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Physiological responses to midbrain thermal stimulation in the cat
542
Brain Research, 128 (1977) 542 546 ~) Elsevier/North-Holland Biomedical Press
Physiological responses to midbrain thermal stimulation in the cat
MICHAEL JOHN CRONIN* and MARY ANN BAKER** Dep~rtment of Physiology, U.S.C. Medical Center, Los Angeles, Calif 90033 (U.S.A.)
(Accepted October 14th, 1976)
Discrete thermal stimulation of several regions of the mammalian brain stem induces physiological and behavioral adjustments directed toward reestablishing normal brain temperature6,7,13,19, 23. The responses to locally induced temperatures are presumably initiated by temperature sensitive neurons which have been demmonstrated in these regions. The preoptic-anterior hypothalamic area provides the best examples of dramatic changes in heat loss with thermal stimulation 6 coincident with a high density ofthermoresponsive neurons 15. Heating and cooling of the medulla modifies not only physiological and behavioral thermoregulation 19,23 but also the firing of single neurons in the same region 18. In a companion papeO 2, we report a high concentration of thermosensitive neurons in the caudal paramedian midbrain of anesthetized cats. The experiments reported here were designed to determine whether local thermal stimulation of this part of the midbrain would elicit thermoregulatory responses. We studied 10 acute and 3 chronic cats. In the acute experiments, the animals were anesthetized with chloral hydrate and a water-perfused thermode was placed in the caudal midbrain at stereotaxic AP 012. Temperatures of the thermodes and tlle anterior hypothalamus were recorded with thermocouples. A thermocouple was also placed in the nasal cavity to record respirations and vasomotor changes on the nasal mucosa 3,'5 and, in 5 animals, femoral arterial blood pressure was recorded. In the chronic experiments, cats were initially anesthetized with Nembutal and thermocouples were chronically implanted in the anterior hypothalamus and the nasal cavity. A bilateral water-perfused thermode (WPT) was implanted in one animal and bilateral radiofrequency thermodes (RFT) were implanted in two animals~°, 22. The thermodes were separated by 4 mm and straddled the midline at AP 0, stimulating the region lich in thermosensitive neurons 11,1~. Positions of all implanted devices were verified histologically in both acute and chronic experiments. * Present address: School of Medicine, Department of Obstetrics and Gynecology, University of California at San Francisco, San Francisco, Calif. 94143, U.S.A. ** To whom requests for reprints should be addressed. Present address: Program in Biomedical Sciences and Department of Biology, University of California at Riverside, Riverside, Calif. 92502, U.S.A.
543 Chronic animals were allowed two weeks to recover from surgery and were habituated to the recording situation before experiments began. During the runs, the cats were unrestrained in a large cage within a temperature-controlled, sound-attenuated recording chamber at 21 ± 1 °C. Once the chamber door was closed, midbrain thermal stimulation was not begun until the animal's temperature had stabilized. Thermode temperature changes of 0.5-5 °C, lasting at least 3 min and not more than 10 min, were used. In the R F T experiments, to lessen the possibility that the cats would predict the temporal cycle of heating, the durations of heat-on and heat -off were chosen randomly between 3 and 10 min. The WPT required 1-4 min to reach the desired temperature once the perfusion was begun, in part because of the residual water remaining in the tubing from the last event, and at least 1 min to return to baseline temperature once the perfusion was stopped (Fig. 1). It was a particular problem to keep the WPT working in the unrestrained cat, which accounts for the smaller mean duration of cooling (Table I). The R F T required 30 sec to heat and approximately 1 min to return to baseline. Temperatures of the thermodes, the hypothalamus and the nasal mucosa were recorded continuously on a Grass Model 7 polygraph. I n the anesthetized cats, we observed changes in respiratory rate and nasal mucosal temperature during heating (1-5 °C) and cooling (1-5 °C) of the midbrain. In interpreting these changes, it was necessary to rule out hypothalamic thermal stimulation as the initiating event, since midbrain thermal stimulation, especially if prolonged, often induced changes in hypothalamic temperature in the same direction as the midbrain temperature change. In 71 of 105 heating or cooling events, the respiratory rate increased with midbrain heating and decreased with midbrain cooling. In 121 of 175 periods of midbrain