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Activity evoked in the brain stem by stimulation of C fibres in the cervical vagus nerve of the dog
436
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Activity evoked in the, brain stem by stimulation of C fibres in the cervical vagus nerve of the dog
1 F. FUSSEY*, C KIDD AND J G WHITWAM** Cardtovmcular Untt, Depa~tment o/Phvstoh~g3, Umver~tO' of Leeds, Leeds 2 (Great Brttam)
(Accepted October 12th, 1972)
The cervical vagus nerve consists predominantly of C fibres; myelinated fibres contribute less than 20 o, to the total n u m b e r of fibres present 1,6,11. Previous reports of" vagal evoked activity in the medulla from elecmcal stamulation either have not included activity with latencies appropriate to C fibre actlvatloff'nJ, 19 or have involved the use o f coarse mlcroelectrodes which precluded discrete locahzation ~lthm the brain stem tv. In the present invesUgatlon 'multiple' and 'single unit' responses evoked by electrical stimulation of the intact lpsilateral cervical vagus nerve were recorded from medullary neural elements Evoked responses associated with C fibre acuvation were extensively represented m areas of the dorsal medulla and some of their characterlstlcs are described Experiments were performed on dogs anaesthetized with a single intravenous injection of thiopentone sodium (40 mg/kg) followed by ventilation with a nitrous oxide-oxygen mixture (70-80 °.,,/30-20 °.o) and immobdized with intermittent doses of succinylchohne ( I-2 mg/kg/h) Arterial pH, Pcoz and Po,, were intermittently measured and maintained wlthin normal hmits by the administration of s o d m m N c a r b o n a t e solution and changes in ventdatmn or inspired oxygen concentration as appropriate. Oesophageal temperature was maintained within the range 37-39 ~C. The medulla was exposed through a posterior craniotomy and the cerebellum retracted. Extracellular recordings were made with glass insulated platinum microelectrodes 8 connected wa a cathode follower to a Tektronix 122 preamphfier, w~th its tow and high pass filters ~ct at 80 Hz and 10 kHz respectively, and displayed on a Tektronix 565 oscdloscope Monophaslc square-wave smnuh were delivered to the desheathed intact cervical vagus wa bipolar Ag AgCI wire electrodes; the nerve was not cut in order to retain spontaneous activity and the temperature was maintained m the range 35 38 "C m ~ paraffin pool. In 87",, of I04 penetratmns, which traversed the regmn of the nucleus tractus * Present address. Department of Surgery, Umverslty of Sheffield, The Royal Infirmary, Sheffield $6 3DA, Great Britain ** Present address : Department of Anaesthetics, Royal Postgraduate MedlcalSchool, Ducane Road~ London W 12, Great Britain
437
SHORT COMMUNICATIONS
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I
lOOmsec Fig. 1. Diagrammatic representation of dog medulla (0.5-1.0 mm rostral to obex). Vertical bars' dorsoventral llmnts of late responses. Shaded area: region with intermediate latency responses. A, Evoked responses from dorsal zone. B, Evoked unit responses from ventral zone 4, stimulus artefact; DCN, dorsal column nuclei, NTS, nucleus tractus sohtarius; DMVN, dorsal motor vagal nucleus, NI, nucleus mtercalatus; XII, XII nerve nucleus.
