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Auditory entrainment of primate drinking rhythms following partial suprachiasmatic nuclei lesions
Physiology &Behavior,Vol. 31, pp. 573-576. Pergamon Press Ltd., 1983. Printed in the U.S.A.
BRIEF COMMUNICATION
Auditory Entrainment of Primate Drinking Rhythms Following Partial Suprachiasmatic Nuclei Lesions C H A R L E S A. F U L L E R , * R A L P H L Y D I C , x F R A N K M. S U L Z M A N , 2 H . E L L I O T T A L B E R S , a B E V E R L Y T E P P E R a A N D M A R T I N C. M O O R E - E D E
Department of Physiology and Biophysics, Harvard Medical School, Boston, MA 02115 and Division of Biomedical Sciences, University of California, Riverside, CA 92521" R e c e i v e d 28 M a r c h 1983 FULLER, C. A., R. LYDIC, F. M. SULZMAN, H. E. ALBERS, B. TEPPER AND M. C. MOORE-EDE. Auditory entrainment of primate drinking rhythms following partial suprachiasmatic nuclei lesions. PHYSIOL BEHAV 31(4) 573-576, 1983.--In the absence of other environmental cycles, daily variations in auditory stimuli are normally not capable of entraining the circadian rhythms of drinking behavior in the squirrel monkey (Saimirisciureus). However, the drinking rhythm appears to become entrainable by previously ineffective auditory cues after lesions are placed which destroy only the caudal portion of the hypothalamic suprachiasmatic nuclei. The results suggest specificity of function within the SCN and an increased influence of auditory stimuli in animals with impaired SCN function. Squirrel monkey
Circadian rhythms
Drinking
C I R C A D I A N rhythms in physiological, biochemical and behavioral parameters persist with a period close to, but not exactly, 24 hr, in an environment without time cues. In the squirrel monkey (Saimiri sciureus) the approximately 25 hour free-running rhythms are normally synchronized to a 24-hr period by only two types of environmental time cues: light-dark cycles or cycles of food availability [15]. A wide range of other potential time cues have been examined including cycles of auditory stimuli, temperature, social interaction, and water availability. Each of these was ineffective as a synchronizing agent when they were applied with a 24-hr periodicity to squirrel monkeys maintained with continuous light and food available ad lib [15]. The suprachiasmatic nuclei (SCN) of the hypothalamus play a major regulatory role in the circadian timing system of mammals [6,13]. Moore and Eichler [7] and Stephan and Zucker [ 14] first demonstrated that bilateral SCN destruction disrupted physiological and behavioral circadian rhythms in rodents. Since then many investigators have confirmed that the SCN play an essential role in maintaining circadian timekeeping (cf., [6,13] for review). More recently, we have demonstrated that SCN lesions in the squirrel monkey can
1Present 2Present 3Present 4Present
address: address: address: address:
Suprachiasmatic nucleus
Auditory
Entrainment
disrupt circadian feeding and drinking behaviors although the rhythm in body temperature persists [3]. Thus, in this primate the SCN appear to be only one of at least two major pacemakers in the circadian system [8,9]. In the course of studying SCN-lesioned squirrel monkeys in constant light, animals with robust persisting circadian drinking rhythms, apparently entrained to a 24-hour period, were sometimes observed. Subsequent histology showed that these animals had sustained incomplete destruction of the SCN localized to the caudal portion of the nuclei. In this paper we report that following such lesions, previously ineffective auditory stimuli appear to be capable of entraining the persisting circadian drinking rhythm. METHOD Adult male squirrel monkeys (Saimiri sciureus) weighing 900 to 1200 grams were studied while free-ranging in a continuously illuminated (LL:600 lux) isolation chamber maintained at approximately 27°C with food and water provided ad lib. Four intact animals and two animals with partial SCN lesions were studied in these conditions. The lesions were
Dr. Ralph Lydic, Laboratory of Neurophysiology, Harvard Medical School, 74 Fernwood St., Boston, MA 02115. Dr. Frank M. Sulzman, Dept. Biol. Sci., SUNY Binghamton, Binghamton, NY 13901. Dr. H. Elliott Albers, Worcester Foundation for Exper. Biol., 222 Maple Ave., Shrewsbury, MA 01545. Beverly Tepper, Dept. Nutrition, Tufts University, Medford, MA 02155.
