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Hepatic sodium and osmoreceptors activate neurons in the ventrobasal thalamus
398
Brain Research, 168 (1979) 398-403 © Elsevier/North-Holland BiomedicalPress
Hepatic sodium and osmoreceptors activate neurons in the ventrobasal thalamus
RICHARD C. ROGERS, DONALD NOVIN and LARRY L. BUTCHER Brain Research Institute and Department of Psychology, University of California, Los Angeles, Calif. 90024 (U.S.A.)
(Accepted January 25th, 1979)
Electrophysiological studies of multifiber preparations of the hepatic branch of the vagus nerve in rats and rabbits have indicated the presence of hepatic sodium receptors and osmoreceptors 1,8. These hepatovagal signals have a significant effect on physiological mechanisms concerned with osmoregulation. In rats, changes in urine volume follow changes in hepatic osmolarity more closely than changes in systemic osmolarity. That is, simultaneous infusions of hypertonic saline into the vena cava and water into the hepatic portal vein produced a prompt and copious diuresis whereas a reversal of the infusion pattern produced antidiuresislL Resection of the hepatic branch of the vagus eliminated this hepatically mediated effect8. The hepatic receptor inputs affect behavioral osmoregulation also, since hepaticportal infusions of inhibitors of the electrogenic sodium-potassium pump (sodium chloride, Ouabain) shift the normally strong saline taste preference of the rat toward rejection. Venous infusions of the same agents were without effect. Right cervical vagotomy eliminates this hepatically mediated preference shift 4. The central neural structures that relay these hepatovagal signals were not known with any certainty until recently, but anatomical 2,~s,14,1a, and neurophysiologica15,~5,18 studies point to a pathway closely paralleling the central gustatory system. Anatomical and indirect neurophysiological evidence supports the notion that vagal afferents terminate in the nucleus of the solitary tract (NTS). NTS neurons then project to the pontine parabrachial nucleus whose axons bifurcate, one branch projecting dorsally to the somatosensory segment of the ventral thalamus and the other projecting to the hypothalamus and amygdala. Although cells scattered throughout the diencephalon respond to portal infusions of saline and glucose is, no firm conclusions have been made regarding the afferent projections to those cells. However, the studies reported here provide perhaps the first physiological and anatomical verification of hepatovagal afferent flow through the dorsal part of the gustatory pathway. Rats anesthetized with urethane (1.5 g/kg) were provided with both inferior vena cava and hepatic portal cannulae. After mounting the rat in the stereotaxic frame the
399
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Fig. 1. Typical responses of hepatically activated VPM units. A: record of firing rate vs time and infusion condition. VPM neuron activated by hepatic water infusions, inhibited generally by hepatic hyperosmotic solutions. Note inhibition of water activation by preceding infusion of hypertonic sodium chloride. Abbreviations: vw, vena cava water; hw, hepatic water; hs, hepatic 0.3 M sodium chloride; hm, hepatic 0.6 M mannose; hg, hepatic 0.6 M glucose; and hu, hepatic 0.6 M sucrose. Infusion vol. 0.15 ml in all cases. B: VPM unit was activated only by hepatic infusions of sodium chloride and choline chloride. Infusion vol. was 0.15 ml for all cases. Abbreviations: hs, hepatic 0.3 M sodium chloride; vs, vena cava 0.3 M sodium chloride; vw, vena cava water; hk hepatic 0.3 M potassium chloride; hm, hepatic 0.6 M mannose; and hc, hepatic 0.3 M choline chloride. Calibration bars, 30 spikes/see, 5 min. cannulae were attached to syringes containing either pure water or 0.3 M sodium chloride. Double-barreled glass microelectrodes with a tip diameter o f between 1 and 5 # m filled with 0.2 Tris buffer (pH 8.6) and 5 % horseradish peroxidase (HRP, Sigma type VI) and a 4 % Pontamine, 5 % potassium chloride solution were lowered through a trephination to recording sites in the brain via hydraulic microdrivea. Recording t h r o u g h the Pontamine electrode, single-unit records were displayed oscillographically, and firing rate was constantly monitored with a Schmitt-trigger and pulse integrator-polygraph apparatus. After isolating a suitable neuron, small a m o u n t s (0.1-0.2 ml) o f hypertonic saline were infused into the hepatic portal while at the same time, water was infused into the vena cava. This simultaneous infusion paradigm
400
Fig. 2. Typical results of a small H R P injection into the VPM. A: large arrow indicates a typical small injection into hepatically activated site in the dorsal VPM. Small arrow indicates 'unsuccessful' electrode track. Abbreviations; mmt, mammilothalamic tract; ml, medial lemniscus; ic, internal capsule; and v, third ventricle. Calibration bar, 500/~m. B: large arrow indicates HRP-labeled cell in the parabrachial nucleus resulting from the injection in A above. Small arrows indicate thionin-counterstained cells out of the plane of focus, Calibration bar, 15/~m.
401 prevented salt or water accumulation during the initial stages of the experiment as mixing of the two solutions in the proximal vena cava produced isotonic saline. The infusions were repeated in reverse order (ie. the vena cava received saline and the portal vein, water) when the cell's firing rate, post-infusion, returned to the preinfusion baseline. If a replicable and significant change in firing rate was observed following the infusions, 0.3 M sodium chloride or water solutions were applied to the portal or caval veins alone in order to determine which route produced the effect. If portal infusions alone affected the cell under examination, then a variety of solutions were portally infused to determine whether that cell responded to hepatic sodium alone or to hepatic osmotic stimulation. Mannitol, glucose and sucrose, all at a concentration of 0.6 M, were infused as a test for osmotically sensitive receptors while choline chloride and potassium chloride were used as non-sodium ionic stimuli. Following these procedures, very small amounts of HRP were electrophoretically applied to the recording site (2.5/~A positive DC applied for 2 rain producing an injection site less than 300/zm in diameter, including halo; current was applied longer to achieve larger injection sites). The positions of numerous non-hepatically driven neurons were likewise marked with Pontamine using negative DC. Twenty-four hours after HRP application the rats were perfused with a 0.1 M monobasic phosphate buffer solution (pH 7.4) followed by a solution of 1 ~ paraformaldehyde-3 ~ glutaraldehyde in phosphate buffer. The brains were removed, cut on a freezing microtome and treated for the demonstration of retrograde transport of HRP according to the method of De Olmos 7. Numerous ceils in or near the ventro-postero-medial nucleus of the thalamus (VPM) responded to hepatic portal infusions. The responses were of two general types. The first (Fig. 1A) type of neuronal unit responded only to hepatic infusions of sodium or choline chloride. Potassium chloride and non-ionic, hyperosmotic solutions were without effect. The second type of thalamic cell (Fig. 1B) responded to changes in portal osmolarity; ie. in this case the cell was inhibited by both ionic and non-ionic hyperosmotic solutions infused into the portal vein, but was activated by the presence of water in the hepatic portal. Anatomical segregation of the responses was not seen; both types of cells appeared evenly distributed throughout the VPM. Very small injections of HRP through the recording electrodes were often insufficient to demonstrate retrograde transport. However, in those cases where transport from hepatically activated areas was observed, cells in the parabrachial nuclei were always demonstrated (Fig. 2A, B). With larger injections cells in the principal trigeminal sensory nucleus, nucleus reticularis thalami, substantia nigra (pars reticulata), the nucleus gracilis and the dentate nucleus of the cerebellum were demonstrated. Projections from the principal trigeminal sensory nucleus, nucleus reticularis thalami and the substantia nigra are probably directed toward the VPM 8,17,t9 while demonstrations of projections from the nucleus gracilis and the dentate nucleus may have been the result of spread of HRP into the adjacent ventro-postero-lateral nucleus of the thalamusl0AL From these results it is apparent that osmoreceptors and sodium receptors in the liver activate neurons in the ventral sensory thalamus. Blake and Lin4 proposed that