solitarius (NTS) and dorsal motor vagal nucleus (DMVN), responses were recorded with latencies between 80 and 170 msec (Fig. 1). The responses obtained from the dorsal and ventral parts of this region showed certain differences. Dorsally, the evoked response consisted of a 'mass discharge" of small amplitude spikes superimposed upon a slow wave (Fig. I A). Within the dorsal region the long latency responses were clearly separate from an earlier evoked respone (mean initial latency 4 msec) 9. During the experiments, the intensity of vagal stimuli required to evoke the dorsal responses was consistent with that required to activate C fibresL In two experiments recordings were made of fibre activity in the divided vagus nerve immediately after recording the central responses; the thresholds of the vagal C potential and the centrally evoked responses coincided. The initial latencies of the dorsal 'mass' responses when related to the vagus nerve conduction distances were consistent with activity evoked in C fibres with a mean calculated conduction velocity of 1.45 m/sec. From these observations it was concluded that the dorsal 'mass' response resulted from the activation of vagal C fibres. The dorsal responses, however, could not be identified with any obvious associated spontaneous spike activity 9,1° and may have been recorded from primary afferent C fibres, interneurones activated via C fibres or efferent C fibres or neurones. The dorsal responses extended from just below the region of units showing dorsal column characteristics and merged ventrally, with the long latency responses from the ventral region. From the ventral part of the region the response consisted mainly of larger
438
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Number
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Velocity
26
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34
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Fig, 2 Histogram of calculated conductk)n ~eloc~t~es of 45 single umts.
amphtude spikes (Fig. t B) from which "single unit' recordings were obtained. These long latency single unit responses were recorded in association with evoked umt responses of latencles m the range 17-80 msec 9 (Fig IB). Units, in this zone, discharged with low frequency irregular patterns and often showed long latency evoked spikes. However, a supra-threshold vagal stimulus, the intensity of which was consistent with C fibre activauon v, invariably evoked single spikes from the units. The mean latency of 45 such units was 96.5 msec (range 31 6-144.8) and was assocmted with a mean vagal conduction distance of 119.7 mm (range 100-142). The calculated conduction velocity for each unit (Fig. 2) gave a mean value of 1.4 m/sec (range 0.85-3.19) which was within the range of C fibre conduction velocities16, is. The 4 units with conduction velocities greater than 2.5 m/sec may have represented fibres which were myehnated over part of their course In the vagus nerve I6. Criteria previously used to establish the synaptlc connections of single unlts~ are not applicable to C fibre units. However, more than 50 °,o of these evoked single umts were identified with spontaneously active units (low frequency irregular pattern) and 16 of these umts showed no evoked spike when a spontaneous spike preceded the anticipated evoked spike although the evoked spike probability was otherwise units. In the case of these umts, a spontaneous spike collided with an evoked spike when the former arose at any point during the evoked spike latency, t.e. approximately 0-t00 msec before the anticipated evoked spike: the most probable explanation of this effect was that the units were spontaneously active vagal efferent neurones. For other spontaneously active evoked units, spikes were sometimes observed during this interval but the evoked sp~ke persisted. There are a number of possible explanations for the latter observatmn, for example, these spontaneous sp~kes may have arisen from a unit
SHORT COMMUNICATIONS
439
other than the evoked one or the units may have been evoked via afferent fibres in the vagus nerve. Fig. 1 shows a diagrammatic section of the dog medulla (,0.5-1.0 mm rostral to obex) on which the location of the responses is indicated; the dorsoventral limits of the late responses are approximately indicated by vertical bars. The shaded area indicates the region from which responses with latencies in the range 17-80 m/sec were found in addmon to late responsesL Responses were consistently recorded from the nucleus tractus sohtarlus. The ventral zone of the responses, where the single umts were recorded, extended into the dorsal motor vagal nucleus but did not involve the nucleus intercalatus. Responses were recorded in a region extending from 1 mm caudal to obex, to 3-4 mm rostral to obex. Lam and Tyler 17 recorded, in the region of nucleus tractus sohtarJus, slow wave responses of latencies appropriate to C fibre activation following stimulation of the cervical vagus nerve of the rabbit and noted a dorsoventral change in the polarity of the responses as the region was traversed. The present results clearly show a dorsoventral differentiation of the responses to stimulation of vagal C fibres recorded in the nucleus tractus solitarius and dorsal motor vagal nucleus. Degeneration stu&es have shown that the nucleus tractus sohtarius ~s a major s~te of vagal afferent termination and have usually shown no afferent termination in the dorsal motor vagal nucleus 3-'~, but vagal efferent fibres have been shown to arise from this nucleus 11,I',1'5. In the present study, the single units were recorded from the ventral part of the responsive zone which included the dorsal motor vagal nucleus. Also, since it was improbable that primary afferent C fibre terminals were frequently recorded as single umts and s~nce the recorded units showed collision of evoked and spontaneous spikes, it is concluded that the dorsal motor vagal nucleus Is a source of the efferent C fibres m the vagus nerve. Histological evidence for efferent C fibres in the vagus nerves has been prewously reported 1. The failure of previous workers 14,'° to activate neurones of the dorsal motor nucleus antldromically may have resulted from collision of the evoked spikes with ongoing spontaneous spikes or from using stimulus intensities too low to excite C fibres in the vagus nerve. This work was supported by the British Heart Foundation, the Medical Research Council and the Wellcome Trust. The authors are indebted to Mrs. Barbara Royle for histological services, and Miss Christine Coates and Mr. Michael Gould for techmcal assistance.
I AGOSTINI, E., CHINNOCK, J. E., DE BURGH DALY, M. C , AND MURRAY, J. G., Functional and hlstologmal studies of the vagus nerve and its branches to the heart, lungs and abdominal viscera m the cat, J Physiol. (Lond.), 135 (1957) 182-205. 2 ANDERSON,F D., AND BERRY, C. M., An oscillograph study of the central pathways of the vagus nerve in the cat, J comp. Neurol., 106 (1956) 163-181. CAJAL, S RAMdN Y, Ht~tologie du Systdme Nerveu,c de l ' H o m m e et des Vertdbr~, Vol 1, Malolne, Paris, 1909 4 COTTLE, M K , Degeneration studies of primary afferents of IX and X cranial nerves m the cat, J. comp Neurol , 122 (1964) 329-345.
440
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5 FOLEY, J. O , AND DUBBOIS, F S , An experimental study ot the rootlets o f the ~agus n m x e m ih~ cat, J. comp Neurol, 60 (1934) 137-159 6 FOLEY, J O , AND DUBBOIS, F S , Q u a n t l t a t w e studies o f the vagus nerve m the cat I The J Jr.,, ,q s e n s o r y to m o t o r fibres, J ~omp Neurol, 67 (1937) 49-64 7 FUSSEY, !. F , KIDD, C , A"413 WHIT\V,kM, J (~ , Evoked activity in sympathetic n e l v e s m ~e~pem,,c to peripheral nerve s t i m u l a t i o n In the dog, J Phystol (Lond), 200 (1968) 77 78P. 8 FUSSE~,, 1 F , KIt)D, IS' , ANt) W H I F \ V A M , J G , T h e dttterentlallon o f axonal a n d s o m a - d e n d , tt~c spike activity, Pfluger,s Arch sea P h w t o l , 321 (1970) 283-292 9 FOSSE~, I F., KinD, C , Ar~I~Wr~rrwAM, J G., Evoked r e s p o n s e s in the brain-stem mcdlated b~ ~, fibres In the cervical vagus nerve, in preparation I0 FUssI:Y, 1 F., KIDD, C , AND "gCHIJWad',l,J. G . C a r d i o v a s c u l a r m t e r n e u r o n e s m the brain-stem ,~1 the dog, in preparation 11 GASKLLL, W. H , O n the atructure, dlstllbutlon a n d function o f the nerves v, hlch i n n e r \ a t e the visceral and vascular ~ystems, J Phystol t Lond ), 7 (1886) 1-80 12 G~TZ, B , AND SIRNIS, T , T h e l o c a h z a u o n within the dorsal m o t o r vagal nucleus, J ',~.;t' Neurol, 90 (1949) 95- I 10 13 HARRISON, F , AND Be.ULSH, S. R , l n t r a m e d u l l a r y potentials following s t m m l a t l o n o f the cer,.ivat vagus, 4nat Rec.. 91 (1945) 280 14 HIGGS, B., AND KEgR, E W L., U n p u b l i s h e d observation, q u o t e d m E W I_ K~l~u Preserved vagal v l s c e r o m o t o r function following destruction o f the dorsal m o t o r nucleus. J Physiol. (Lond.), 202 (1969) 755-769 15 HUSTEN, K . , Experlmentelle U n t e r s u c h u n g e n uber dm Bezlehungen der Vaguskerne zu den Brustu n d B a u c h - o r g a n e n , Z ges. Neutol Psvchlat., 93 (1924) 763-773. 