thermal stimulation, the nasal mucosal temperature rose during midbrain heating and fell during midbrain cooling. These responses are significant, even though they were observed in anesthetized animals, since respiratory rate and nasal mucosal vasomotor tone are two of the most important mechanisms regulating peripheral heat loss in the cat 3. In the 5 experiments in which arterial blood pressure was recorded in anesthetized cats, changes in blood pressure occurred during 77 of 98 periods of thermal stimulation of the midbrain. Thirty-eight heating events always decreased mean arterial blood pressure and 39 cooling events always increased it, with no obvious change in pulse pressure. Neither the amount of pressure change, which did not exceed 20 mm Hg, nor the 21 displacements that produced no obvious pressure changes (2 cats) were related to the degree, direction or duration of the temperature change. Arterial blood pressure changes, while not thermoregulatory responses, usually accompany thermoregulatory vasomotor activityS,14,2~. The primary variable observed in the chronic experiments was the temperature of the anterior hypothalamus, a sensitive indicator of changes in peripheral heat loss in the cat s. We measured the rate of change of hypothalamic temperature (ATH/min) during midbrain thermal stimulation, calculating the change in hypothalamic temperature each minute after the thermode had reached a steady temperature and during post-heating and post-cooling periods. The average rates of hypothalamic temperature change during all thermal stimulations of the midbrain and all post-stimulation periods
544
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_
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WPT
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Thypot a, . . . . ',
Tthe~n~e I
. . . .
0
~
i
5
. . . .
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-
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r 38,4 38.1 r"42.1 1-38.1
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15
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20
MINUTES Fig. 1. Hypothalamic temperature changes correlated with both water-perfused thermode (WPT) and radiofrequency thermode (RFT) induced midbrain heating in unanesthetized cats. It is suggested that changes in midbrain temperature produced by the thermode elicit changes in nasal heat loss which cause shifts in hypothalamic temperature. Initial cooling of the WPT is due to the residual water remaining in the tubing from the last event.
were pooled and a mean rate calculated in each condition (i.e., heating, cooling or postheating, post-cooling). The pooled mean rates of hypothalamic temperature change during periods of midbrain thermal stimulation and during the post-stimulation periods were compared statistically to a theoretical population mean rate of 0.000 °C/ min with a 1-sample, 2-tailed t-test. To verify the assumption that the rate of change of hypothalamic temperature was zero when no midbrain thermal stimulation was present, the mean A T n / m i n was calculated in each animal in sham runs at the same time of day as the experimental runs. The durations of the periods used for analysis were randomly determined between 3 and l0 min and the pooled mean A T I d m i n was calculated in the same way as in the experimental runs (Table I). When no thermal stimulation of the midbrain was present, the ATH/min was not significantly different from the theoretical 0.000 °C/min (P < 0.8). In the unanesthetized, unrestrained cats with WPT's and RFT's, we found significant hypothalamic cooling with midbrain heating (Table I, Fig. l). With midbrain heating by the WPT's, the hypothalamic temperature decreased at a mean rate of--0.03 °C/min while midbrain cooling with the W P T ' s induced a rise in hypothalamic temperature at a rate of +0.02 °C/rain. In the two cats with RFT's, data quantitatively similar to that of the WPT heating was obtained (Table I). Since the degree of heating could be easily controlled with the RFT's, we tested thermode heating steps of 0.5 °C and 1.0 °C. The rate of hypothalamic cooling with 1.0 °C midbrain heating was almost twice that present with 0.5 °C midbrain heating, and both were significantly different from no change (Table l). In addition, in both the WPT and the R F T preparations, the post-heating rate of hypothalamic temperature change neither rebounds toward the origin al temperature nor continues downward, still influenced by the heating episode. Hypothalamic temperatures recorded on placing the cats into the recording chamber
545 TABLE 1 Hypothalamic temperature change with midbrain thermostimulation* Thermode Number Stimulation 7"thermode n** o f cats condition (°C) ± S.E.M.
