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Monocular deprivation with concurrent sagittal transection of the optic chiasm
292
DeveloprnentalBrain Research. 14 ( t q ~ ~2~)? ?~,~4
BRD 60018
Monocular deprivation with concurrent sagittal transection of the optic chiasm P. E. GARRAGHTY, W. L. SALINGER and T. L. HICKEY I Department of Psychology, The University of North Carolina at Greensboro, Greensboro, NC 27412 and 1School of Optomet(v/The Medical Center, University of Alabama in Birmingham, Birmingham, A L 35294 (U.S.A.)
(Accepted February 28th, 1984) Key words: cat - - lateral geniculate nucleus - - visual deprivation - - optic chiasm transection - - cell size
We have used monocular deprivation combined with sagittal transection of the optic chiasm (MD-OX) in an attempt to separate the contributions of competitive binocular interactions from those of deprivation per se. Cell body measurements were made in the intact A1 laminae of cats reared with MD-OX. These measurements were compared to matched measurements in normally-reared cats. Cells in the deprived A1 lamina of the MD-OX cats were smaller than normal to a degree consistent with other reports involving BD and MD-E. Also consistent with the absence of competitive imbalances, cells in the non-deprived A1 lamina of these cats were normal in size, exhibiting no sign of hypertrophy. Many studies have shown that monocular deprivation has profound effects on the structure and function of the developing visual system (see Sherman and Spearn for a recent review). Separating the relative contributions of competitive binocular interactions from those of deprivation per se, however, has proven difficult to accomplish unambiguously. For example, binocular deprivation (BD), monocular deprivation with concurrent enucleation of the nondeprived eye (MD-E4, 6) and monocular deprivation combined with a circumscribed lesion of the non-deprived retina (critical segment 3) have been used to dissociate deprivation from competitive disadvantage. Questions remain, however, regarding the possible contributions of 'residual competitive imbalances '6, extraretinal disruptions 1, and sustaining lateral interactions3A 0 to the effects seen following BD, M D - E and critical segment preparations, respectively. In the present experiment, we have used monocular deprivation with sagittal transection of the optic chiasm to assess the effect of deprivation per se in the binocular segment of the lateral geniculate nucleus (LGN). With this preparation, both eyes remain intact and the critical segment is quite large. A n y changes in L G N cell anatomy and/or
physiology, therefore, are not confounded by the loss of extraretinal afferents or by sustaining lateral interactions. At 3 weeks of age, 5 cats began a period of monocular deprivation with concurrent sagittal transection of the optic chiasm ( M D - O X cats). Transection of the optic chiasm was accomplished by a transbuccal approach through the soft palate, nasopharynx and sphenoid sinus. Using an operating microscope, care was taken not to damage the adjacent structures, including the hypothalamus. Complete transection of the optic chiasm was evident through visual inspection at the time of the surgery. Subsequent anatomical analysis of the M D - O X cats revealed no obvious regions of transneuronal degeneration in the A1 laminae making it unlikely that many, if any, ipsilaterally projecting fibers were damaged. Moreover, there were no obvious patches of cells with surviving innervation in the A laminae suggesting that few, if any, contralaterally projecting fibers survived (e.g. see Fig. 1). The cross-sectional areas of L G N cells were measured in the five M D - O X cats and in three normallyreared adult cats. These measurements were made in blind-coded tissue samples from both hemispheres in
Correspondence: W. L. Salinger, Department of Psychology, The University of North Carolina at Greensboro, Greensboro, NC
27412, U.S.A. 0165-3806/84/$03.00 (~) 1984 Elsevier Science Publishers B.V.
293
Fig. 1. A representative coronal section through the lateral geniculate nucleus of an MD-OX cat. No survival of cells in lamina A, or degeneration of cells in lamina A1 is evident.