Copyright © 1983 Pergamon Press Ltd.--0031-9384/83/100573-04503.00
-rIME OF DAY (HRS~ ..........................
~
...............
-~ ...............
2a
..................
l~qY LL
113
LL NQ
3a 40
FIG. 1. Drinking rhythm of an intact squirrel monkey in constant light (LL) plotted as a function of time of day. Vertical pen strokes represent drinking behavior. From day 12 to 46, the animal was also exposed to the noise-quiet (NQ) cycle described in the text. This data is redrawn from [14].
generated as previously described [3]. The animals were checked at random times every other day to replenish food and water. Drinking behavior was continuously monitored by recording when the monkey completed a low current electrical circuit by making contact with the drinking spout. Total drinking time was automatically recorded each half hour on an Esterline Angus DE2100 digital data collection system. The output from the system was fed into a PDP 11/03 computer for storage and subsequent analysis. The digitized drinking behavior was plotted in a standard circadian double plot by procedures described previously [15]. A linear and non-linear least squares spectral analysis [3] was used to evaluate the period and strength of rhythms in the drinking data. RESULTS Intact squirrel monkeys housed in LL:600 lux with food ad lib demonstrate a free-running circadian drinking rhythm with an average period of approximately 25 hr (Fig. 1; LL). These rhythms were not entrained either by exposing the animals to auditory contact with other monkeys which were entrained to a 24-hr light-dark cycle, or by providing monkeys with a noise-quiet (NQ) sound cycle of intermittent 100 dB white noise provided for 12 hours each day, and background noise of 70 dB for the other 12 hours (Fig. 1; LL, NQ). Because these circadian drinking rhythms free-run through such NQ cycles with no detectable change in period, it is evident that such auditory cues are not effective synchronizers of the circadian drinking rhythm of intact monkeys. While studying the disruption of circadian rhythms produced by SCN ablations, two monkeys were found to have a robust persisting 24.0 hr drinking rhythm (p<0.01) 1-3 months post lesion. This observation was in contrast to
that seen in animals with total SCN lesions in which the circadian drinking rhythm was disrupted [3] or if transiently present had periods greater than 24.0 hr [1]. The possibility therefore existed that the lesions in these two monkeys had made the animals more sensitive to an environmental cycle that did not normally entrain the circadian system. One potential time cue for these monekys was the ambient NQ cycle of the laboratory since the isolation chambers were not completely sound proofed. To determine whether these NQ cycles were entraining the drinking rhythm, the ambient sound cycles were attenuated by exposing the animals to a continuous white noise (NN) of approximately 100 decibels. The drinking rhythms (Fig. 2; LL, NN) immediately began to free-run with a significant (p<0.01) circadian period (25.0 hr in Fig. 2A and 25.5 hr in Fig. 2B). Subsequent histological examination of the hypothalami from the two monkeys which were influenced by these auditory cues revealed that they had sustained only partial SCN lesions (Fig. 3). The lesion-induced damage in both monkeys involved primarily the posterior portion of the SCN, especially along the midline and the ventral borders of the nuclei. DISCUSSION Partial destruction of the SCN, one of the key pacemakers of the circadian timing system, leaves a persisting circadian drinking rhythm. Squirrel monkeys with such lesions can show increased susceptibility to entrainment by ambient noise cycles. These observations are in contrast t o those from both intact squirrel monkeys and animals with total SCN lesions. Circadian rhythms in intact monkeys are insensitive to synchronization by any environmental variable (including sound) except for light and food [14]. Animals with complete SCN lesions, on the other hand, usually do not show such robust rhythmicity in drinking behavior [3].
PRIMATE RHYTHM AUDITORY ENTRAINMENT T,ME OF DAY I . . s l
A
LL NQ
[JR~'
575 8 LL NQ
T,ME OF DAY C..Sl
F,RT
JZ'-~---------.'-."---.E-'~-~----"" "I
. . . .
i
...
. . . . .
u
. . . .
m . . - .
I0
20
20
30 LL NN
qO
LL NN
ql'l
6O FIG. 2. Drinking rhythms of two squirrel monkeys (A and B) following partial lesions of the SCN. During experimental days I through 32, the monkeys were exposed to constant illumination (LL) and ambient noise-quiet (NQ) cycles. From day 33 to 60, each monkey was provided with a constant background noise (NN).