WPT
1 1
RFT
1 2 2 2
Stim. +2.2 q- 0.1 36 Post-st±re. 0.0 36 Stim. --2.2 -I- 0.1 36 Post-stim. 0.0 36 Sham 0.0 35 Stim. +0.5 ± 0.0 38 Post-st±re. 0.0 38 Stim. + 1.0 ± 0.0 40 Post-stim. 0.0 40 Sham 0.0 50
Time (rain)
AT hypothal./ min ± S.E.M.
P
S-NS***
5.0 4.8 3.9 4.2 6.6 6.1 5.7 5.7 6.2 6.2
-4).034 ± 0.006 + 0 . 0 0 1± 0.004 +0.020 ± 0.008 -4).017 ± 0.003 0.000 :k 0.004 -4).015 ± 0.005 -4).008 ± 0.004 ---0.026± 0.006 +0.004 ± 0.005 +0.002 ± 0.005
<0.001 <0.08 <0.02 <0.001 <0.80 <0.01 <0.10 <0.001 <0.40 <0.6
S NS S S NS S NS S NS NS
* Freely behaving cats in 21 °C ambient temperature. ** n, number of periods of thermal stimulation; each cat in 2-cat determinations contributed exactly 1/2 of the 'n' value. *** S, significant difference from 0.00 °C/min; NS, no significant difference from 0.000 °C/rain. were in the normal range (38.5-39.5 °C) as was the spontaneous range of brain temperatures recorded when these cats were not thermally stimulated. Data is presented from both anesthetized and freely behaving cats, suggesting that the caudal midbrain possesses the capacity to sense its temperature and implement normalizing responses. Particularly small thermode temperature steps in the midbrain (0.5 °C) can force the brain to lower its temperature (Table I) at a small but significant rate (average o f - - 0 . 2 °C/10 min). The subtlety of the response may be due to an inherent limitation of the midbrain's power to change brain temperature under the conditions of this experiment or because this area is differentially activated at various ambient temperatures so that its potential is masked at thermoneural ambient temperatures. A discussion of this second hypothesis is presented elsewhere 1°. In studies in both anesthetized and unanesthetized rabbits, thermal stimulation of the rostral midbrain consistently modified oxygen consumption 13, shivering threshold 7 and the EEG pattern 2o. Midbrain transection studies 9 and the actions of both pyrogen 24,27 and anesthetics 2 in the midbrain also suggest its direct participation in temperature regulation. Contrary evidence has been presented in the behaving monkey in which unilateral temperature changes of the rostral midbrain did not elicit changes in the rectal or mean skin temperature, the air temperature selected or the metabolic rate 1. Finally, probing of the midbrain in search of thermosensitive single neurons to justify the above responses has yielded few units in the rostral sector of the midbrain 7,1z, 16,20,21, while a high density of neurons sensitive to brain stem11,12, whole body z6 and cutaneous 17 heating has been discovered in the caudal paramedial mesencephalon. From the results of these studies and the experiments reported here, it appears that the caudal midbrain thermosensors are independently capable of adjusting brain temperature and may contribute substantially to homeothermy in the cat.
546 We sincerely thank Valerie Elliott for typing the manuscript. This work was supported by National Science Foundation Grant BMS 74-14665.
