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Asymmetric distribution of side preference in hamsters can be reversed by lesions of the caudate nucleus
Be/~o~~ioura/
Brain
Research,
Q Elsevier/North-Holland
I ( 1980)
Biomedical
187
196
187
Press
ASYMMETRIC DISTRIBUTION OF SIDE PREFERENCE IN HAMSTERS CAN BE REVERSED BY LESIONS OF THE CAUDATE NUCLEUS
T. GIEHRL
and H. DISTEL
(Received November 7th. 1979) (Accepted December 5th. 1979) Kq. n~ortlv:
asymmetry-caudatc
nucleus-laterality-lesions-sensorimotorcortex-side
preference
SUMMARY
Side preferences were tested in Syrian hamsters (Mesocricetus auratus) by placing them on an elevated centerboard which divided a rectangular arena in two equal compartments. When descending from the centerboard all animals turned more often right (79”/,) than left (217;). After small electrolytic lesions of the left caudate nucleus the side preference was reversed: 31% to the right and 69% to the left. Combined lesions of the left caudate nucleus and left sensorimotor cortex showed similar results; lesions of the left cortex alone had only minor effects. These observations support the hypothesis [28] that side preferences depend on asymmetries of the nigrostriatal system.
INTRODUCTION
The locomotion ofanimals is generally considered to be directed by external stimuli only, and in absence of such stimuli to be randomly but symmetrically distributed to both sides of the body. However, it has been demonstrated in bias-free environments, that rats and other rodents display spontaneous directional preferences which vary among individuals [ 151, and that such preferences may correlate with handedness in an operant task [ 121. The question of functional lateralization has been studied over the years in a number of mammalian species mainly by determining handedness. The results show. differently from man,
188 that the proportion of left and right handed individuals is roughly equal [9]. Yet, in the course of a study on visual cliff behavior it was noted that hamsters turned consistently more right thari left [IO]. Therefore, we decided to study the phenomenon in an improved setup, and to investigate possible effects of brain lesions.
Fifty-three Syrian hamsters (Me.socricerus aurafus, 22 males, 3 1 females) were tested in the present study. All were laboratory bred except 6 juveniles which were purchased from a local dealer. They were housed separately with food and water ad libitum, and kept under an artificial 12 h day. At the time of testing, 25 of the animals were 6 weeks old, the others were adult. The floor of a commercially available visual cliff apparatus (Lafayette Instruments Co., Lafayette, Ind.) was raised to equal level on both sides. Thereby a square arena was yielded (75 x 75 cm with 20 cm walls) which was painted with a red-white, 5 x 5 cm chequer-board pattern. The grey centerboard (75 x 10 cm) which divided the arena in equal compartments was fixed 6 cm above the floor. The boards were covered with panes of glass. For testing the animal was placed in the middle of the centerboard by means of an inverted tin to ensure, after lifting of the tin, an unbiased starting position. The animal was allowed to walk freely on the centerboard, and to descend to either side of the arena. After the descent, or after 5 min, it was returned to the home cage. Each animal was given a total of 12 or 15 trials, 3-4 trials per day with an intertrial interval of 60-90 min. In order to minimize extraneous cues, several precautions were taken : The apparatusand the light source (60 W, 50 cm above the centerboard) were covered with a gauze curtain which allowed sufficient view from the dark outside but not from the inside of the apparatus. After each trial, the apparatus was rotated 90” to exclude possible directing stimuli from the laboratory, and thoroughly cleaned (isopropanol 20%) to remove odor traces, and the boards were turned around and over. Finally, some experiments were conducted in another laboratory for control. Lesions of cortex and/or caudate nucleus were carried out in 17 adult hamsters which had been previously tested for side preference, and 13 neonate animals under pentobarbital (80 mg/kg) or ether anesthesia respectively. After a midline skin incision, a small opening (l-3 mm) was made in the cranial bone over one hemisphere through which brain tissue was aspirated by means of a suction pipette, or an electrode was lowered for small electrolytic lesions of the caudate nucleus (1 mA for 10 set). In 8 neonate animals, the cranial bone was left intact, and a heated probe (2 mm in diameter) was pressed against the skull in order to yield selective lesions of the cortex [ 191. Alicr suturing the skin
189 wdund, the adult animals were allowed to recover for 3 days before testing. Neonatally lesioned animals were tested al the age of 6 weeks. After testing, all experimental animals were anesthetized and perfused with 4?;, formaldehyde solution. Frozen sections of the brains were Nissl-stained and microscopically controlled for lesions. Drawings of the reconstructed lesion sides were superimposed on Xerox sheets of an atlas which was prepared from a normal hamster brain [21]. The data were analyzed statistically using the X2-test. RESULTS
Placed on the centerboard of the testing arena, the hamsters behaved in a similar way: they started to run back and forth along the edges of the centerboard, and after some time had elapsed. they looked more often towards the floor of the arena. Then, usually at the end of the board, they oriented the body parallel to the wall, made a few steps on the spot, and descended. Recorded was the side of descent with respect to the body. normal
lesioned
hamsters
hamsters
left caudate OtllY
,.ll
r4pkt 5
Fig.