16 IGGO, A ~T h e electrophyslologlcal identification o f single nerve fibres, with particular reference to the slowest-conducting vagal afferent fibres m the cat, J Physlol (Lord.), 142 (1958) 110 126 17 LAM, R L , AND TYLER, H R., Electrical responses evoked m the visceral afferent nucleus ot file rabbit by vagal stunulatlon, J ~omp N e w o l , 97 (1952) 21-36 18 PAINTAL, A S., A c o m p a m o n o f the nerve impulses o f m a m m a h a n n o n - m e d u l l a t e d nerve fibres with those o f the smallest d i a m e t e r m e d u l l a t e d fibres. J Physiol. (Lond), 193 (1967) 523 533 19 PORTER, R , Unit l e s p o n s e s evoked m the medulla o b l o n g a t a by vagus nerve stimulation J Phvstol (L,o~td), 168 ( 1963 } 717- 735 20 URABE, M C , AND FSUBOK~,WA, T , D~strlbutlon o f actwatlng n e u r o n s in medulla o b l o n g a t a by stimulation o f the vagus nerve, Neurol. reed Chtr, 2 (1960) 147-161.
Btam
Else~lc~ ScmntllJ~ [ ' u b h q l m g ( ~ m l p , m s . A m s t e r d a m
Reseatctr
~*) ~ t ) / ~ j
+ ,~ . . . .
~
P r m t e d . H Tl,t Netl~t,'.~. I
Activity evoked in the, brain stem by stimulation of C fibres in the cervical vagus nerve of the dog
1 F. FUSSEY*, C KIDD AND J G WHITWAM** Cardtovmcular Untt, Depa~tment o/Phvstoh~g3, Umver~tO' of Leeds, Leeds 2 (Great Brttam)
(Accepted October 12th, 1972)
The cervical vagus nerve consists predominantly of C fibres; myelinated fibres contribute less than 20 o, to the total n u m b e r of fibres present 1,6,11. Previous reports of" vagal evoked activity in the medulla from elecmcal stamulation either have not included activity with latencies appropriate to C fibre actlvatloff'nJ, 19 or have involved the use o f coarse mlcroelectrodes which precluded discrete locahzation ~lthm the brain stem tv. In the present invesUgatlon 'multiple' and 'single unit' responses evoked by electrical stimulation of the intact lpsilateral cervical vagus nerve were recorded from medullary neural elements Evoked responses associated with C fibre acuvation were extensively represented m areas of the dorsal medulla and some of their characterlstlcs are described Experiments were performed on dogs anaesthetized with a single intravenous injection of thiopentone sodium (40 mg/kg) followed by ventilation with a nitrous oxide-oxygen mixture (70-80 °.,,/30-20 °.o) and immobdized with intermittent doses of succinylchohne ( I-2 mg/kg/h) Arterial pH, Pcoz and Po,, were intermittently measured and maintained wlthin normal hmits by the administration of s o d m m N c a r b o n a t e solution and changes in ventdatmn or inspired oxygen concentration as appropriate. Oesophageal temperature was maintained within the range 37-39 ~C. The medulla was exposed through a posterior craniotomy and the cerebellum retracted. Extracellular recordings were made with glass insulated platinum microelectrodes 8 connected wa a cathode follower to a Tektronix 122 preamphfier, w~th its tow and high pass filters ~ct at 80 Hz and 10 kHz respectively, and displayed on a Tektronix 565 oscdloscope Monophaslc square-wave smnuh were delivered to the desheathed intact cervical vagus wa bipolar Ag AgCI wire electrodes; the nerve was not cut in order to retain spontaneous activity and the temperature was maintained m the range 35 38 "C m ~ paraffin pool. In 87",, of I04 penetratmns, which traversed the regmn of the nucleus tractus * Present address. Department of Surgery, Umverslty of Sheffield, The Royal Infirmary, Sheffield $6 3DA, Great Britain ** Present address : Department of Anaesthetics, Royal Postgraduate MedlcalSchool, Ducane Road~ London W 12, Great Britain
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SHORT COMMUNICATIONS
I
I
lOOmsec Fig. 1. Diagrammatic representation of dog medulla (0.5-1.0 mm rostral to obex). Vertical bars' dorsoventral llmnts of late responses. Shaded area: region with intermediate latency responses. A, Evoked responses from dorsal zone. B, Evoked unit responses from ventral zone 4, stimulus artefact; DCN, dorsal column nuclei, NTS, nucleus tractus sohtarius; DMVN, dorsal motor vagal nucleus, NI, nucleus mtercalatus; XII, XII nerve nucleus.
solitarius (NTS) and dorsal motor vagal nucleus (DMVN), responses were recorded with latencies between 80 and 170 msec (Fig. 1). The responses obtained from the dorsal and ventral parts of this region showed certain differences. Dorsally, the evoked response consisted of a 'mass discharge" of small amplitude spikes superimposed upon a slow wave (Fig. I A). Within the dorsal region the long latency responses were clearly separate from an earlier evoked respone (mean initial latency 4 msec) 9. During the experiments, the intensity of vagal stimuli required to evoke the dorsal responses was consistent with that required to activate C fibresL In two experiments recordings were made of fibre activity in the divided vagus nerve immediately after recording the central responses; the thresholds of the vagal C potential and the centrally evoked responses coincided. The initial latencies of the dorsal 'mass' responses when related to the vagus nerve conduction distances were consistent with activity evoked in C fibres with a mean calculated conduction velocity of 1.45 m/sec. From these observations it was concluded that the dorsal 'mass' response resulted from the activation of vagal C fibres. The dorsal responses, however, could not be identified with any obvious associated spontaneous spike activity 9,1° and may have been recorded from primary afferent C fibres, interneurones activated via C fibres or efferent C fibres or neurones. The dorsal responses extended from just below the region of units showing dorsal column characteristics and merged ventrally, with the long latency responses from the ventral region. From the ventral part of the region the response consisted mainly of larger
438
SItOtll
(
()MMI~51( ,~,|t,~
,
Number
of U n d s
t4 t2
tO
0'6
10
t4
1'8
2'2
Calculated
Conduct)on
Velocity
26
3'0
34
mlsec
Fig, 2 Histogram of calculated conductk)n ~eloc~t~es of 45 single umts.