402 activity o f the hepatic sodium receptor depends on the electrogenic sodium-potassium pump. The finding o f cells in the sensory thalamus that responded only to the presence of hepatic sodium and choline support their hypothesis as both ions inhibit the sodium-potassium p u m p 16. This inhibition would presumably depolarize nerve fibers in the liver thereby increasing their excitability 4. Portal infusions of potassium chloride had n o effect on V P M cells in our studies. This m a y be due to the activation of the electrogenic p u m p by the presence of potassium, which would cause receptor elements to hyperpolarize, reducing excitability 4. The demonstration o f another class of response, the hepatic osmoreceptor response, indicates that perhaps both a specific sodium receptor and an osmoreceptor m a y exist in the liver and that they share c o m m o n afferent projections. This finding o f two classes of hepatically activated thalamic neurons m a y help resolve some of the controversy with respect to the presence or absence of hepatic sodium receptors a,4 or osmoreceptors 1,11. H R P histochemistry supports the presumption that hepatovagal afferent pathways in the brain are, at least in part, parallel to a previously described gustatory afferent system that includes the nucleus of the solitary tract, the parabrachial nucleus and the ventrobasal thalamus. This work was supported by N I N C D S G r a n t NS 7687 to D. N. and U S P H S G r a n t NS 10928 to L.L.B. ; R.C.R. was supported by N I M H Pre-doctoral Fellowship M H06415. We thank K e n Hirabayashi for assistance with the H R P method and Gerlinda Rogers and K o n r a d Talbot for their assistance in the interpretation o f the material. 1 Adachi, A., Niijima, A. and Jacobs, H. L., A hepatic osmoreceptor mechanism in the rat: electrophysiological and behavioral studies, Amer. J. Physiol., 213 (1976) 1043-1049. 2 Allen, W. F., Origin and distribution of the tractus solitarius in the guinea pig, J. cornp. Neurol., 35 (1923) 171-204. 3 Andrews, W. H. H. and Ohrbach, J., Sodium receptors activating some nerves of perfused rabbit livers, Amer. J. Physiol., 227 (1974) 1273-1275. 4 Blake, W. D. and Lin, K. K., Effects of hepatic portal vein infusion of glucose and sodium solutions on the control of saline drinking in the rat, J. Physiol. (Lond.), 274 (1978) 129-139. 5 Dell, P. and Olson, R., Projections thalamiques, corticales et c6r6belleuses des afferences visc6rales vagales, C. R. Soc. Biol. (Paris), 145 (1951) 1084-1087. 6 Dennhardt, R., Ohm, W. W. and Haberich, F. J., Die Ausschaltung der Lebediste des N. vagus an der wachen Ratte und ihr einfluss auf hepatogene Diurese - - indirekter Bewis ffir die afferente Leitung der Leber-Osmoreceptoren fiber den N. Vagus, Pfliigers Arch. ges. PhysioL, 328 (1971) 51-56. 7 De Olmos, J. S., An improved HRP method for the study of central nervous connections, Exp. Brain Res., 29 (1978) 541-551. 8 Faull, R. L. M. and Carman, J. B., Ascending projections of the substantia nigra in the rat, J. comp. NeuroL, 132 (1968) 73-93. 9 Graybiel, A. M. and Devor, M., A microelectrode delivery technique for use with horseradish peroxidase, Brain Research, 68 (1974) 167-173. 10 Groenwegen, H. J., Boesten, A. J. P. and Voogd, J., The dorsal column nuclear projections to the nucleus ventralis posterior lateralis in the cat: an autoradiographic study, J. comp. Neurol., 162 (1975) 505-518. 11 Haberich, F. J., Osmoreception in the portal circulation, Fed. Proc., 27 (1968) 1137-1141. 12 Kalil, K., Topographic organization of projections from the dentate and interpositus nuclei in the rhesus monkey: an autoradiographic study, Neurosci. Abstr., 3 (1977) 56
403 13 Kerr, F. W. L., Facial, vagal and glossopharyn~al nerves in the cat. Afferent connections, Arch. Neurol. (Chic.)., 6 (1962) 264-281. 14 Norgren, R., Ascending central gustatory pathways, J. comp. Neurol., 150 (1973) 217-238. 15 Rogers, R. C., Novin, D. and Butcher, L. L., Putative hepatic sodium receptors activate neurons in the ventral basal thalamus, Neurosci. Abstr., 4 (1978) 519. 16 Ruscak, M. and Ruscakova, P., Metabolism of neural tissue in relation to ion movements in vitro and in situ. In Regulation of Brain Metabolism in vitro in Relation to Changes of Ionic Equilibrium, University Park Press, Baltimore, 1971, p. 37-48. 17 Scheibel, M. E. and Scheibei, A. B., The organization of the nucleus reticularis thalami. A Golgi study, Brain Research, 1 (1966) 43-62. 18 Schmitt, M., Influences of hepatic portal receptors on hypothalamic feeding and satiety centers, Am. J. Physiol., 225 (1973) 1089-1095. 19 Torvik, A., The ascending fibers from the main trigeminal sensory nucleus. An experimental study in the cat, Amer. J. Anat., 100 (1957) 1-16.