I Adair, E. R. and Stitt, J. T., Behavioral temperature regulation in the squirrel monkey: effects of midbrain temperature displacements, J. Physiol. (Paris'), 63 (1971) 191 194. 2 Amini-Sereshki, L., Extrahypothalamic thermoregulation in cats, Anat. Rec., [81 (1975) 301. 3 Baker, M. A., Influence of the carotid rete on brain temperature in cats exposed to hot environments, J. Physiol. (Lond.), 220 (1972) 711 728. 4 Baker, M. A., Burrell, E., Penkus, J. and Hayward, J. N., Capping and stabilizing chronic intravascular cannulae, J. appl. Physiol., 24 (1968) 577 579. 5 Baker, M. A., Cronin, M. J. and Mountjoy, D. G., Variability of skin temperature in the waking monkey, Amer. J. PhysioL, 230 (1976) 449 455. 6 Bligh, J., The thermosensitivity of the hypothalamus and thermoregulation in mammals, Biol. Rev., 41 (1966) 317-367. 7 Cabanac, M. et Hardy, J. D., Responses unitaires et thermordgulatrices Iors de rochauffements et refroidissements loca[isds de la r6gion pr6optique et du mdsenc6phale chez [e lapin, J. Physiol. (Paris), 61 (1969) 331 347. 8 Chai, C. Y. and Lin, M. T., Effects of heating and cooling the spinal cord and medulla oblongata on thermoregulation in monkeys, J. Physiol. (Loml.), 225 (1972) 297 308. 9 Chambers, W. W., Seigel, M. S., Liu, J. C. and Liu, C. N., Thermoregulatory responses of decerebrate and spinal cats, Exp. Neurol., 42 (1974) 282-299. 10 Cronin, M. J., Midbrain ThermosensitiviO, with Special Re[erence to the Serotonht System~ P h . D . Thesis, University of Southern California, 1976. I 1 Cronin, M. J. and Baker, M. A., Heat-sensitive midbrain raphe neurons in the anesthetized cat, Brahl Research, 110 (1976) 175-181. 12 Cronin, M. J. and Baker, M. A., Thermosensitive neurons in the midbrain of the cat, Brain Research, 128 (1977) 461-472. 13 Hardy, J. D., Thermoregulatory responses to temperature changes in the midbrain of the rabbit, Fed. Proc., 28 (1969) 713. 14 Hayward, J. N. and Baker, M. A., Diuretic and thermoregulatory responses to preoptic cooling in the monkey, Amer. J. Physial., 214 (1968) 843-850. 15 Hensel, H., Neural processes in thermoregulation, Physiol. Rev., 53 (1973) 948 1017. 16 Hori, T. and Nakayama, T., Effects of biogenic amines on central thermoresponsive neurones in the rabbit, J. Physial. (Lond.), 232 (1973) 71 85. 17 Jahns, R., Different proiections of cutaneous thermal inputs to single units of the midbrain raphe nuclei, Braht Research, 101 (1976) 355 361. 18 Lee, H. K. and Chai, C. Y., Temperature-sensitive neurons in the medulla oblongata of the cat, Brain Research, 104 (1976) 163-165. 19 Lipton, J. M., Thermosensitivity of medula ob[ongata in control of body temperature, Amer. J. Physiol., 224 (1973) 890-897. 20 Nakayama, T. and Hardy, J. D., Unit responses in the rabbit's brain stem to changes in brain and cutaneous temperature, J. appl. Physiol., 27 (1969) 848 857. 21 Nakayama, T. and Hori, T., Effects of anesthetic and pyrogen on thermally sensitive neurons in the brainstem, J. appl. Physiol., 34 (1973) 351 355. 22 Parmeggiani, P. L., Franzini, C., Lenzi, P. and Zamboni, G., Threshold of respiratory responses to preoptic heating during sleep in freely moving cats, Brain Research, 52 (1973) 189-201. 23 Roberts, W. W., and Mooney, R. D., Brain areas controlling thermoregulatory grooming, prone extension, lecomotion and tail vasodilatation in rats, J. comp. Physiol. Psychol., 86 (1974) 470 480. 24 Rosendorff, C. and Mooney, J. J., Central nervous system sites of action of a purified leucocyte pyrogen, Amer. J. Physiol., 220 (1971) 597 603. 25 Tabatabai, M., Respiratory and cardiovascular responses resulting from heating the medulla oblongata in cats, Amer. J. Physiol., 222 (1972) 1558 1564. 26 Weiss, B. L. and Aghajanian, G. K., Activation of brain serotonin metabolism by heat: role of midbrain raphe neurons, Brain Research, 26 (I 971 ) 37 48. 27 Wit, A. and Wang, S. C., Temperature-sensitive neurons in preoptic/anterior hypothalamic region : effects of increasing ambient temperature, Amer. J. Physiol., 215 (I 968) 1151-1159.