amphtude spikes (Fig. t B) from which "single unit' recordings were obtained. These long latency single unit responses were recorded in association with evoked umt responses of latencles m the range 17-80 msec 9 (Fig IB). Units, in this zone, discharged with low frequency irregular patterns and often showed long latency evoked spikes. However, a supra-threshold vagal stimulus, the intensity of which was consistent with C fibre activauon v, invariably evoked single spikes from the units. The mean latency of 45 such units was 96.5 msec (range 31 6-144.8) and was assocmted with a mean vagal conduction distance of 119.7 mm (range 100-142). The calculated conduction velocity for each unit (Fig. 2) gave a mean value of 1.4 m/sec (range 0.85-3.19) which was within the range of C fibre conduction velocities16, is. The 4 units with conduction velocities greater than 2.5 m/sec may have represented fibres which were myehnated over part of their course In the vagus nerve I6. Criteria previously used to establish the synaptlc connections of single unlts~ are not applicable to C fibre units. However, more than 50 °,o of these evoked single umts were identified with spontaneously active units (low frequency irregular pattern) and 16 of these umts showed no evoked spike when a spontaneous spike preceded the anticipated evoked spike although the evoked spike probability was otherwise units. In the case of these umts, a spontaneous spike collided with an evoked spike when the former arose at any point during the evoked spike latency, t.e. approximately 0-t00 msec before the anticipated evoked spike: the most probable explanation of this effect was that the units were spontaneously active vagal efferent neurones. For other spontaneously active evoked units, spikes were sometimes observed during this interval but the evoked sp~ke persisted. There are a number of possible explanations for the latter observatmn, for example, these spontaneous sp~kes may have arisen from a unit
SHORT COMMUNICATIONS
439
other than the evoked one or the units may have been evoked via afferent fibres in the vagus nerve. Fig. 1 shows a diagrammatic section of the dog medulla (,0.5-1.0 mm rostral to obex) on which the location of the responses is indicated; the dorsoventral limits of the late responses are approximately indicated by vertical bars. The shaded area indicates the region from which responses with latencies in the range 17-80 m/sec were found in addmon to late responsesL Responses were consistently recorded from the nucleus tractus sohtarlus. The ventral zone of the responses, where the single umts were recorded, extended into the dorsal motor vagal nucleus but did not involve the nucleus intercalatus. Responses were recorded in a region extending from 1 mm caudal to obex, to 3-4 mm rostral to obex. Lam and Tyler 17 recorded, in the region of nucleus tractus sohtarJus, slow wave responses of latencies appropriate to C fibre activation following stimulation of the cervical vagus nerve of the rabbit and noted a dorsoventral change in the polarity of the responses as the region was traversed. The present results clearly show a dorsoventral differentiation of the responses to stimulation of vagal C fibres recorded in the nucleus tractus solitarius and dorsal motor vagal nucleus. Degeneration stu&es have shown that the nucleus tractus sohtarius ~s a major s~te of vagal afferent termination and have usually shown no afferent termination in the dorsal motor vagal nucleus 3-'~, but vagal efferent fibres have been shown to arise from this nucleus 11,I',1'5. In the present study, the single units were recorded from the ventral part of the responsive zone which included the dorsal motor vagal nucleus. Also, since it was improbable that primary afferent C fibre terminals were frequently recorded as single umts and s~nce the recorded units showed collision of evoked and spontaneous spikes, it is concluded that the dorsal motor vagal nucleus Is a source of the efferent C fibres m the vagus nerve. Histological evidence for efferent C fibres in the vagus nerves has been prewously reported 1. The failure of previous workers 14,'° to activate neurones of the dorsal motor nucleus antldromically may have resulted from collision of the evoked spikes with ongoing spontaneous spikes or from using stimulus intensities too low to excite C fibres in the vagus nerve. This work was supported by the British Heart Foundation, the Medical Research Council and the Wellcome Trust. The authors are indebted to Mrs. Barbara Royle for histological services, and Miss Christine Coates and Mr. Michael Gould for techmcal assistance.
I AGOSTINI, E., CHINNOCK, J. E., DE BURGH DALY, M. C , AND MURRAY, J. G., Functional and hlstologmal studies of the vagus nerve and its branches to the heart, lungs and abdominal viscera m the cat, J Physiol. (Lond.), 135 (1957) 182-205. 2 ANDERSON,F D., AND BERRY, C. M., An oscillograph study of the central pathways of the vagus nerve in the cat, J comp. Neurol., 106 (1956) 163-181. CAJAL, S RAMdN Y, Ht~tologie du Systdme Nerveu,c de l ' H o m m e et des Vertdbr~, Vol 1, Malolne, Paris, 1909 4 COTTLE, M K , Degeneration studies of primary afferents of IX and X cranial nerves m the cat, J. comp Neurol , 122 (1964) 329-345.