a part of the LGN just anterior to coronal 58 near the middle of the mediolateral extent of lamina A1. In each A1 lamina 100 cells were measured in successive dorsal-to-ventral and ventral-to-dorsal sweeps through the entire lamina (see Hickey et al. 4 for further methodological details). Fig. 2 presents the results of these cross-sectional area measurements. On the average, cells in the deprived A1 lamina of MD-OX cats were significantly smaller than cells in the A1 lamina of normallyreared cats (15.9%, t-test, P < 0.05). As can be seen, no difference was detected between the non-deprived and normal A1 laminae. Therefore, MD-OX results in atrophy or arrested development of cells in the deprived A1 layer, but has no detectable effect on cell size in the non-deprived A1 lamina. That is, there was no sign of hypertrophy. The absence of hypertrophy in the non-deprived A1 lamina of MD-OX cats is intriguing. Hypertrophy of geniculate cells has been observed in the non-deprived laminae of cats which were monocularly deprived 4 or treated with monocular injections of tetrodotoxin (TTX) 7. It has been hypothesized that hypertrophy might reflect abnormally large geniculocortical axonal arborizations (e.g. see Sherman and Spear11), and t h e r e is e v i d e n c e that the arbors of n o n deprived geniculocortical a x o n s a r e enlarged after
because the non-deprived eye enjoys an advantage in binocular competition for cortical synaptic sites (e.g. Hubel et al.5; Sherman and Spearll). Since contralateral inputs have been eliminated with the chiasm sec30O
c, < 250 -~
i m
200
o
150 11' L
--... N
ND Lamina A1
D
m o n o c u l a r deprivation2,5,9. Presumably in MD such
Fig. 2. A bar graph representing the results of cross-sectional area measurements made in the A1 laminae of 3 normal and 5 MD-OX cats. In each instance, the height of the bar reflects the average (+ S.E.) of the mean cell sizes in the normally-reared (N), and the MD-OX non-deprived (ND) and deprived (D) A1
expanded (or unretracted) arborizations can occur
laminae.
294 tion in the present e x p e r i m e n t , the geniculocortical axons arising from cells in the A1 lamina theoretically have relatively unchallenged access to all of the ip-
na of the M D - O X cats suggests tha~ lhis p r e p a r a m ~ has successfully eliminated binocular c o m p e l i t i ~ in~ tractions in the L G N .
silateral visual cortex, and therefore, h y p e r t r o p h y in the n o n - d e p r i v e d laminae could have been expected, The absence of h y p e r t r o p h y implies either that the geniculocortical axonal arbors in the n o n - d e p r i v e d cortex of the M D - O X cats are normal in size, and consequently, that the segregation of ocular dominance inputs proceeds normally when only m o n o c u l a r inputs are available (which seems unlikely in view of observations in enucleated monkeysS); or that some o t h e r f a c t o r ( s ) c o n t r i b u t e to L G N cell size. Finding h y p e r t r o p h y in the n o n - d e p r i v e d layers of
Previous attempts to separate the consequences of deprivation from those of competitive disadvantage (e.g. critical segment3; MD-E4. ~,) have shown diminished effects relative to deprivation coupled with competitive disadvantage (i.e. MI)4.EL). While the diminution of the effects of lid suture in those preparations could have been due to the successful separation of deprivation from competitive disadvantage, lateral interactions in the critical segment expcriment 3`m, and extraretinal disruptions in the M D - E cats' could have influenced the magnitude of the ef-
the M D cats but not in the competitively a d v a n t a g e d deprived layers of M D - E cats, Hickey et al. 4 focused on the inputs to L G N cells rather than their outputs and hypothesized that ' h y p e r t r o p h y occurs only if the eye which is at a competitive advantage also receives normal visual stimulation.' The n o n - d e p r i v e d A1 laminae of M D - O X cats in the present study clearly meet these conditions, but no h y p e r t r o p h y was observed. Since h y p e r t r o p h y has been o b s e r v e d in the non-deprived laminae of M D 4 and T T X - t r e a t e d cats 7, but is not present in the M D - O X or M D - E cats, one can speculate that the synaptic contacts present in the former two conditions permit some type of trophic interaction which cannot occur in the context of deafferentation. Thus, an additional r e q u i r e m e n t for the occurrence of h y p e r t r o p h y might be that the disadvantaged layers adjacent to the competitively advantaged, visually e x p e r i e n c e d laminae must themselves contain viable retinal terminals in o r d e r to participate in the competition which produces hypertrophy in the n o n - d e p r i v e d laminae. In any case, the absence of h y p e r t r o p h y in the n o n - d e p r i v e d lami-
fects observed. The M D - O X p r e p a r a t i o n eliminates these potential complications while, at the same time, freeing cells in the deprived lamina from cornpetitive disadvantage. We found that even when the possible roles of both lateral interactions and extraretinal influences could be excluded, m o n o c u l a r deprivation itself had an effect on cell size in the LGN. Further, the degree of cellular shrinkage found in the deprived A1 of M D - O X cats is c o m p a r a b l e to that reported for BD and M D - E cats (c.f. Fig. 7. Hickey et al.4). It would seem, therefore, that any remaining competitive imbalances after BD~ and any cxtrarctinal disruptions associated with MD-E~ are not factors involved in the control of L G N cell size. Rather, it appears parsimonious to conclude that effects of MDOX, M D - E and BD on L G N cell size are due to deprivation per se.