Brain Research, 168 (1979) 398-403 © Elsevier/North-Holland BiomedicalPress
Hepatic sodium and osmoreceptors activate neurons in the ventrobasal thalamus
RICHARD C. ROGERS, DONALD NOVIN and LARRY L. BUTCHER Brain Research Institute and Department of Psychology, University of California, Los Angeles, Calif. 90024 (U.S.A.)
(Accepted January 25th, 1979)
Electrophysiological studies of multifiber preparations of the hepatic branch of the vagus nerve in rats and rabbits have indicated the presence of hepatic sodium receptors and osmoreceptors 1,8. These hepatovagal signals have a significant effect on physiological mechanisms concerned with osmoregulation. In rats, changes in urine volume follow changes in hepatic osmolarity more closely than changes in systemic osmolarity. That is, simultaneous infusions of hypertonic saline into the vena cava and water into the hepatic portal vein produced a prompt and copious diuresis whereas a reversal of the infusion pattern produced antidiuresislL Resection of the hepatic branch of the vagus eliminated this hepatically mediated effect8. The hepatic receptor inputs affect behavioral osmoregulation also, since hepaticportal infusions of inhibitors of the electrogenic sodium-potassium pump (sodium chloride, Ouabain) shift the normally strong saline taste preference of the rat toward rejection. Venous infusions of the same agents were without effect. Right cervical vagotomy eliminates this hepatically mediated preference shift 4. The central neural structures that relay these hepatovagal signals were not known with any certainty until recently, but anatomical 2,~s,14,1a, and neurophysiologica15,~5,18 studies point to a pathway closely paralleling the central gustatory system. Anatomical and indirect neurophysiological evidence supports the notion that vagal afferents terminate in the nucleus of the solitary tract (NTS). NTS neurons then project to the pontine parabrachial nucleus whose axons bifurcate, one branch projecting dorsally to the somatosensory segment of the ventral thalamus and the other projecting to the hypothalamus and amygdala. Although cells scattered throughout the diencephalon respond to portal infusions of saline and glucose is, no firm conclusions have been made regarding the afferent projections to those cells. However, the studies reported here provide perhaps the first physiological and anatomical verification of hepatovagal afferent flow through the dorsal part of the gustatory pathway. Rats anesthetized with urethane (1.5 g/kg) were provided with both inferior vena cava and hepatic portal cannulae. After mounting the rat in the stereotaxic frame the
399
I !
,
[ ~l
'!;,
rJ
hwhw
i! hw
hm
hs
vs hs
-
["
I
'q
hw hw h w v w h w
!t hg
hu
B
vw hk
hm
hs
hc
Fig. 1. Typical responses of hepatically activated VPM units. A: record of firing rate vs time and infusion condition. VPM neuron activated by hepatic water infusions, inhibited generally by hepatic hyperosmotic solutions. Note inhibition of water activation by preceding infusion of hypertonic sodium chloride. Abbreviations: vw, vena cava water; hw, hepatic water; hs, hepatic 0.3 M sodium chloride; hm, hepatic 0.6 M mannose; hg, hepatic 0.6 M glucose; and hu, hepatic 0.6 M sucrose. Infusion vol. 0.15 ml in all cases. B: VPM unit was activated only by hepatic infusions of sodium chloride and choline chloride. Infusion vol. was 0.15 ml for all cases. Abbreviations: hs, hepatic 0.3 M sodium chloride; vs, vena cava 0.3 M sodium chloride; vw, vena cava water; hk hepatic 0.3 M potassium chloride; hm, hepatic 0.6 M mannose; and hc, hepatic 0.3 M choline chloride. Calibration bars, 30 spikes/see, 5 min. cannulae were attached to syringes containing either pure water or 0.3 M sodium chloride. Double-barreled glass microelectrodes with a tip diameter o f between 1 and 5 # m filled with 0.2 Tris buffer (pH 8.6) and 5 % horseradish peroxidase (HRP, Sigma type VI) and a 4 % Pontamine, 5 % potassium chloride solution were lowered through a trephination to recording sites in the brain via hydraulic microdrivea. Recording t h r o u g h the Pontamine electrode, single-unit records were displayed oscillographically, and firing rate was constantly monitored with a Schmitt-trigger and pulse integrator-polygraph apparatus. After isolating a suitable neuron, small a m o u n t s (0.1-0.2 ml) o f hypertonic saline were infused into the hepatic portal while at the same time, water was infused into the vena cava. This simultaneous infusion paradigm
400
Fig. 2. Typical results of a small H R P injection into the VPM. A: large arrow indicates a typical small injection into hepatically activated site in the dorsal VPM. Small arrow indicates 'unsuccessful' electrode track. Abbreviations; mmt, mammilothalamic tract; ml, medial lemniscus; ic, internal capsule; and v, third ventricle. Calibration bar, 500/~m. B: large arrow indicates HRP-labeled cell in the parabrachial nucleus resulting from the injection in A above. Small arrows indicate thionin-counterstained cells out of the plane of focus, Calibration bar, 15/~m.