Brain Research, 128 (1977) 542 546 ~) Elsevier/North-Holland Biomedical Press
Physiological responses to midbrain thermal stimulation in the cat
MICHAEL JOHN CRONIN* and MARY ANN BAKER** Dep~rtment of Physiology, U.S.C. Medical Center, Los Angeles, Calif 90033 (U.S.A.)
(Accepted October 14th, 1976)
Discrete thermal stimulation of several regions of the mammalian brain stem induces physiological and behavioral adjustments directed toward reestablishing normal brain temperature6,7,13,19, 23. The responses to locally induced temperatures are presumably initiated by temperature sensitive neurons which have been demmonstrated in these regions. The preoptic-anterior hypothalamic area provides the best examples of dramatic changes in heat loss with thermal stimulation 6 coincident with a high density ofthermoresponsive neurons 15. Heating and cooling of the medulla modifies not only physiological and behavioral thermoregulation 19,23 but also the firing of single neurons in the same region 18. In a companion papeO 2, we report a high concentration of thermosensitive neurons in the caudal paramedian midbrain of anesthetized cats. The experiments reported here were designed to determine whether local thermal stimulation of this part of the midbrain would elicit thermoregulatory responses. We studied 10 acute and 3 chronic cats. In the acute experiments, the animals were anesthetized with chloral hydrate and a water-perfused thermode was placed in the caudal midbrain at stereotaxic AP 012. Temperatures of the thermodes and tlle anterior hypothalamus were recorded with thermocouples. A thermocouple was also placed in the nasal cavity to record respirations and vasomotor changes on the nasal mucosa 3,'5 and, in 5 animals, femoral arterial blood pressure was recorded. In the chronic experiments, cats were initially anesthetized with Nembutal and thermocouples were chronically implanted in the anterior hypothalamus and the nasal cavity. A bilateral water-perfused thermode (WPT) was implanted in one animal and bilateral radiofrequency thermodes (RFT) were implanted in two animals~°, 22. The thermodes were separated by 4 mm and straddled the midline at AP 0, stimulating the region lich in thermosensitive neurons 11,1~. Positions of all implanted devices were verified histologically in both acute and chronic experiments. * Present address: School of Medicine, Department of Obstetrics and Gynecology, University of California at San Francisco, San Francisco, Calif. 94143, U.S.A. ** To whom requests for reprints should be addressed. Present address: Program in Biomedical Sciences and Department of Biology, University of California at Riverside, Riverside, Calif. 92502, U.S.A.