1 Crewther, D. P., Crewther, S. G. and Pettigrew, J. D., A role for extraocular afferents in post-critical period reversal of monocular deprivation, J. Physiol. (Lond.), 282 (1978) 181-195. 2 Friedlander, M. J. and Vahle-Hinz, C., The effects of monocular eyelid suture on the terminal arborizations of physiologically identified geniculocortical axons, SOCr Neurosci. Abstr., 8 (1982) 2. 3 Guillery, R. W., Binocular competition in the control of geniculate cell growth, J. comp. Neurol., 144 (1972) 117-127. 4 Hickey, T. L., Spear, P. D. and Kratz, K. E., Quantitative studies of cell size in the cat's dorsal lateral geniculate nucleus following visual deprivation, J. comp. Neurol., 172 (1977)265-282. 5 Hubel, D. H., Wiesel, T. N. and LeVay, S., Plasticity ofocular dominance columns in monkey striate cortex, Phil. Trans. B, 278(1977)377-409. 6 Kratz, K. E. and Spear, P. D., Effects of visual deprivation
and alterations in binocular competition on responses of striate cortex neurons in the cat, J. comp. Neurol,, 170 (1976) 141-152. 7 Kuppermann, B., Mechanisms involved in the control ot LGN cell size in the cat, Invest. Ophthalmol.. Suppl.. 24 (1983) 225. 8 Sanderson, K. J., The projection of the visual field to the lateral geniculate and medial interlaminar nuclei in the cat. J. comp. Neurol., 143 (1971) 101-117. 9 Shatz, C. J. and Stryker, P., Ocular dominance in layer IV of the cat's visual cortex and the effects of monocular deprivation, J. Physiol. (Lond.), 281 (1978) 267-283. 10 Sherman, S. M. and Guillery, R. W., Behavioral studies of binocular competition in cats, Vision Res., 16 (1976) 1479-1481. 11 Sherman, S. M. and Spear, P. D., Organization of visual pathways in normal and visually deprived cats, Physiol. Re~. 62 (1982) 738-855.
S u p p o r t e d by N . I , H . G r a n t EY01338 to T . L . t t . , EY03039 ( C O R E ) , and U N C G - R C G 7424 to W . L . S . W e thank Ken Hamrick and Isabel Ragland for their technical assistance.
DeveloprnentalBrain Research. 14 ( t q ~ ~2~)? ?~,~4
BRD 60018
Monocular deprivation with concurrent sagittal transection of the optic chiasm P. E. GARRAGHTY, W. L. SALINGER and T. L. HICKEY I Department of Psychology, The University of North Carolina at Greensboro, Greensboro, NC 27412 and 1School of Optomet(v/The Medical Center, University of Alabama in Birmingham, Birmingham, A L 35294 (U.S.A.)
(Accepted February 28th, 1984) Key words: cat - - lateral geniculate nucleus - - visual deprivation - - optic chiasm transection - - cell size
We have used monocular deprivation combined with sagittal transection of the optic chiasm (MD-OX) in an attempt to separate the contributions of competitive binocular interactions from those of deprivation per se. Cell body measurements were made in the intact A1 laminae of cats reared with MD-OX. These measurements were compared to matched measurements in normally-reared cats. Cells in the deprived A1 lamina of the MD-OX cats were smaller than normal to a degree consistent with other reports involving BD and MD-E. Also consistent with the absence of competitive imbalances, cells in the non-deprived A1 lamina of these cats were normal in size, exhibiting no sign of hypertrophy. Many studies have shown that monocular deprivation has profound effects on the structure and function of the developing visual system (see Sherman and Spearn for a recent review). Separating the relative contributions of competitive binocular interactions from those of deprivation per se, however, has proven difficult to accomplish unambiguously. For example, binocular deprivation (BD), monocular deprivation with concurrent enucleation of the nondeprived eye (MD-E4, 6) and monocular deprivation combined with a circumscribed lesion of the non-deprived retina (critical segment 3) have been used to dissociate deprivation from competitive disadvantage. Questions remain, however, regarding the possible contributions of 'residual competitive imbalances '6, extraretinal disruptions 1, and sustaining lateral interactions3A 0 to the effects seen following BD, M D - E and critical segment preparations, respectively. In the present experiment, we have used monocular deprivation with sagittal transection of the optic chiasm to assess the effect of deprivation per se in the binocular segment of the lateral geniculate nucleus (LGN). With this preparation, both eyes remain intact and the critical segment is quite large. A n y changes in L G N cell anatomy and/or
physiology, therefore, are not confounded by the loss of extraretinal afferents or by sustaining lateral interactions. At 3 weeks of age, 5 cats began a period of monocular deprivation with concurrent sagittal transection of the optic chiasm ( M D - O X cats). Transection of the optic chiasm was accomplished by a transbuccal approach through the soft palate, nasopharynx and sphenoid sinus. Using an operating microscope, care was taken not to damage the adjacent structures, including the hypothalamus. Complete transection of the optic chiasm was evident through visual inspection at the time of the surgery. Subsequent anatomical analysis of the M D - O X cats revealed no obvious regions of transneuronal degeneration in the A1 laminae making it unlikely that many, if any, ipsilaterally projecting fibers were damaged. Moreover, there were no obvious patches of cells with surviving innervation in the A laminae suggesting that few, if any, contralaterally projecting fibers survived (e.g. see Fig. 1). The cross-sectional areas of L G N cells were measured in the five M D - O X cats and in three normallyreared adult cats. These measurements were made in blind-coded tissue samples from both hemispheres in
Correspondence: W. L. Salinger, Department of Psychology, The University of North Carolina at Greensboro, Greensboro, NC
27412, U.S.A. 0165-3806/84/$03.00 (~) 1984 Elsevier Science Publishers B.V.