0
I.
animals; light
Variation horizontal
: no descents.
I.11
IO
5
of
side axis:
IO
preference number
in
normal
of lrials:
kind
hatched:
* 5
Iesioned
hamsters.
left
descents:
side
0
Vertical dark:
IO
5
axis: right
side
individual descenls:
190 In order to assess a baseline for left-right preference, 28 adult hamsters of both sexes were given 336 trials; i.e. 12 trials each. Two of the animals failed to descend from the board in 15 of their 24 trials. %l animals went more often to the right side, although, on some trials, they also turned to the left. There was no individual which preferred the left side (Fig. 1). Sixty-eight left and 253 right turns were counted which corresponds to 21 ?d and 79% respectively. No significant difference was found in the left-right ratio among both sexes (20:80x in males, 21:79”/d in females). Since the experiments described below involved adult as well as 6-week-old animals, a juvenile control group was selected from our breed and given the same testing. In addition, juvenile animals obtained from another breeder were matched with this group in order to test for possible genetic differences. It was found that the animals of both groups and the adult animals behaved almost identically in the testing situation (see Table I). Finally, 15 of the 28 adult animals were tested in the visual cliff situation with one side of the arena at 53 cm depth, the other side at 6 cm as before. We found that despite this asymmetry of the apparatus, the ratio of right-left descents remained the same (Table I). However, in 16’4 of the trials the animals had not descended from the centerboard within the 5 min period.
TABLE If
7)pe
I qle\-perimetrt
Trials
DiWCW IS 110
Normal
28 6 6 I5
leji
rig/ii
w
righ
animals
adult hamsters juveniles, own bred juveniles. diff. bred adult hamsters, visual cliff
Lesioned
Ratio
21%
79”/ 0 **
22% 19%
78=‘/’**
336 72 72 180
I5 3 3 29
68 I5 I3 31
253 54 56 120
21%
8&* 79%**
30
-
7
23
23%
779’* ,,,a
120
3
74
43
63%
37”/o **
I44 96
6 I
II0 32
28 63
69% 34%
3i”/* 66$
animals
2 right cortex and right caudate nucleus 8 left cortex and left caudate nucleus I2 left caudate nucleus only 8 left cortex only * P d 0.005. ** P 60.001.
191 Lesiorn experimenrs Ten animals received combined lesions of cortex and caudatum, 2 to the right hemisphere and 8 to the left hemisphere. When tested in the apparatus on 15 trials each, the lesioned animals were indistinguishable in their overall behavior from normal animals. The right side-lesioned animals showed no significant difference in their left-right ratio from normal animals (Table I). In the left side-lesioned animals, however, the left-right preference was almost
b
Fig. 2. Schematic drawing of the reconstructed lesion sides. Dark: smallest lesion; hatched: largest lesion; numberscorrespond to mm anterior IO brcgma. a: suction lesions of the right cortex and right caudate nucleus. b: electrolytic lesions of the left cortex and left caudate nucleus. c: heat lesions of the left cortex.
