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Initial hypertrophy of cells in undeprived laminar of the lateral geniculate nucleus of the monkey following early monocular visual deprivation
439
Brain Research, 238 (1982) 439-444 Elsevier Biomedical Press
Initial hypertrophy of cells in undeprived laminae of the lateral genieulate nucleus of the monkey following early monocular visual deprivation
M. P. HEADON, J. J. SLOPER and T. P. S. POWELL Department of Human Anatomy, South Parks Road, Oxford OX1 3QX (U.K.)
(Accepted January 7th, 1982) Key words: lateral geniculate nucleus -- monkey
earlyeye closure - - hypertrophy
Comparisons of mean cell area in the lateral geniculate nucleus between normal and monocularly deprived Rhesus monkeysshow that closure started in the first few days of life produces an initial hypertrophy of up to 25 ~ affecting undeprived parvocellular cells. Hypertrophy is maximal at 4 weeks. Following this there is a later shrinkage affecting both deprived and undeprived parvocellular cells so that ultimately undeprived parvocellular cells are about 10~ smaller and deprived parvocellular cells about 35 ~,, smaller than corresponding cells in normal animals. Most studies of the effect of monocular visual deprivation on the lateral geniculate nucleus (LGN) have compared the sizes of cells in the deprived LGN laminae with those of cells in the corresponding undeprived laminae of the opposite nucleus and, although limitations of this approach have been recognized, it has generally been assumed that the predominant change resulting from visual deprivation is shrinkage or 'degeneration' of cells in the deprived laminae. Comparisons with normal animals have provided some evidence for an additional degree of hypertrophy of undeprived LGN cells in the cat 7 and dog 1° but this has not been found in other studies 6,s. Late closure of an eye in the monkey has recently been found to produce marked shrinkage of cells in undeprived L G N laminae when comparisons are made between experimental and normal monkeysZ 5; this has prompted a re-examination of the changes in LGN cell size produced by monocular closure performed in the first few days of life, making comparisons between deprived and undeprived cell sizes and cell sizes from normal animals. Measurements of cell area have been made for 50 cells in each lamina of 7 infant monkeys in which the lids over one eye had been sutured under open ether anesthesia in the first few days of life and the infants returned to their mothers for various survival periods (Fig. 1). Methods of perfusion, histological preparation and cell measurement are as described previously z. The normal cell sizes used as a control in this paper are taken from a previous paper a and are from both lateral geniculate nuclei of 16 normal rhesus monkeys prepared and measured using the same techniques as in this study. For statistical analysis the mean cell size for each lamina in each animal has been treated as a single observation and group mean and standard deviations have 0006-8993/82/0000-0000/$02.75 © Elsevier Biomedical Press
440
0M167 0M380 01,4399 0M403 0M397
0I'4166 (~Id210
o
i~
2o
3o
~o
~t
so
~
7o
~-
~ ~
~
~o Days
Fig. 1. Diagram showing age at closure and duration of closure for the animals in this study. Stars indicate two animals described previously (Headon et al.'~).
been calculated f r o m these for each lamina. