.6 ms in SPL motoneurones and from 1.6 to 5.8 ms among BCC motoneurones. A rather similar latency distribution between 1.6 and 2.4 ms was found for ipsi- and contralateral EPSPs in SPL and BCC motoneurones, which is compatible with a minimal disynaptic linkage between primary trigeminal afferents and neck motoneurones. Systematic transections of the ipsi- and contralateral trigeminal tracts were performed in the brain stem between 3 and 12 mm rostral to the level of obex. The results demonstrate that both the ipsi- and contralateral disynaptic and late gasserian EPSPs can be mediated via trigeminospinal neurones which take their origin in the nucleus trigeminalis spinalis oralis. Transection of the midline showed that the contralateral trigeminospinal neurones cross in the brain stem. Systematic tracking in and around the ipsilateral trigeminal nuclei demonstrated that the axons of ipsilateral trigeminospinal neurones descend just medial to and/or in the medial part of the nucleus. Spinal cord lesions revealed a location of the axons of the ipsilateral trigeminospinal neurones in the lateral and ventral funiculi. Interaction between the ipsi- and contralateral gasserian EPSPs showed complete summation of the disynaptic EPSP component, while the late components were occluded by about 45%. These results show that the disynaptic EPSPs are mediated by separate trigeminospinal neurones from the ipsi- and contralateral side, while about half of the late EPSPs are mediated by common neurones which receive strong bilateral excitation from commissural neurones in the trigeminal nuclei. Spatial facilitation was found in the late gasserian EPSP but not in the disynaptic gasserian EPSP by conditioning stimulation of cortico- and tectofugal fibres. Disynaptic pyramidal and tectal EPSPs, which are mediated by reticulospinal neurones, were facilitated by a single stimulation in the gasserian ganglion at an optimal interval of 2 ms.(ABSTRACT TRUNCATED AT 400 WORDS)
1. The effect of stimulating the contralateral pyramid has been investigated with intracellular recording from 128 long propriospinal neurones (long PNs) in the C3-Th1 segments of the cat. Long PNs were identified by the antidromic activation from the Th13 segment. They were located in laminae VII-VIII of Rexed. Single pyramidal stimulation evoked monosynaptic EPSPs in 15/40 of the long PNs in cats with intact pyramid. In 15 other long PNs, a train of three to four pyramidal stimuli evoked EPSPs with latencies indicating a minimal disynaptic linkage. The remaining 25% of the long PNs lacked mono- or disynaptic pyramidal EPSPs. In a few cases longer latency excitation was observed. 2. The location of the intercalated neurones which mediate the disynaptic pyramidal EPSPs was investigated by making four different lesions of the corticofugal fibres: 1) at the border of the C5 and C6 segments, 2) at the border of the C2 and C3 segments, 3) at the caudal part of the pyramid; three mm rostral to the decussation and 4) at the level of the trapezoid body. Stimulation of the corticofugal fibres was made either rostral to lesion 3 (rPyr) in order to activate neurones in a cortico-bulbospinal pathway or caudal to lesion 3 (cPyr) to activate neurones in a corticospinal pathway. In the former case, in one experiment, stimulation was made in the pyramid between lesions 3 and 4 (double pyramidal lesion). In case of cPyr stimulation, lesions 1 and 2 were added sequentially in order to investigate if the corticospinal excitation was mediated via C3-C4 PNs. All lesions were made mechanically, except lesion 2 which in some of the experiments was performed by reversible cooling. 3. Stimulation in the pyramid rostral to lesion 3 and in between lesions 3 and 4 evoked disynaptic EPSPs in the long PNs, which shows that they were mediated via reticulospinal neurones. Stimulation in cPyr after lesion 3 elicited disynaptic EPSPs, which remained after lesion 1 but were abolished after adding lesion 2. It is concluded that the disynaptic cPyr EPSPs were mediated via intercalated neurones in the C3-C4 segments. 4. When the disynaptic cPyr EPSP was conditioned with a single volley in nucleus ruber and/or in tectum, it was markedly facilitated, especially when the conditioned volley was applied simultaneously with the effective cPyr volley. The results show that the intercalated neurones in the C3-C4 segments receive monosynaptic convergence from cortico-, rubro- and tectospinal fibres. Stimulation in the lateral reticular nucleus (LRN) evoked monosynaptic EPSPs.(ABSTRACT TRUNCATED AT 400 WORDS)