192 reversed. In 63”,, of the 120 trials, these animals turned to the left side before descending. and in 37”,, of the trials to the right side. Five of the left side-lesioned animals were lesioned as neonates and tested as juveniles whereas 3 animals were lesioned and tested as adults. As before, both subgroups had about the same percentage of left-right descent (64”,, and and histological 36”,, in juveniles, 62”” and X3”,, in adults). Macroscopical examination of thu brains demonstrated that tissue of the somatosensory cortex as well as parts of the underlying caudate nucleus were removed (Fig. 2a). In 2 cases the hippocampus was also partially damaged. In order to differentiate between what effected the reversal of the side preference, 12 animals received lesions of the left caudatum. Each animal was given I2 trials. The results clearly revealed that left striatum lesions alone were
Fig.
3. Dark-field
myelinakd
micrograph
libersappearwhite.
ora The
brain arrow
section points
demonstrating LO
a
electrolylic
a Icsion lesion
in thccaudaw sile.
nucleus
(CN):
193 sufficient if not slightly superior in reversing the side preference: 69”/, of the descents were to the left side and 3 1“/A to the right side. Left cortical lesions, however, had only a minor, although significant effect upon the side preference: 349; of the descents were to the left side and 66”/, to the right side. The brains of the caudate-lesioned animals appeared macroscopically normal, yet, in Nissl-stained sections the small electrolytic lesions could be well detected. They were confined to the head of the caudate nucleus and did not involve cortical tissue (Figs. 2b and 3). In all cortex-lesioned animals, the left hemisphere appeared slightly shrunken, and lesion sites were not always macroscopically visible. This was probably due to the fact that the lesions were performed 6 weeks earlier, shortly after birth. Microscopic comparison of the hemispheres demonstrated that the caudate nuclei on both sides were of equal size and not affected by the lesion. Yet the reconstruction of the intact parts of the left hemisphere allowed a fairly good estimate of the missing somatosensory cortex (Fig. 2~). Although the size of combined or selective lesions of cortex and caudatum varied somewhat among animals of the same group, there was no significant difference or trend in the left-right performance which could be ascribed to the amount of lesioned tissue. DISCUSSION
The present findings suggest that exploring hamsters preferentially turn toward the right side when given a choice, as in our testing situation. It seems unlikely that this preference was due to environmental cues from the laboratory or the apparatus since all possible precautions had been taken (Methods). Further, when an environmental bias was introduced by lowering one side of the arena more than the other, the ratio of left versus right descents was not changed (Table I). All this indicated that the observed side preference was of endogeneous origin. The assumption was confirmed by lesions to the left hemisphere of the hamster brain which indeed affected the right side preference. Spontaneous side preferences have been hitherto investigated by Glick and co-workers with various methods [I 51. For example, rats, mice and gerbils display individual preferences for the left or the right side when tested in a two-lever operant chamber [ 121, in a T-maze [ 14. 281 or in an automated rotometer [ 171. In agreement with our lesion experiments, they found in rats that side preferences can be reversed by unilateral lesions of the opposite striatum. Furthermore, spontaneous side preferences were correlated with an intrinsic symmetry in the bilateral content of striatal dopamine [28]. Drugs which facilitate dopaminergic transmission, e.g. Bamphetamine and apomorphine, may potentiate this asymmetry and induce rotation in the spontaneously preferred direction [13-l 7, 281. Rotational behavior has been repeatedly induced in rats