440
SHOR1 ~ ¢tMMUNV'~,~lf~N',
5 FOLEY, J. O , AND DUBBOIS, F S , An experimental study ot the rootlets o f the ~agus n m x e m ih~ cat, J. comp Neurol, 60 (1934) 137-159 6 FOLEY, J O , AND DUBBOIS, F S , Q u a n t l t a t w e studies o f the vagus nerve m the cat I The J Jr.,, ,q s e n s o r y to m o t o r fibres, J ~omp Neurol, 67 (1937) 49-64 7 FUSSEY, !. F , KIDD, C , A"413 WHIT\V,kM, J (~ , Evoked activity in sympathetic n e l v e s m ~e~pem,,c to peripheral nerve s t i m u l a t i o n In the dog, J Phystol (Lond), 200 (1968) 77 78P. 8 FUSSE~,, 1 F , KIt)D, IS' , ANt) W H I F \ V A M , J G , T h e dttterentlallon o f axonal a n d s o m a - d e n d , tt~c spike activity, Pfluger,s Arch sea P h w t o l , 321 (1970) 283-292 9 FOSSE~, I F., KinD, C , Ar~I~Wr~rrwAM, J G., Evoked r e s p o n s e s in the brain-stem mcdlated b~ ~, fibres In the cervical vagus nerve, in preparation I0 FUssI:Y, 1 F., KIDD, C , AND "gCHIJWad',l,J. G . C a r d i o v a s c u l a r m t e r n e u r o n e s m the brain-stem ,~1 the dog, in preparation 11 GASKLLL, W. H , O n the atructure, dlstllbutlon a n d function o f the nerves v, hlch i n n e r \ a t e the visceral and vascular ~ystems, J Phystol t Lond ), 7 (1886) 1-80 12 G~TZ, B , AND SIRNIS, T , T h e l o c a h z a u o n within the dorsal m o t o r vagal nucleus, J ',~.;t' Neurol, 90 (1949) 95- I 10 13 HARRISON, F , AND Be.ULSH, S. R , l n t r a m e d u l l a r y potentials following s t m m l a t l o n o f the cer,.ivat vagus, 4nat Rec.. 91 (1945) 280 14 HIGGS, B., AND KEgR, E W L., U n p u b l i s h e d observation, q u o t e d m E W I_ K~l~u Preserved vagal v l s c e r o m o t o r function following destruction o f the dorsal m o t o r nucleus. J Physiol. (Lond.), 202 (1969) 755-769 15 HUSTEN, K . , Experlmentelle U n t e r s u c h u n g e n uber dm Bezlehungen der Vaguskerne zu den Brustu n d B a u c h - o r g a n e n , Z ges. Neutol Psvchlat., 93 (1924) 763-773. 16 IGGO, A ~T h e electrophyslologlcal identification o f single nerve fibres, with particular reference to the slowest-conducting vagal afferent fibres m the cat, J Physlol (Lord.), 142 (1958) 110 126 17 LAM, R L , AND TYLER, H R., Electrical responses evoked m the visceral afferent nucleus ot file rabbit by vagal stunulatlon, J ~omp N e w o l , 97 (1952) 21-36 18 PAINTAL, A S., A c o m p a m o n o f the nerve impulses o f m a m m a h a n n o n - m e d u l l a t e d nerve fibres with those o f the smallest d i a m e t e r m e d u l l a t e d fibres. J Physiol. (Lond), 193 (1967) 523 533 19 PORTER, R , Unit l e s p o n s e s evoked m the medulla o b l o n g a t a by vagus nerve stimulation J Phvstol (L,o~td), 168 ( 1963 } 717- 735 20 URABE, M C , AND FSUBOK~,WA, T , D~strlbutlon o f actwatlng n e u r o n s in medulla o b l o n g a t a by stimulation o f the vagus nerve, Neurol. reed Chtr, 2 (1960) 147-161.