In order to test the working hypothesis that motor deficits after low pyramidotomy may be due to transection of the cortico-cuneate pathway, a low pyramidotomy was made 2-4 months after a C2 dorsal column (DC) transection and tested on forelimb target-reaching and food-taking. Since food-taking recovered faster than after pyramidotomy alone, it is inferred that the loss of food-taking after pyramidotomy without previous DC transection is due mainly to transection of the cortico-cuneate pathway which controls transmission from forelimb Ia afferents to the motor cortex. The dysmetria and dyscoordination of target-reaching, on the other hand, was similar whether or not the low pyramidotomy was made after a previous C2 DC transection. It is tentatively suggested that dysmetria and dyscoordination of target-reaching after pyramidotomy may be due to transection of the pathway from the motor cortex which controls spinocerebellar transmission by its effect on the lateral reticular nucleus.
The morphology of single C3-C4 propriospinal neurones (PNs) including the cell body, dendritic tree, axonal trajectory and the pattern of projection and termination of axonal collaterals in the C3-C4 segments was investigated by intra-somatic or intra-axonal injection of horseradish peroxidase. All the C3-C4 PNs could be antidromically activated from the lateral funicle in C6 and the lateral reticular nucleus but not from Th13. Another criterion was that they received monosynaptic excitation from corticospinal fibres in the contralateral pyramid. Twenty-four C3-C4 PNs were successfully stained. They were located in the lateral part of laminae VI-VIII except for two neurones which were located in lamina V and two in lamina IX. Five to eleven dendrites originated from the cell bodies and extended throughout laminae IV-VIII and even into the white matter in the transverse plane and up to 3 mm rostro-caudally. The axonal trajectory from the cell body was usually curved before reaching the lateral funicle. The bifurcation of the stem axon into a descending and an ascending branch was mostly observed in the white matter close to or at the border between the white and grey matter at the level of the cell body. The ascending and descending axonal branches maintained their location in the same part of the lateral funicle. Sixteen out of 24 stem axons gave off collaterals in the grey matter and/or in the white matter. One to five collaterals were given off from the axons in the grey matter.(ABSTRACT TRUNCATED AT 250 WORDS)
Collateralization and termination of single C3-C4 propriospinal neurones (PNs) have been studied in the C6-Th1 segments of the cat using two methods: threshold mapping for antidromic activation of C3-C4 PNs and intra-axonal injection of horseradish peroxidase. Low threshold points for antidromic activation of C3-C4 PNs were found in the region of different motor nuclei in lamina IX both at one level and at different segmental levels, in all parts of lamina VII, in the lateral part of lamina VI and in the dorsal and ventral parts of lamina VIII. Collaterals were found from C6 to Th1. A marked decrease of conduction velocity of the stem axon occurred in the caudal region of termination, while it was almost constant in the rostral region of termination. HRP was injected iontophoretically in C6-Th1 into stem axons of neurones, which were activated antidromically from the ventral part of the lateral funiculus in C5/C6, from the lateral reticular nucleus (LRN) and monosynaptically from the corticospinal fibres (stimulated in the contralateral pyramid) which were transected in C5/C6. Reconstruction of successfully stained stem axons, revealed collaterals with terminals on presumed motoneurones in different parts of lamina IX and on interneurones in laminae IV-VIII. These findings confirm previous results which showed monosynaptic projections from C3-C4 PNs to forelimb motoneurones and Ia inhibitory interneurones. With respect to termination in the region of the motoneurones in lamina IX and in the region of Ia inhibitory interneurones in lamina VII, three patterns were found: 1) termination mainly in lamina IX (n = 1) 2) termination in laminae IX and VII (n = 15) and 3) termination mainly in lamina VII (n = 2). However, in some