194 and mice by unilateral lesions [7, 20, 22, 231 and unilateral stimulation [2, 3, 24, 271, or by pharmacological manipulation [l, 22-251 of the substantia nigra and the corpus striatum. Taken together, these experiments support the hypothesis that side preferences in rodents are caused by a bilateral functional asymmetry of the nigrostriatal system [15, 281. We found in hamsters that electrolytic lesions to the left caudate nucleus reversed the right side preference. Because lesions of the caudate nucleus inevitably involve fibers of passage to and from neocortex, damage to them may have caused the reversal (cf. Fig. 3). However, lesions of the left sensorimotor cortex did not change the side preference, and combined lesions of the caudate nucleus and the overlying sensorimotor cortex had no more effect than caudate lesions alone (Table I). Thus, the reversal of the side preference may be solely attributed to the destruction of caudate tissue. The neocortex projects topographically to the neostriatum [5, 261. The observed small decrease in right side preference after lesions of the opposite cortex may, therefore, be explained by the loss of cortical afferentation to the caudate nucleus. It has been reported that unilateral lesions of the frontal, but not of the posterior, cortex affect amphetamine-induced rotational behavior in rats [1 11. Consequently, the degree of side preference may change in relation to the cortical area which has been lesioned. As mentioned above, the proportion of left- and right-handed animals seems to be roughly equal in all tested species [9]. A similar conclusion can be drawn from the published data on spontaneous side preferences in rodents [12, 14, 171. In humans, however, the distribution of handedness is asymmetric, and the incidence of left-handedness may vary from 0.6% in Katanganese to 11.3% in Eskimo societies [8]. There is little evidence for a simple Mendelian inheritance of handedness [6], and the problem of genetic versus environmental determination is still much debated [9]. Since the housing of our hamsters was standard for laboratory rodents, an environmental determination of the uniform right side preference seems unlikely. Yet the testing population was small, and it is possible that strain differences may exist with regard to the incidence of a left side preference. Still, there are other species for which a complete one-sided distribution of brain asymmetries have been reported: in Canary birds, the neural control of vocalization is completely lateralized [ 181, and in frogs, the left habenula nucleus is double while the right one is single [4]. ACKNOWLEDGEMENTS
The authors express their thanks to Professor Ernst Piippel and Dr. Wolfgang Fries for discussion and suggestions; to Ms. Inge Briigelmann and Ms. Karin Haupt for assistance with histology and art work, and to Ms. Petra Mitterhusen for secretarial help.
195 REFERENCES Andin N.E., Dahlstrom, A., Fuxe, K. and Larsson, K., Functional role of the nigro-neostriatal dopamine neurons, Acra pharrnacol. (KM.), 24 (1966) 263-274. 2 Arbuthnott. G.W. and Crow, T.J. Relation of contraversive turning to unilateral release of dopamine from the nigro-striatal pathway in rats, hp. Newel., 30 (1971) 484-491. G.W. and Ungerstedt, U., Locomotor behavior after electrical stimulation of 3 Arbuthnott. dopamine containing neurones, Acra physiol. stand., Suppl. 330 (I 969) I 17. V. and Kemali, M., Exceptions to bilateral symmetry in the epithalamus of 4 Braitenberg, lower vertebrates. J. camp. Neural., 138 (1970) 137-146. 5 Carman, J.B., Cowan, W.M. and Powell. T.P.S., The organization of cortico-striate connexions in the rabbit, Bruin. 86 (I 963) 525-562. 6 Collins, R.L., Toward an admissible genetic model for the inheritance of degree and direction of asymmetry. In S. Harnad et al. (Eds.), Lureralizariotl ill rite Nervous Qsrern, Academic Press, New York. pp. 137-I 50. 7 Crow. T.J., The relationship between lesion site, dopamine neurons and turning behavior in the rat, Esp. Newel.. 32 (1971) 347-355. perspective on the evolution and lateralization of the 8 Dawson, J.L.M., An anthropological brain, Ann. N. Y. Acad. Sci.. 299 (1977) 424-447. 9 Dimond. S.J., Evolution and lateralization of the brain: Concluding remarks, Ann. N.Y. Acad. Sci., 299 (1977) 477-501. 10 Giehrls. T.. Seire,lbr\tor-Igu,lg hei Nornden wd Hirnverle/zrerl Hantsrern, Thesis, Mtinchen. I
1980. II I2 13