543 Chronic animals were allowed two weeks to recover from surgery and were habituated to the recording situation before experiments began. During the runs, the cats were unrestrained in a large cage within a temperature-controlled, sound-attenuated recording chamber at 21 ± 1 °C. Once the chamber door was closed, midbrain thermal stimulation was not begun until the animal's temperature had stabilized. Thermode temperature changes of 0.5-5 °C, lasting at least 3 min and not more than 10 min, were used. In the R F T experiments, to lessen the possibility that the cats would predict the temporal cycle of heating, the durations of heat-on and heat -off were chosen randomly between 3 and 10 min. The WPT required 1-4 min to reach the desired temperature once the perfusion was begun, in part because of the residual water remaining in the tubing from the last event, and at least 1 min to return to baseline temperature once the perfusion was stopped (Fig. 1). It was a particular problem to keep the WPT working in the unrestrained cat, which accounts for the smaller mean duration of cooling (Table I). The R F T required 30 sec to heat and approximately 1 min to return to baseline. Temperatures of the thermodes, the hypothalamus and the nasal mucosa were recorded continuously on a Grass Model 7 polygraph. I n the anesthetized cats, we observed changes in respiratory rate and nasal mucosal temperature during heating (1-5 °C) and cooling (1-5 °C) of the midbrain. In interpreting these changes, it was necessary to rule out hypothalamic thermal stimulation as the initiating event, since midbrain thermal stimulation, especially if prolonged, often induced changes in hypothalamic temperature in the same direction as the midbrain temperature change. In 71 of 105 heating or cooling events, the respiratory rate increased with midbrain heating and decreased with midbrain cooling. In 121 of 175 periods of midbrain thermal stimulation, the nasal mucosal temperature rose during midbrain heating and fell during midbrain cooling. These responses are significant, even though they were observed in anesthetized animals, since respiratory rate and nasal mucosal vasomotor tone are two of the most important mechanisms regulating peripheral heat loss in the cat 3. In the 5 experiments in which arterial blood pressure was recorded in anesthetized cats, changes in blood pressure occurred during 77 of 98 periods of thermal stimulation of the midbrain. Thirty-eight heating events always decreased mean arterial blood pressure and 39 cooling events always increased it, with no obvious change in pulse pressure. Neither the amount of pressure change, which did not exceed 20 mm Hg, nor the 21 displacements that produced no obvious pressure changes (2 cats) were related to the degree, direction or duration of the temperature change. Arterial blood pressure changes, while not thermoregulatory responses, usually accompany thermoregulatory vasomotor activityS,14,2~. The primary variable observed in the chronic experiments was the temperature of the anterior hypothalamus, a sensitive indicator of changes in peripheral heat loss in the cat s. We measured the rate of change of hypothalamic temperature (ATH/min) during midbrain thermal stimulation, calculating the change in hypothalamic temperature each minute after the thermode had reached a steady temperature and during post-heating and post-cooling periods. The average rates of hypothalamic temperature change during all thermal stimulations of the midbrain and all post-stimulation periods
544
Zhypothalamus .....
_
40.0
f__
WPT
[42s, °c
lIFT
Thypot a, . . . . ',
Tthe~n~e I
. . . .
0
~
i
5
. . . .
..... /~I
I0
f-~ ,
-
. . . .
r 38,4 38.1 r"42.1 1-38.1
F--(
~ \ ~ . _ _ l
15
. . . .
I
"
"
20
MINUTES Fig. 1. Hypothalamic temperature changes correlated with both water-perfused thermode (WPT) and radiofrequency thermode (RFT) induced midbrain heating in unanesthetized cats. It is suggested that changes in midbrain temperature produced by the thermode elicit changes in nasal heat loss which cause shifts in hypothalamic temperature. Initial cooling of the WPT is due to the residual water remaining in the tubing from the last event.
were pooled and a mean rate calculated in each condition (i.e., heating, cooling or postheating, post-cooling). The pooled mean rates of hypothalamic temperature change during periods of midbrain thermal stimulation and during the post-stimulation periods were compared statistically to a theoretical population mean rate of 0.000 °C/ min with a 1-sample, 2-tailed t-test. To verify the assumption that the rate of change of hypothalamic temperature was zero when no midbrain thermal stimulation was present, the mean A T n / m i n was calculated in each animal in sham runs at the same time of day as the experimental runs. The durations of the periods used for analysis were randomly determined between 3 and l0 min and the pooled mean A T I d m i n was calculated in the same way as in the experimental runs (Table I). When no thermal stimulation of the midbrain was present, the ATH/min was not significantly different from the theoretical 0.000 °C/min (P < 0.8). In the unanesthetized, unrestrained cats with WPT's and RFT's, we found significant hypothalamic cooling with midbrain heating (Table I, Fig. l). With midbrain heating by the WPT's, the hypothalamic temperature decreased at a mean rate of--0.03 °C/min while midbrain cooling with the W P T ' s induced a rise in hypothalamic temperature at a rate of +0.02 °C/rain. In the two cats with RFT's, data quantitatively similar to that of the WPT heating was obtained (Table I). Since the degree of heating could be easily controlled with the RFT's, we tested thermode heating steps of 0.5 °C and 1.0 °C. The rate of hypothalamic cooling with 1.0 °C midbrain heating was almost twice that present with 0.5 °C midbrain heating, and both were significantly different from no change (Table l). In addition, in both the WPT and the R F T preparations, the post-heating rate of hypothalamic temperature change neither rebounds toward the origin al temperature nor continues downward, still influenced by the heating episode. Hypothalamic temperatures recorded on placing the cats into the recording chamber
545 TABLE 1 Hypothalamic temperature change with midbrain thermostimulation* Thermode Number Stimulation 7"thermode n** o f cats condition (°C) ± S.E.M.