cases the same stem axon gave off collaterals which terminated either on motoneurones in lamina IX or on presumed Ia inhibitory interneurones in lamina VII. Furthermore, when the stem axons had collaterals which terminated in different motor nuclei only some of these collaterals had additional terminations on presumed Ia inhibitory interneurones. This result suggest that C3-C4 PNs do not follow a strict Ia pattern of reciprocal innervation. It is tentatively proposed that the difference of innervation may be related to the type of multi-joint movement, such as target-reaching with the forelimb, which has been shown to be controlled by the C3-C4 PNs. Termination in laminae VI, VIII and different parts of lamina VII indicates that C3-C4 PNs also project to other types of neurones than motoneurones and Ia inhibitory interneurones.(ABSTRACT TRUNCATED AT 400 WORDS)
Extra- and intracellular recording was made from neurones in laminae VII and VIII of the C6-Th1 segments, which were disynaptically excited from the contralateral pyramid, nucleus ruber and monosynaptically from the ipsilateral lateral reticular nucleus. The results suggest collateral excitation from the C3-C4 propriospinal neurones which are excited monosynaptically from the former two inputs and antidromically from the latter nucleus. The cells were antidromically activated from the ipsilateral nucleus fastigus, and from the ipsilateral or contralateral reticular formation. Some of the spinocerebellar and spinoreticular neurones were also antidromatically activated from Th13. It is suggested that spinocerebellar, spinoreticular and bifurcating spinocerebellar and spinoreticular neurones receive collateral input from the same excitatory C3-C4 propriospinal neurones which project to motoneurones and/or Ia inhibitory interneurones.
Intracellular recording and injection of horseradish peroxidase (HRP) were made in neurones located medially in lamina VII and in lamina VIII of the forelimb segments (C6-Th1). The cells received disynaptic excitation from the contralateral pyramid after corticospinal transection in C5/C6 and monosynaptic excitation from the ipsilateral lateral reticular nucleus. The pyramidal excitation was facilitated by a conditioning volley evoked from the contralateral nucleus ruber, which suggests convergence of cortico- and rubrospinal fibres on the intercalated neurones. It is proposed that laminae VII and VIII neurones receive a collateral input from the same excitatory C3-C4 propriospinal neurones which project to motoneurones and/or Ia inhibitory interneurones. Reconstruction of HRP-stained lamina VII and VIII neurones revealed ipsi- and contralateral ascending and/or descending axonal projections and termination in laminae VII and VIII in the forelimb segments.
Complete transection of the pyramid just rostral to the crossing gave defects in forelimb target-reaching and food-taking tested with retrieval of food from a cylinder. The most marked symptoms were dysmetria, dyscoordination of movement and almost total loss of the food-taking movement. Gradual recovery occurred, but even after 3-4 months the food-taking movement was deficient. The symptoms were less severe than those previously found after a high pyramidotomy but much more pronounced than those observed after complete transection of the corticospinal tract in the spinal cord. The motor defects after a low pyramidotomy closely resemble those found after a high dorsal column transection. It is tentatively proposed that the motor defects after low pyramidotomy are largely due to transection of corticocuneate fibers which regulate the feedback pathway from forelimb afferents to the motor cortex.
Wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP) was injected in the nerve branches to the spino- and acromiodeltoid muscles. After injection, the cats were awake for a period of 100 h during which they performed target-reaching and/or walking movements. Transneuronally labelled neurones were found in the nucleus raphe pallidus, in the magno- and gigantocellular parts of the medial reticular formation. All neurones were located between the level of the obex and 6 mm rostrally of the obex. These results demonstrate that medullary raphespinal and reticulospinal neurones have monosynaptic connexions with deltoid motoneurones. The raphespinal projection is partly from neurones with large cell bodies assumed to be non-monoaminergic.