14
15 16 17 18 19 20 21 22
Click, SD. and Greenstein. S.. Possible modulating influence of frontal cortex on nigrostriate function, Brit. J. P/~anmcol.. 49 (1973) 316-321. Click, SD. and Jerussi, T.P., Spatial and paw preference in rats: Their relationship to ratedependent effects of d-aphetamine, J. Phamucol. esp. Ther.. 188 (1974) 714-725. Click, S.D., Jerussi. T.P.. Waters, D.H. and Green, J.P.. Amphetamine-induced changes in striatal dopamine and acetylcholine and relationship to rotation (circling behavior) in rats, Biochenl. Plwrntacol.. 23 (1974) 3223-3225. Glick. S.D., Zimmerberg, B. and Greenstein. S.. Individual differences among mice in normal and amphetamine-enhanced locomotor activity: relationship to behavioral indices of striatal asymmetry, Bruin Res.. 105 (1976) 362-364. Glick, SD.. Zimmerberg. B. and Jerussi, T.P., Adaptive significance of laterality in the rodent, Ann. N. Y. Acucl. Sri., 299 (1977) 180-185. Jerussi, T.P. and Glick. S.D., Apomorphine-induced rotation in normal rats and interaction with unilateral caudate lesions, Ps?.c/rop/mrn?rrco/ugiu (Bed.), 40 (1975) 329-334. Jerussi. T.P. and Glick. S.D., Spontaneous and drug-induced rotation (circling behavior) in the mongolian gerbil (Meriones wguicdarus), Belruv. Biol.. I6 (1976) 241-244. Nottebohm. F., Asymmetries in neural control of vocalization in the canary. In S. Harnard et al. (Eds.). Lurerulizuriof~ ijr I/I~ Nervous Sj,sre~n. Academic Press, New York, 19.77. Schneider, G.E., Early lesions of superior colliculus: factors affecting the formation of abnormal retinal projections, Brairl Behav. Eeol., 8 (1973) 73-109. Schwartz, W.J., Gunn, R.H.. Sharp, F.R. and Evarts, E.V., Unilateral electrolytic lesions of the substantia nigra cause contralateral circling in rats, Brain Res., I05 (I 976) 358-361. Smith, O.A. and Bodemer, C.N., A stereotaxis atlas of the brain of the golden hamster (Mesocricem auralus), J. cornp. Neural., I20 (1963) 53-63. Ungerstedt. U., Striatal dopamine release after amphetamine or nerve degeneration revealed by rotational behavior, Acra ph~~siol. scard.. Suppl. 367 (1971) 49-68.
196 23
Ungcrstedt. U. and after 6-hydosydopamine
Arbuthnott. lesions
G.W.. Quantitative in the nigrostriatal
recording dopamine
of rowional system. &oi~
behavior in rats Rcs.. 24 (1970)
485-493. 24
Ungerstedt. stimulation 461-471.
25
Von Voigtlander. dopamine lesions
76
Webster, 532-547.
27
Zimmerberg. of the caudate
28
Zimmerberg. B.. Glick. S.D. and Jerussi, in rats. Sckwco. I85 (I 974) 623-625.
tamine
U.. Butcher. of dopaminergic
and other K.E..
L.L..
Butcher, mechanisms
P.F. and Moore. in,thc striatum: psychomotor Cortico-strintal
S.G.. And&. N.E. in the neostriatum
K.E.. Turning behavior Effects of apomorphinc.
stimulants.
and Fuse. of the rat, of mice with L-DOPA.
Nntro~lrcf,,llmca/o~~,.
interrelations
in the albino
B. and Click. S-D.. Changes in side nucleus in rats. Brain Ras.. 56 (1975) T.P..
prcfcrences 335-335.
Neurochemical
K.. Bark
rat.
Direct Rc.s..
unilateral 6-hydrosyamantadine. amphe-
I2 ( 1973)
45 l-462.
J. Awr.
~Lo/rc/.~.
during correlate
chemical I4 (1969)
unilateral of a spatial
95 (1961) stimulation preference
Brain
Research,
Q Elsevier/North-Holland
I ( 1980)
Biomedical
187
196
187
Press
ASYMMETRIC DISTRIBUTION OF SIDE PREFERENCE IN HAMSTERS CAN BE REVERSED BY LESIONS OF THE CAUDATE NUCLEUS
T. GIEHRL
and H. DISTEL
(Received November 7th. 1979) (Accepted December 5th. 1979) Kq. n~ortlv:
asymmetry-caudatc
nucleus-laterality-lesions-sensorimotorcortex-side
preference
SUMMARY
Side preferences were tested in Syrian hamsters (Mesocricetus auratus) by placing them on an elevated centerboard which divided a rectangular arena in two equal compartments. When descending from the centerboard all animals turned more often right (79”/,) than left (217;). After small electrolytic lesions of the left caudate nucleus the side preference was reversed: 31% to the right and 69% to the left. Combined lesions of the left caudate nucleus and left sensorimotor cortex showed similar results; lesions of the left cortex alone had only minor effects. These observations support the hypothesis [28] that side preferences depend on asymmetries of the nigrostriatal system.