FIG. 3. Projection drawing from the hypothalamus of a squirrel monkey with partially lesioned suprachiasmatic nuclei (SCN). Sections are 100 p. apart and arranged from rostral (A) to caudal (H). The lesioned area is shown as the hatched area above the optic chiasm (CHO). Also shown are the corpus callosum (CC), supraoptic nuclei (SO), paraventricular nuclei (PAL anterior commissure (AC) and third ventricle (111).
576
i'~. ] l fIR t:t 4:'
and even if it is transiently present [I] there is no evidence of entrainment to a 24 hour period in constant light. Although we have interpreted the data in Fig. 2 as indicating that the drinking rhythm is entrained by noise cues in the absence of white noise masking of ambient sounds, it could alternatively be argued that the presence or absence of noise only induces changes in the free-running period. However, there are four arguments to support our interpretation that entrainment did occur. First, in both animals a consistent phase relationship was observed between the onset of drinking rhythm and the time (08:00-09:00) when the ambient laboratory noise and activity commenced each day. Second, the initial phase from which the drinking rhythm initiated its free-run in L L / N N was t h a t predicted from prior entrainment at the observed phase. Third, the free-running period of partial lesioned monkeys' drinking rhythm after application of white noise was similar to that observed in intact monkeys under that light intensity (as is shown in Fig. 1). Fourth, in our experience, no intact animal exposed to the same conditions of temporal isolation has ever shown signs of entrainment or evidence of period changes as a result of ambient laboratory environment. Few studies have examined the specificity of function within the mammalian SCN. We have noted [4] a number of studies where partial lesions of the SCN produced specific disruptions of circadian rhythms, depending on whether the lesions involved pars preopticus suprachiasmaticus or the retrochiasmatic area. Moreover, a recent observation of persisting inverted rhythms in rats [11] may be relevant. These animals may also be showing a sensitivity to the ambient auditory environment of the laboratory when SCN function is impaired. The new phase of the rhythms would
support this. However, there have been no syslcmatic in vestigations into the possible circadian function of these hy pothalamic areas at the anterior or posterior horder~ ,~f the SCN [8,12]. Anatomical studies [5] of the three-dimensional structure of the squirrel monkey SCN have described differences in nuclear organization along the rostro-caudal axis with particularly dense terminals from the retinohypothatamic tract are at the ventral and lateral borders of the S e N [ 16]. Histochemical studies in rats have revealed restricted Iocalizations of various peptides and neurotransmitters throughout the SCN [2]. Particularly relevant are the recenl anatomical studies by Pickard [10] which demonstrate an afferent input to the SCN arising from the nucleus of the lateral lemniscus, a primary auditory relay nucleus. It is possible, therefore, that the partial SCN lesions in the squirrel monkeys in this study might have modified the influence of this auditory input to the SCN. However, it is not clear how partial SCN lesions might enhance the sensitivity of the circadian drinking rhythm to sound cycle. Whatever the mechanism, these lesions appear to have altered the sen~ sitivity of the circadian timing system to the auditory environment. ACKNOWLEDGEMENfS This research was supported by NIH Grant NS-13921: NSF Grant BNS 79-24412; PHS Grant BRS-RR-05816: AF()SR Grant 78-3560; and by NASA Grant NSG-9054. M. C. Moore-Ede was the recipient of NIH-RCDA NS-00247. R. Lydic was supported in part by NIMH-NRSA MH-14275. We thank Sharon Eagon for technical assistance and Louise Kilham and Nancy Price for preparing the manuscript.
REFERENCES I. Albers, H. E., R. Lydic, P. H. Gander and M. C. Moore-Ede. Gradual decay of circadian drinking organization following lesions of the suprachiasmatic nuclei in primates. Neurosci Lett 27: 119-124, 1981. 2. Card, J. P., N. Brecha, H. J. Karten and R. Y. Moore. Immunocytochemical localization of vasoactive intestinal polypeptide-containing cells and processes in the suprachiasmatic nucleus of the rat: light and electron microscopic analysis. J Neurosci 1: 1289-1303, 1981. 3. Fuller, C. A., R. Lydic, F. M. Sulzman, H. E. Albers, B. Tepper and M. C. Moore-Ede. Circadian rhythm of body temperatures persists after suprachiasmatic lesions in the squirrel monkey. Am .I Physiol 241: R285-R391, 1981. 4. Lydic, R., H. E. Albers, B. Tepper and M. C. Moore-Ede. Three-dimensional structure of the mammalian suprachiasmatic nuclei, J Comp Neurol 204: 225-237, 1982. 5. Lydic, R. and M. C. Moore-Ede. Three-dimensional structure of the suprachiasmatic nuclei in the diurnal squirrel monkey. Neurosci Lett 17: 295-299, 1980. 6. Moore, R. Y. The anatomy of central neural mechanisms regulating endocrine rhythms. In: Endocrine Rhythms, edited by D. Krieger. New York: Raven Press, 1979, pp. 63-87. 7. Moore, R. Y. and V. B. Eichler. Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. Brain Res 42: 201-206, 1972.
8. Moore-Ede, M. C. The circadian timing system in mammals: Two pacemakers preside over many secondary oscillators, Fed Proc, in press, 1983. 9. Moore-Ede, M. C., F. M. Sulzman and C. A. Fuller. The Clocks That Time Us: The Circadian Timhlg Sy,~tem in Mammals. Boston: Harvard University Press, 1982, pp. 1-448.
10. Pickard, G. E. The afferent connections of the suprachiasmatic nucleus of the golden hamster with emphasis on the retinohypothalamic projection. J Comp Neurol 211: 65-83, 1982. 11. Richter, C. P. "'Dark-active" rat transformed into "ligh-active'" rat by destruction of 24-hr clock: Function of 24-hr clock and synchronizers. Proc Natl Acad Sci USA 75: 6276-6280, 1978. 12. Rusak, B. Neural mechanisms of entrainment and generation of mammalian circadian rhythms. Fed Proc 38: 258%2595, 1979. 13. Rusak, B. and I. Zucker. Neural regulation of circadian rhythms. Physiol Rev 59: 445-526, 1979, 14. Stephan, F. K. and I. Zucker. Circadian rhythms in drinking behavior and locomotor activity in rats are eliminated by hypothalamic lesions. Proc Natl Acad Sci 69: 1583-1586, 1972. 15. Sulzman, F. M., C. A. Fuller and M. C. Moore-Ede. Environmental synchronizers of squirrel monkey circadian rhythms. ,f Appl Physiol 43: 795-800, 1977. 16. Tigges, J. and W. K. O'Steen. Termination of retinofugal fibers in squirrel monkey: a re-investigation using autoradiographic methods. Brain Res 79: 48%495, 1974.
BRIEF COMMUNICATION
Auditory Entrainment of Primate Drinking Rhythms Following Partial Suprachiasmatic Nuclei Lesions C H A R L E S A. F U L L E R , * R A L P H L Y D I C , x F R A N K M. S U L Z M A N , 2 H . E L L I O T T A L B E R S , a B E V E R L Y T E P P E R a A N D M A R T I N C. M O O R E - E D E
Department of Physiology and Biophysics, Harvard Medical School, Boston, MA 02115 and Division of Biomedical Sciences, University of California, Riverside, CA 92521" R e c e i v e d 28 M a r c h 1983 FULLER, C. A., R. LYDIC, F. M. SULZMAN, H. E. ALBERS, B. TEPPER AND M. C. MOORE-EDE. Auditory entrainment of primate drinking rhythms following partial suprachiasmatic nuclei lesions. PHYSIOL BEHAV 31(4) 573-576, 1983.--In the absence of other environmental cycles, daily variations in auditory stimuli are normally not capable of entraining the circadian rhythms of drinking behavior in the squirrel monkey (Saimirisciureus). However, the drinking rhythm appears to become entrainable by previously ineffective auditory cues after lesions are placed which destroy only the caudal portion of the hypothalamic suprachiasmatic nuclei. The results suggest specificity of function within the SCN and an increased influence of auditory stimuli in animals with impaired SCN function. Squirrel monkey
Circadian rhythms
Drinking
C I R C A D I A N rhythms in physiological, biochemical and behavioral parameters persist with a period close to, but not exactly, 24 hr, in an environment without time cues. In the squirrel monkey (Saimiri sciureus) the approximately 25 hour free-running rhythms are normally synchronized to a 24-hr period by only two types of environmental time cues: light-dark cycles or cycles of food availability [15]. A wide range of other potential time cues have been examined including cycles of auditory stimuli, temperature, social interaction, and water availability. Each of these was ineffective as a synchronizing agent when they were applied with a 24-hr periodicity to squirrel monkeys maintained with continuous light and food available ad lib [15]. The suprachiasmatic nuclei (SCN) of the hypothalamus play a major regulatory role in the circadian timing system of mammals [6,13]. Moore and Eichler [7] and Stephan and Zucker [ 14] first demonstrated that bilateral SCN destruction disrupted physiological and behavioral circadian rhythms in rodents. Since then many investigators have confirmed that the SCN play an essential role in maintaining circadian timekeeping (cf., [6,13] for review). More recently, we have demonstrated that SCN lesions in the squirrel monkey can
1Present 2Present 3Present 4Present
address: address: address: address:
Suprachiasmatic nucleus
Auditory
Entrainment
disrupt circadian feeding and drinking behaviors although the rhythm in body temperature persists [3]. Thus, in this primate the SCN appear to be only one of at least two major pacemakers in the circadian system [8,9]. In the course of studying SCN-lesioned squirrel monkeys in constant light, animals with robust persisting circadian drinking rhythms, apparently entrained to a 24-hour period, were sometimes observed. Subsequent histology showed that these animals had sustained incomplete destruction of the SCN localized to the caudal portion of the nuclei. In this paper we report that following such lesions, previously ineffective auditory stimuli appear to be capable of entraining the persisting circadian drinking rhythm. METHOD Adult male squirrel monkeys (Saimiri sciureus) weighing 900 to 1200 grams were studied while free-ranging in a continuously illuminated (LL:600 lux) isolation chamber maintained at approximately 27°C with food and water provided ad lib. Four intact animals and two animals with partial SCN lesions were studied in these conditions. The lesions were
Dr. Ralph Lydic, Laboratory of Neurophysiology, Harvard Medical School, 74 Fernwood St., Boston, MA 02115. Dr. Frank M. Sulzman, Dept. Biol. Sci., SUNY Binghamton, Binghamton, NY 13901. Dr. H. Elliott Albers, Worcester Foundation for Exper. Biol., 222 Maple Ave., Shrewsbury, MA 01545. Beverly Tepper, Dept. Nutrition, Tufts University, Medford, MA 02155.
Copyright © 1983 Pergamon Press Ltd.--0031-9384/83/100573-04503.00
-rIME OF DAY (HRS~ ..........................
~
...............
-~ ...............
2a
..................
l~qY LL
113
LL NQ
3a 40
FIG. 1. Drinking rhythm of an intact squirrel monkey in constant light (LL) plotted as a function of time of day. Vertical pen strokes represent drinking behavior. From day 12 to 46, the animal was also exposed to the noise-quiet (NQ) cycle described in the text. This data is redrawn from [14].
generated as previously described [3]. The animals were checked at random times every other day to replenish food and water. Drinking behavior was continuously monitored by recording when the monkey completed a low current electrical circuit by making contact with the drinking spout. Total drinking time was automatically recorded each half hour on an Esterline Angus DE2100 digital data collection system. The output from the system was fed into a PDP 11/03 computer for storage and subsequent analysis. The digitized drinking behavior was plotted in a standard circadian double plot by procedures described previously [15]. A linear and non-linear least squares spectral analysis [3] was used to evaluate the period and strength of rhythms in the drinking data. RESULTS Intact squirrel monkeys housed in LL:600 lux with food ad lib demonstrate a free-running circadian drinking rhythm with an average period of approximately 25 hr (Fig. 1; LL). These rhythms were not entrained either by exposing the animals to auditory contact with other monkeys which were entrained to a 24-hr light-dark cycle, or by providing monkeys with a noise-quiet (NQ) sound cycle of intermittent 100 dB white noise provided for 12 hours each day, and background noise of 70 dB for the other 12 hours (Fig. 1; LL, NQ). Because these circadian drinking rhythms free-run through such NQ cycles with no detectable change in period, it is evident that such auditory cues are not effective synchronizers of the circadian drinking rhythm of intact monkeys. While studying the disruption of circadian rhythms produced by SCN ablations, two monkeys were found to have a robust persisting 24.0 hr drinking rhythm (p<0.01) 1-3 months post lesion. This observation was in contrast to
that seen in animals with total SCN lesions in which the circadian drinking rhythm was disrupted [3] or if transiently present had periods greater than 24.0 hr [1]. The possibility therefore existed that the lesions in these two monkeys had made the animals more sensitive to an environmental cycle that did not normally entrain the circadian system. One potential time cue for these monekys was the ambient NQ cycle of the laboratory since the isolation chambers were not completely sound proofed. To determine whether these NQ cycles were entraining the drinking rhythm, the ambient sound cycles were attenuated by exposing the animals to a continuous white noise (NN) of approximately 100 decibels. The drinking rhythms (Fig. 2; LL, NN) immediately began to free-run with a significant (p<0.01) circadian period (25.0 hr in Fig. 2A and 25.5 hr in Fig. 2B). Subsequent histological examination of the hypothalami from the two monkeys which were influenced by these auditory cues revealed that they had sustained only partial SCN lesions (Fig. 3). The lesion-induced damage in both monkeys involved primarily the posterior portion of the SCN, especially along the midline and the ventral borders of the nuclei. DISCUSSION Partial destruction of the SCN, one of the key pacemakers of the circadian timing system, leaves a persisting circadian drinking rhythm. Squirrel monkeys with such lesions can show increased susceptibility to entrainment by ambient noise cycles. These observations are in contrast t o those from both intact squirrel monkeys and animals with total SCN lesions. Circadian rhythms in intact monkeys are insensitive to synchronization by any environmental variable (including sound) except for light and food [14]. Animals with complete SCN lesions, on the other hand, usually do not show such robust rhythmicity in drinking behavior [3].