401 prevented salt or water accumulation during the initial stages of the experiment as mixing of the two solutions in the proximal vena cava produced isotonic saline. The infusions were repeated in reverse order (ie. the vena cava received saline and the portal vein, water) when the cell's firing rate, post-infusion, returned to the preinfusion baseline. If a replicable and significant change in firing rate was observed following the infusions, 0.3 M sodium chloride or water solutions were applied to the portal or caval veins alone in order to determine which route produced the effect. If portal infusions alone affected the cell under examination, then a variety of solutions were portally infused to determine whether that cell responded to hepatic sodium alone or to hepatic osmotic stimulation. Mannitol, glucose and sucrose, all at a concentration of 0.6 M, were infused as a test for osmotically sensitive receptors while choline chloride and potassium chloride were used as non-sodium ionic stimuli. Following these procedures, very small amounts of HRP were electrophoretically applied to the recording site (2.5/~A positive DC applied for 2 rain producing an injection site less than 300/zm in diameter, including halo; current was applied longer to achieve larger injection sites). The positions of numerous non-hepatically driven neurons were likewise marked with Pontamine using negative DC. Twenty-four hours after HRP application the rats were perfused with a 0.1 M monobasic phosphate buffer solution (pH 7.4) followed by a solution of 1 ~ paraformaldehyde-3 ~ glutaraldehyde in phosphate buffer. The brains were removed, cut on a freezing microtome and treated for the demonstration of retrograde transport of HRP according to the method of De Olmos 7. Numerous ceils in or near the ventro-postero-medial nucleus of the thalamus (VPM) responded to hepatic portal infusions. The responses were of two general types. The first (Fig. 1A) type of neuronal unit responded only to hepatic infusions of sodium or choline chloride. Potassium chloride and non-ionic, hyperosmotic solutions were without effect. The second type of thalamic cell (Fig. 1B) responded to changes in portal osmolarity; ie. in this case the cell was inhibited by both ionic and non-ionic hyperosmotic solutions infused into the portal vein, but was activated by the presence of water in the hepatic portal. Anatomical segregation of the responses was not seen; both types of cells appeared evenly distributed throughout the VPM. Very small injections of HRP through the recording electrodes were often insufficient to demonstrate retrograde transport. However, in those cases where transport from hepatically activated areas was observed, cells in the parabrachial nuclei were always demonstrated (Fig. 2A, B). With larger injections cells in the principal trigeminal sensory nucleus, nucleus reticularis thalami, substantia nigra (pars reticulata), the nucleus gracilis and the dentate nucleus of the cerebellum were demonstrated. Projections from the principal trigeminal sensory nucleus, nucleus reticularis thalami and the substantia nigra are probably directed toward the VPM 8,17,t9 while demonstrations of projections from the nucleus gracilis and the dentate nucleus may have been the result of spread of HRP into the adjacent ventro-postero-lateral nucleus of the thalamusl0AL From these results it is apparent that osmoreceptors and sodium receptors in the liver activate neurons in the ventral sensory thalamus. Blake and Lin4 proposed that