INTRODUCTION
The locomotion ofanimals is generally considered to be directed by external stimuli only, and in absence of such stimuli to be randomly but symmetrically distributed to both sides of the body. However, it has been demonstrated in bias-free environments, that rats and other rodents display spontaneous directional preferences which vary among individuals [ 151, and that such preferences may correlate with handedness in an operant task [ 121. The question of functional lateralization has been studied over the years in a number of mammalian species mainly by determining handedness. The results show. differently from man,
188 that the proportion of left and right handed individuals is roughly equal [9]. Yet, in the course of a study on visual cliff behavior it was noted that hamsters turned consistently more right thari left [IO]. Therefore, we decided to study the phenomenon in an improved setup, and to investigate possible effects of brain lesions.
Fifty-three Syrian hamsters (Me.socricerus aurafus, 22 males, 3 1 females) were tested in the present study. All were laboratory bred except 6 juveniles which were purchased from a local dealer. They were housed separately with food and water ad libitum, and kept under an artificial 12 h day. At the time of testing, 25 of the animals were 6 weeks old, the others were adult. The floor of a commercially available visual cliff apparatus (Lafayette Instruments Co., Lafayette, Ind.) was raised to equal level on both sides. Thereby a square arena was yielded (75 x 75 cm with 20 cm walls) which was painted with a red-white, 5 x 5 cm chequer-board pattern. The grey centerboard (75 x 10 cm) which divided the arena in equal compartments was fixed 6 cm above the floor. The boards were covered with panes of glass. For testing the animal was placed in the middle of the centerboard by means of an inverted tin to ensure, after lifting of the tin, an unbiased starting position. The animal was allowed to walk freely on the centerboard, and to descend to either side of the arena. After the descent, or after 5 min, it was returned to the home cage. Each animal was given a total of 12 or 15 trials, 3-4 trials per day with an intertrial interval of 60-90 min. In order to minimize extraneous cues, several precautions were taken : The apparatusand the light source (60 W, 50 cm above the centerboard) were covered with a gauze curtain which allowed sufficient view from the dark outside but not from the inside of the apparatus. After each trial, the apparatus was rotated 90” to exclude possible directing stimuli from the laboratory, and thoroughly cleaned (isopropanol 20%) to remove odor traces, and the boards were turned around and over. Finally, some experiments were conducted in another laboratory for control. Lesions of cortex and/or caudate nucleus were carried out in 17 adult hamsters which had been previously tested for side preference, and 13 neonate animals under pentobarbital (80 mg/kg) or ether anesthesia respectively. After a midline skin incision, a small opening (l-3 mm) was made in the cranial bone over one hemisphere through which brain tissue was aspirated by means of a suction pipette, or an electrode was lowered for small electrolytic lesions of the caudate nucleus (1 mA for 10 set). In 8 neonate animals, the cranial bone was left intact, and a heated probe (2 mm in diameter) was pressed against the skull in order to yield selective lesions of the cortex [ 191. Alicr suturing the skin
189 wdund, the adult animals were allowed to recover for 3 days before testing. Neonatally lesioned animals were tested al the age of 6 weeks. After testing, all experimental animals were anesthetized and perfused with 4?;, formaldehyde solution. Frozen sections of the brains were Nissl-stained and microscopically controlled for lesions. Drawings of the reconstructed lesion sides were superimposed on Xerox sheets of an atlas which was prepared from a normal hamster brain [21]. The data were analyzed statistically using the X2-test. RESULTS
Placed on the centerboard of the testing arena, the hamsters behaved in a similar way: they started to run back and forth along the edges of the centerboard, and after some time had elapsed. they looked more often towards the floor of the arena. Then, usually at the end of the board, they oriented the body parallel to the wall, made a few steps on the spot, and descended. Recorded was the side of descent with respect to the body. normal
lesioned
hamsters
hamsters
left caudate OtllY
,.ll
r4pkt 5
Fig.
0
I.
animals; light
Variation horizontal
: no descents.