PRIMATE RHYTHM AUDITORY ENTRAINMENT T,ME OF DAY I . . s l
A
LL NQ
[JR~'
575 8 LL NQ
T,ME OF DAY C..Sl
F,RT
JZ'-~---------.'-."---.E-'~-~----"" "I
. . . .
i
...
. . . . .
u
. . . .
m . . - .
I0
20
20
30 LL NN
qO
LL NN
ql'l
6O FIG. 2. Drinking rhythms of two squirrel monkeys (A and B) following partial lesions of the SCN. During experimental days I through 32, the monkeys were exposed to constant illumination (LL) and ambient noise-quiet (NQ) cycles. From day 33 to 60, each monkey was provided with a constant background noise (NN).
FIG. 3. Projection drawing from the hypothalamus of a squirrel monkey with partially lesioned suprachiasmatic nuclei (SCN). Sections are 100 p. apart and arranged from rostral (A) to caudal (H). The lesioned area is shown as the hatched area above the optic chiasm (CHO). Also shown are the corpus callosum (CC), supraoptic nuclei (SO), paraventricular nuclei (PAL anterior commissure (AC) and third ventricle (111).
576
i'~. ] l fIR t:t 4:'
and even if it is transiently present [I] there is no evidence of entrainment to a 24 hour period in constant light. Although we have interpreted the data in Fig. 2 as indicating that the drinking rhythm is entrained by noise cues in the absence of white noise masking of ambient sounds, it could alternatively be argued that the presence or absence of noise only induces changes in the free-running period. However, there are four arguments to support our interpretation that entrainment did occur. First, in both animals a consistent phase relationship was observed between the onset of drinking rhythm and the time (08:00-09:00) when the ambient laboratory noise and activity commenced each day. Second, the initial phase from which the drinking rhythm initiated its free-run in L L / N N was t h a t predicted from prior entrainment at the observed phase. Third, the free-running period of partial lesioned monkeys' drinking rhythm after application of white noise was similar to that observed in intact monkeys under that light intensity (as is shown in Fig. 1). Fourth, in our experience, no intact animal exposed to the same conditions of temporal isolation has ever shown signs of entrainment or evidence of period changes as a result of ambient laboratory environment. Few studies have examined the specificity of function within the mammalian SCN. We have noted [4] a number of studies where partial lesions of the SCN produced specific disruptions of circadian rhythms, depending on whether the lesions involved pars preopticus suprachiasmaticus or the retrochiasmatic area. Moreover, a recent observation of persisting inverted rhythms in rats [11] may be relevant. These animals may also be showing a sensitivity to the ambient auditory environment of the laboratory when SCN function is impaired. The new phase of the rhythms would
support this. However, there have been no syslcmatic in vestigations into the possible circadian function of these hy pothalamic areas at the anterior or posterior horder~ ,~f the SCN [8,12]. Anatomical studies [5] of the three-dimensional structure of the squirrel monkey SCN have described differences in nuclear organization along the rostro-caudal axis with particularly dense terminals from the retinohypothatamic tract are at the ventral and lateral borders of the S e N [ 16]. Histochemical studies in rats have revealed restricted Iocalizations of various peptides and neurotransmitters throughout the SCN [2]. Particularly relevant are the recenl anatomical studies by Pickard [10] which demonstrate an afferent input to the SCN arising from the nucleus of the lateral lemniscus, a primary auditory relay nucleus. It is possible, therefore, that the partial SCN lesions in the squirrel monkeys in this study might have modified the influence of this auditory input to the SCN. However, it is not clear how partial SCN lesions might enhance the sensitivity of the circadian drinking rhythm to sound cycle. Whatever the mechanism, these lesions appear to have altered the sen~ sitivity of the circadian timing system to the auditory environment. ACKNOWLEDGEMENfS This research was supported by NIH Grant NS-13921: NSF Grant BNS 79-24412; PHS Grant BRS-RR-05816: AF()SR Grant 78-3560; and by NASA Grant NSG-9054. M. C. Moore-Ede was the recipient of NIH-RCDA NS-00247. R. Lydic was supported in part by NIMH-NRSA MH-14275. We thank Sharon Eagon for technical assistance and Louise Kilham and Nancy Price for preparing the manuscript.