293
Fig. 1. A representative coronal section through the lateral geniculate nucleus of an MD-OX cat. No survival of cells in lamina A, or degeneration of cells in lamina A1 is evident.
a part of the LGN just anterior to coronal 58 near the middle of the mediolateral extent of lamina A1. In each A1 lamina 100 cells were measured in successive dorsal-to-ventral and ventral-to-dorsal sweeps through the entire lamina (see Hickey et al. 4 for further methodological details). Fig. 2 presents the results of these cross-sectional area measurements. On the average, cells in the deprived A1 lamina of MD-OX cats were significantly smaller than cells in the A1 lamina of normallyreared cats (15.9%, t-test, P < 0.05). As can be seen, no difference was detected between the non-deprived and normal A1 laminae. Therefore, MD-OX results in atrophy or arrested development of cells in the deprived A1 layer, but has no detectable effect on cell size in the non-deprived A1 lamina. That is, there was no sign of hypertrophy. The absence of hypertrophy in the non-deprived A1 lamina of MD-OX cats is intriguing. Hypertrophy of geniculate cells has been observed in the non-deprived laminae of cats which were monocularly deprived 4 or treated with monocular injections of tetrodotoxin (TTX) 7. It has been hypothesized that hypertrophy might reflect abnormally large geniculocortical axonal arborizations (e.g. see Sherman and Spear11), and t h e r e is e v i d e n c e that the arbors of n o n deprived geniculocortical a x o n s a r e enlarged after
because the non-deprived eye enjoys an advantage in binocular competition for cortical synaptic sites (e.g. Hubel et al.5; Sherman and Spearll). Since contralateral inputs have been eliminated with the chiasm sec30O
c, < 250 -~
i m
200
o
150 11' L
--... N
ND Lamina A1
D
m o n o c u l a r deprivation2,5,9. Presumably in MD such
Fig. 2. A bar graph representing the results of cross-sectional area measurements made in the A1 laminae of 3 normal and 5 MD-OX cats. In each instance, the height of the bar reflects the average (+ S.E.) of the mean cell sizes in the normally-reared (N), and the MD-OX non-deprived (ND) and deprived (D) A1
expanded (or unretracted) arborizations can occur
laminae.
294 tion in the present e x p e r i m e n t , the geniculocortical axons arising from cells in the A1 lamina theoretically have relatively unchallenged access to all of the ip-
na of the M D - O X cats suggests tha~ lhis p r e p a r a m ~ has successfully eliminated binocular c o m p e l i t i ~ in~ tractions in the L G N .