I.11
IO
5
of
side axis:
IO
preference number
in
normal
of lrials:
kind
hatched:
* 5
Iesioned
hamsters.
left
descents:
side
0
Vertical dark:
IO
5
axis: right
side
individual descenls:
190 In order to assess a baseline for left-right preference, 28 adult hamsters of both sexes were given 336 trials; i.e. 12 trials each. Two of the animals failed to descend from the board in 15 of their 24 trials. %l animals went more often to the right side, although, on some trials, they also turned to the left. There was no individual which preferred the left side (Fig. 1). Sixty-eight left and 253 right turns were counted which corresponds to 21 ?d and 79% respectively. No significant difference was found in the left-right ratio among both sexes (20:80x in males, 21:79”/d in females). Since the experiments described below involved adult as well as 6-week-old animals, a juvenile control group was selected from our breed and given the same testing. In addition, juvenile animals obtained from another breeder were matched with this group in order to test for possible genetic differences. It was found that the animals of both groups and the adult animals behaved almost identically in the testing situation (see Table I). Finally, 15 of the 28 adult animals were tested in the visual cliff situation with one side of the arena at 53 cm depth, the other side at 6 cm as before. We found that despite this asymmetry of the apparatus, the ratio of right-left descents remained the same (Table I). However, in 16’4 of the trials the animals had not descended from the centerboard within the 5 min period.
TABLE If
7)pe
I qle\-perimetrt
Trials
DiWCW IS 110
Normal
28 6 6 I5
leji
rig/ii
w
righ
animals
adult hamsters juveniles, own bred juveniles. diff. bred adult hamsters, visual cliff
Lesioned
Ratio
21%
79”/ 0 **
22% 19%
78=‘/’**
336 72 72 180
I5 3 3 29
68 I5 I3 31
253 54 56 120
21%
8&* 79%**
30
-
7
23
23%
779’* ,,,a
120
3
74
43
63%
37”/o **
I44 96
6 I
II0 32
28 63
69% 34%
3i”/* 66$
animals
2 right cortex and right caudate nucleus 8 left cortex and left caudate nucleus I2 left caudate nucleus only 8 left cortex only * P d 0.005. ** P 60.001.
191 Lesiorn experimenrs Ten animals received combined lesions of cortex and caudatum, 2 to the right hemisphere and 8 to the left hemisphere. When tested in the apparatus on 15 trials each, the lesioned animals were indistinguishable in their overall behavior from normal animals. The right side-lesioned animals showed no significant difference in their left-right ratio from normal animals (Table I). In the left side-lesioned animals, however, the left-right preference was almost
b
Fig. 2. Schematic drawing of the reconstructed lesion sides. Dark: smallest lesion; hatched: largest lesion; numberscorrespond to mm anterior IO brcgma. a: suction lesions of the right cortex and right caudate nucleus. b: electrolytic lesions of the left cortex and left caudate nucleus. c: heat lesions of the left cortex.
192 reversed. In 63”,, of the 120 trials, these animals turned to the left side before descending. and in 37”,, of the trials to the right side. Five of the left side-lesioned animals were lesioned as neonates and tested as juveniles whereas 3 animals were lesioned and tested as adults. As before, both subgroups had about the same percentage of left-right descent (64”,, and and histological 36”,, in juveniles, 62”” and X3”,, in adults). Macroscopical examination of thu brains demonstrated that tissue of the somatosensory cortex as well as parts of the underlying caudate nucleus were removed (Fig. 2a). In 2 cases the hippocampus was also partially damaged. In order to differentiate between what effected the reversal of the side preference, 12 animals received lesions of the left caudatum. Each animal was given I2 trials. The results clearly revealed that left striatum lesions alone were
Fig.
3. Dark-field
myelinakd
micrograph
libersappearwhite.
ora The
brain arrow
section points
demonstrating LO
a
electrolylic
a Icsion lesion
in thccaudaw sile.