WPT
1 1
RFT
1 2 2 2
Stim. +2.2 q- 0.1 36 Post-st±re. 0.0 36 Stim. --2.2 -I- 0.1 36 Post-stim. 0.0 36 Sham 0.0 35 Stim. +0.5 ± 0.0 38 Post-st±re. 0.0 38 Stim. + 1.0 ± 0.0 40 Post-stim. 0.0 40 Sham 0.0 50
Time (rain)
AT hypothal./ min ± S.E.M.
P
S-NS***
5.0 4.8 3.9 4.2 6.6 6.1 5.7 5.7 6.2 6.2
-4).034 ± 0.006 + 0 . 0 0 1± 0.004 +0.020 ± 0.008 -4).017 ± 0.003 0.000 :k 0.004 -4).015 ± 0.005 -4).008 ± 0.004 ---0.026± 0.006 +0.004 ± 0.005 +0.002 ± 0.005
<0.001 <0.08 <0.02 <0.001 <0.80 <0.01 <0.10 <0.001 <0.40 <0.6
S NS S S NS S NS S NS NS
* Freely behaving cats in 21 °C ambient temperature. ** n, number of periods of thermal stimulation; each cat in 2-cat determinations contributed exactly 1/2 of the 'n' value. *** S, significant difference from 0.00 °C/min; NS, no significant difference from 0.000 °C/rain. were in the normal range (38.5-39.5 °C) as was the spontaneous range of brain temperatures recorded when these cats were not thermally stimulated. Data is presented from both anesthetized and freely behaving cats, suggesting that the caudal midbrain possesses the capacity to sense its temperature and implement normalizing responses. Particularly small thermode temperature steps in the midbrain (0.5 °C) can force the brain to lower its temperature (Table I) at a small but significant rate (average o f - - 0 . 2 °C/10 min). The subtlety of the response may be due to an inherent limitation of the midbrain's power to change brain temperature under the conditions of this experiment or because this area is differentially activated at various ambient temperatures so that its potential is masked at thermoneural ambient temperatures. A discussion of this second hypothesis is presented elsewhere 1°. In studies in both anesthetized and unanesthetized rabbits, thermal stimulation of the rostral midbrain consistently modified oxygen consumption 13, shivering threshold 7 and the EEG pattern 2o. Midbrain transection studies 9 and the actions of both pyrogen 24,27 and anesthetics 2 in the midbrain also suggest its direct participation in temperature regulation. Contrary evidence has been presented in the behaving monkey in which unilateral temperature changes of the rostral midbrain did not elicit changes in the rectal or mean skin temperature, the air temperature selected or the metabolic rate 1. Finally, probing of the midbrain in search of thermosensitive single neurons to justify the above responses has yielded few units in the rostral sector of the midbrain 7,1z, 16,20,21, while a high density of neurons sensitive to brain stem11,12, whole body z6 and cutaneous 17 heating has been discovered in the caudal paramedial mesencephalon. From the results of these studies and the experiments reported here, it appears that the caudal midbrain thermosensors are independently capable of adjusting brain temperature and may contribute substantially to homeothermy in the cat.
546 We sincerely thank Valerie Elliott for typing the manuscript. This work was supported by National Science Foundation Grant BMS 74-14665.
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