silateral visual cortex, and therefore, h y p e r t r o p h y in the n o n - d e p r i v e d laminae could have been expected, The absence of h y p e r t r o p h y implies either that the geniculocortical axonal arbors in the n o n - d e p r i v e d cortex of the M D - O X cats are normal in size, and consequently, that the segregation of ocular dominance inputs proceeds normally when only m o n o c u l a r inputs are available (which seems unlikely in view of observations in enucleated monkeysS); or that some o t h e r f a c t o r ( s ) c o n t r i b u t e to L G N cell size. Finding h y p e r t r o p h y in the n o n - d e p r i v e d layers of
Previous attempts to separate the consequences of deprivation from those of competitive disadvantage (e.g. critical segment3; MD-E4. ~,) have shown diminished effects relative to deprivation coupled with competitive disadvantage (i.e. MI)4.EL). While the diminution of the effects of lid suture in those preparations could have been due to the successful separation of deprivation from competitive disadvantage, lateral interactions in the critical segment expcriment 3`m, and extraretinal disruptions in the M D - E cats' could have influenced the magnitude of the ef-
the M D cats but not in the competitively a d v a n t a g e d deprived layers of M D - E cats, Hickey et al. 4 focused on the inputs to L G N cells rather than their outputs and hypothesized that ' h y p e r t r o p h y occurs only if the eye which is at a competitive advantage also receives normal visual stimulation.' The n o n - d e p r i v e d A1 laminae of M D - O X cats in the present study clearly meet these conditions, but no h y p e r t r o p h y was observed. Since h y p e r t r o p h y has been o b s e r v e d in the non-deprived laminae of M D 4 and T T X - t r e a t e d cats 7, but is not present in the M D - O X or M D - E cats, one can speculate that the synaptic contacts present in the former two conditions permit some type of trophic interaction which cannot occur in the context of deafferentation. Thus, an additional r e q u i r e m e n t for the occurrence of h y p e r t r o p h y might be that the disadvantaged layers adjacent to the competitively advantaged, visually e x p e r i e n c e d laminae must themselves contain viable retinal terminals in o r d e r to participate in the competition which produces hypertrophy in the n o n - d e p r i v e d laminae. In any case, the absence of h y p e r t r o p h y in the n o n - d e p r i v e d lami-
fects observed. The M D - O X p r e p a r a t i o n eliminates these potential complications while, at the same time, freeing cells in the deprived lamina from cornpetitive disadvantage. We found that even when the possible roles of both lateral interactions and extraretinal influences could be excluded, m o n o c u l a r deprivation itself had an effect on cell size in the LGN. Further, the degree of cellular shrinkage found in the deprived A1 of M D - O X cats is c o m p a r a b l e to that reported for BD and M D - E cats (c.f. Fig. 7. Hickey et al.4). It would seem, therefore, that any remaining competitive imbalances after BD~ and any cxtrarctinal disruptions associated with MD-E~ are not factors involved in the control of L G N cell size. Rather, it appears parsimonious to conclude that effects of MDOX, M D - E and BD on L G N cell size are due to deprivation per se.
1 Crewther, D. P., Crewther, S. G. and Pettigrew, J. D., A role for extraocular afferents in post-critical period reversal of monocular deprivation, J. Physiol. (Lond.), 282 (1978) 181-195. 2 Friedlander, M. J. and Vahle-Hinz, C., The effects of monocular eyelid suture on the terminal arborizations of physiologically identified geniculocortical axons, SOCr Neurosci. Abstr., 8 (1982) 2. 3 Guillery, R. W., Binocular competition in the control of geniculate cell growth, J. comp. Neurol., 144 (1972) 117-127. 4 Hickey, T. L., Spear, P. D. and Kratz, K. E., Quantitative studies of cell size in the cat's dorsal lateral geniculate nucleus following visual deprivation, J. comp. Neurol., 172 (1977)265-282. 5 Hubel, D. H., Wiesel, T. N. and LeVay, S., Plasticity ofocular dominance columns in monkey striate cortex, Phil. Trans. B, 278(1977)377-409. 6 Kratz, K. E. and Spear, P. D., Effects of visual deprivation
and alterations in binocular competition on responses of striate cortex neurons in the cat, J. comp. Neurol,, 170 (1976) 141-152. 7 Kuppermann, B., Mechanisms involved in the control ot LGN cell size in the cat, Invest. Ophthalmol.. Suppl.. 24 (1983) 225. 8 Sanderson, K. J., The projection of the visual field to the lateral geniculate and medial interlaminar nuclei in the cat. J. comp. Neurol., 143 (1971) 101-117. 9 Shatz, C. J. and Stryker, P., Ocular dominance in layer IV of the cat's visual cortex and the effects of monocular deprivation, J. Physiol. (Lond.), 281 (1978) 267-283. 10 Sherman, S. M. and Guillery, R. W., Behavioral studies of binocular competition in cats, Vision Res., 16 (1976) 1479-1481. 11 Sherman, S. M. and Spear, P. D., Organization of visual pathways in normal and visually deprived cats, Physiol. Re~. 62 (1982) 738-855.
S u p p o r t e d by N . I , H . G r a n t EY01338 to T . L . t t . , EY03039 ( C O R E ) , and U N C G - R C G 7424 to W . L . S . W e thank Ken Hamrick and Isabel Ragland for their technical assistance.