nucleus
(CN):
193 sufficient if not slightly superior in reversing the side preference: 69”/, of the descents were to the left side and 3 1“/A to the right side. Left cortical lesions, however, had only a minor, although significant effect upon the side preference: 349; of the descents were to the left side and 66”/, to the right side. The brains of the caudate-lesioned animals appeared macroscopically normal, yet, in Nissl-stained sections the small electrolytic lesions could be well detected. They were confined to the head of the caudate nucleus and did not involve cortical tissue (Figs. 2b and 3). In all cortex-lesioned animals, the left hemisphere appeared slightly shrunken, and lesion sites were not always macroscopically visible. This was probably due to the fact that the lesions were performed 6 weeks earlier, shortly after birth. Microscopic comparison of the hemispheres demonstrated that the caudate nuclei on both sides were of equal size and not affected by the lesion. Yet the reconstruction of the intact parts of the left hemisphere allowed a fairly good estimate of the missing somatosensory cortex (Fig. 2~). Although the size of combined or selective lesions of cortex and caudatum varied somewhat among animals of the same group, there was no significant difference or trend in the left-right performance which could be ascribed to the amount of lesioned tissue. DISCUSSION
The present findings suggest that exploring hamsters preferentially turn toward the right side when given a choice, as in our testing situation. It seems unlikely that this preference was due to environmental cues from the laboratory or the apparatus since all possible precautions had been taken (Methods). Further, when an environmental bias was introduced by lowering one side of the arena more than the other, the ratio of left versus right descents was not changed (Table I). All this indicated that the observed side preference was of endogeneous origin. The assumption was confirmed by lesions to the left hemisphere of the hamster brain which indeed affected the right side preference. Spontaneous side preferences have been hitherto investigated by Glick and co-workers with various methods [I 51. For example, rats, mice and gerbils display individual preferences for the left or the right side when tested in a two-lever operant chamber [ 121, in a T-maze [ 14. 281 or in an automated rotometer [ 171. In agreement with our lesion experiments, they found in rats that side preferences can be reversed by unilateral lesions of the opposite striatum. Furthermore, spontaneous side preferences were correlated with an intrinsic symmetry in the bilateral content of striatal dopamine [28]. Drugs which facilitate dopaminergic transmission, e.g. Bamphetamine and apomorphine, may potentiate this asymmetry and induce rotation in the spontaneously preferred direction [13-l 7, 281. Rotational behavior has been repeatedly induced in rats
194 and mice by unilateral lesions [7, 20, 22, 231 and unilateral stimulation [2, 3, 24, 271, or by pharmacological manipulation [l, 22-251 of the substantia nigra and the corpus striatum. Taken together, these experiments support the hypothesis that side preferences in rodents are caused by a bilateral functional asymmetry of the nigrostriatal system [15, 281. We found in hamsters that electrolytic lesions to the left caudate nucleus reversed the right side preference. Because lesions of the caudate nucleus inevitably involve fibers of passage to and from neocortex, damage to them may have caused the reversal (cf. Fig. 3). However, lesions of the left sensorimotor cortex did not change the side preference, and combined lesions of the caudate nucleus and the overlying sensorimotor cortex had no more effect than caudate lesions alone (Table I). Thus, the reversal of the side preference may be solely attributed to the destruction of caudate tissue. The neocortex projects topographically to the neostriatum [5, 261. The observed small decrease in right side preference after lesions of the opposite cortex may, therefore, be explained by the loss of cortical afferentation to the caudate nucleus. It has been reported that unilateral lesions of the frontal, but not of the posterior, cortex affect amphetamine-induced rotational behavior in rats [1 11. Consequently, the degree of side preference may change in relation to the cortical area which has been lesioned. As mentioned above, the proportion of left- and right-handed animals seems to be roughly equal in all tested species [9]. A similar conclusion can be drawn from the published data on spontaneous side preferences in rodents [12, 14, 171. In humans, however, the distribution of handedness is asymmetric, and the incidence of left-handedness may vary from 0.6% in Katanganese to 11.3% in Eskimo societies [8]. There is little evidence for a simple Mendelian inheritance of handedness [6], and the problem of genetic versus environmental determination is still much debated [9]. Since the housing of our hamsters was standard for laboratory rodents, an environmental determination of the uniform right side preference seems unlikely. Yet the testing population was small, and it is possible that strain differences may exist with regard to the incidence of a left side preference. Still, there are other species for which a complete one-sided distribution of brain asymmetries have been reported: in Canary birds, the neural control of vocalization is completely lateralized [ 181, and in frogs, the left habenula nucleus is double while the right one is single [4]. ACKNOWLEDGEMENTS
The authors express their thanks to Professor Ernst Piippel and Dr. Wolfgang Fries for discussion and suggestions; to Ms. Inge Briigelmann and Ms. Karin Haupt for assistance with histology and art work, and to Ms. Petra Mitterhusen for secretarial help.
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196 23
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