402 activity o f the hepatic sodium receptor depends on the electrogenic sodium-potassium pump. The finding o f cells in the sensory thalamus that responded only to the presence of hepatic sodium and choline support their hypothesis as both ions inhibit the sodium-potassium p u m p 16. This inhibition would presumably depolarize nerve fibers in the liver thereby increasing their excitability 4. Portal infusions of potassium chloride had n o effect on V P M cells in our studies. This m a y be due to the activation of the electrogenic p u m p by the presence of potassium, which would cause receptor elements to hyperpolarize, reducing excitability 4. The demonstration o f another class of response, the hepatic osmoreceptor response, indicates that perhaps both a specific sodium receptor and an osmoreceptor m a y exist in the liver and that they share c o m m o n afferent projections. This finding o f two classes of hepatically activated thalamic neurons m a y help resolve some of the controversy with respect to the presence or absence of hepatic sodium receptors a,4 or osmoreceptors 1,11. H R P histochemistry supports the presumption that hepatovagal afferent pathways in the brain are, at least in part, parallel to a previously described gustatory afferent system that includes the nucleus of the solitary tract, the parabrachial nucleus and the ventrobasal thalamus. This work was supported by N I N C D S G r a n t NS 7687 to D. N. and U S P H S G r a n t NS 10928 to L.L.B. ; R.C.R. was supported by N I M H Pre-doctoral Fellowship M H06415. We thank K e n Hirabayashi for assistance with the H R P method and Gerlinda Rogers and K o n r a d Talbot for their assistance in the interpretation o f the material. 1 Adachi, A., Niijima, A. and Jacobs, H. L., A hepatic osmoreceptor mechanism in the rat: electrophysiological and behavioral studies, Amer. J. Physiol., 213 (1976) 1043-1049. 2 Allen, W. F., Origin and distribution of the tractus solitarius in the guinea pig, J. cornp. Neurol., 35 (1923) 171-204. 3 Andrews, W. H. H. and Ohrbach, J., Sodium receptors activating some nerves of perfused rabbit livers, Amer. J. Physiol., 227 (1974) 1273-1275. 4 Blake, W. D. and Lin, K. K., Effects of hepatic portal vein infusion of glucose and sodium solutions on the control of saline drinking in the rat, J. Physiol. (Lond.), 274 (1978) 129-139. 5 Dell, P. and Olson, R., Projections thalamiques, corticales et c6r6belleuses des afferences visc6rales vagales, C. R. Soc. Biol. (Paris), 145 (1951) 1084-1087. 6 Dennhardt, R., Ohm, W. W. and Haberich, F. J., Die Ausschaltung der Lebediste des N. vagus an der wachen Ratte und ihr einfluss auf hepatogene Diurese - - indirekter Bewis ffir die afferente Leitung der Leber-Osmoreceptoren fiber den N. Vagus, Pfliigers Arch. ges. PhysioL, 328 (1971) 51-56. 7 De Olmos, J. S., An improved HRP method for the study of central nervous connections, Exp. Brain Res., 29 (1978) 541-551. 8 Faull, R. L. M. and Carman, J. B., Ascending projections of the substantia nigra in the rat, J. comp. NeuroL, 132 (1968) 73-93. 9 Graybiel, A. M. and Devor, M., A microelectrode delivery technique for use with horseradish peroxidase, Brain Research, 68 (1974) 167-173. 10 Groenwegen, H. J., Boesten, A. J. P. and Voogd, J., The dorsal column nuclear projections to the nucleus ventralis posterior lateralis in the cat: an autoradiographic study, J. comp. Neurol., 162 (1975) 505-518. 11 Haberich, F. J., Osmoreception in the portal circulation, Fed. Proc., 27 (1968) 1137-1141. 12 Kalil, K., Topographic organization of projections from the dentate and interpositus nuclei in the rhesus monkey: an autoradiographic study, Neurosci. Abstr., 3 (1977) 56
403 13 Kerr, F. W. L., Facial, vagal and glossopharyn~al nerves in the cat. Afferent connections, Arch. Neurol. (Chic.)., 6 (1962) 264-281. 14 Norgren, R., Ascending central gustatory pathways, J. comp. Neurol., 150 (1973) 217-238. 15 Rogers, R. C., Novin, D. and Butcher, L. L., Putative hepatic sodium receptors activate neurons in the ventral basal thalamus, Neurosci. Abstr., 4 (1978) 519. 16 Ruscak, M. and Ruscakova, P., Metabolism of neural tissue in relation to ion movements in vitro and in situ. In Regulation of Brain Metabolism in vitro in Relation to Changes of Ionic Equilibrium, University Park Press, Baltimore, 1971, p. 37-48. 17 Scheibel, M. E. and Scheibei, A. B., The organization of the nucleus reticularis thalami. A Golgi study, Brain Research, 1 (1966) 43-62. 18 Schmitt, M., Influences of hepatic portal receptors on hypothalamic feeding and satiety centers, Am. J. Physiol., 225 (1973) 1089-1095. 19 Torvik, A., The ascending fibers from the main trigeminal sensory nucleus. An experimental study in the cat, Amer. J. Anat., 100 (1957) 1-16.