REFERENCES I. Albers, H. E., R. Lydic, P. H. Gander and M. C. Moore-Ede. Gradual decay of circadian drinking organization following lesions of the suprachiasmatic nuclei in primates. Neurosci Lett 27: 119-124, 1981. 2. Card, J. P., N. Brecha, H. J. Karten and R. Y. Moore. Immunocytochemical localization of vasoactive intestinal polypeptide-containing cells and processes in the suprachiasmatic nucleus of the rat: light and electron microscopic analysis. J Neurosci 1: 1289-1303, 1981. 3. Fuller, C. A., R. Lydic, F. M. Sulzman, H. E. Albers, B. Tepper and M. C. Moore-Ede. Circadian rhythm of body temperatures persists after suprachiasmatic lesions in the squirrel monkey. Am .I Physiol 241: R285-R391, 1981. 4. Lydic, R., H. E. Albers, B. Tepper and M. C. Moore-Ede. Three-dimensional structure of the mammalian suprachiasmatic nuclei, J Comp Neurol 204: 225-237, 1982. 5. Lydic, R. and M. C. Moore-Ede. Three-dimensional structure of the suprachiasmatic nuclei in the diurnal squirrel monkey. Neurosci Lett 17: 295-299, 1980. 6. Moore, R. Y. The anatomy of central neural mechanisms regulating endocrine rhythms. In: Endocrine Rhythms, edited by D. Krieger. New York: Raven Press, 1979, pp. 63-87. 7. Moore, R. Y. and V. B. Eichler. Loss of a circadian adrenal corticosterone rhythm following suprachiasmatic lesions in the rat. Brain Res 42: 201-206, 1972.
8. Moore-Ede, M. C. The circadian timing system in mammals: Two pacemakers preside over many secondary oscillators, Fed Proc, in press, 1983. 9. Moore-Ede, M. C., F. M. Sulzman and C. A. Fuller. The Clocks That Time Us: The Circadian Timhlg Sy,~tem in Mammals. Boston: Harvard University Press, 1982, pp. 1-448.
10. Pickard, G. E. The afferent connections of the suprachiasmatic nucleus of the golden hamster with emphasis on the retinohypothalamic projection. J Comp Neurol 211: 65-83, 1982. 11. Richter, C. P. "'Dark-active" rat transformed into "ligh-active'" rat by destruction of 24-hr clock: Function of 24-hr clock and synchronizers. Proc Natl Acad Sci USA 75: 6276-6280, 1978. 12. Rusak, B. Neural mechanisms of entrainment and generation of mammalian circadian rhythms. Fed Proc 38: 258%2595, 1979. 13. Rusak, B. and I. Zucker. Neural regulation of circadian rhythms. Physiol Rev 59: 445-526, 1979, 14. Stephan, F. K. and I. Zucker. Circadian rhythms in drinking behavior and locomotor activity in rats are eliminated by hypothalamic lesions. Proc Natl Acad Sci 69: 1583-1586, 1972. 15. Sulzman, F. M., C. A. Fuller and M. C. Moore-Ede. Environmental synchronizers of squirrel monkey circadian rhythms. ,f Appl Physiol 43: 795-800, 1977. 16. Tigges, J. and W. K. O'Steen. Termination of retinofugal fibers in squirrel monkey: a re-investigation using autoradiographic methods. Brain Res 79: 48%495, 1974.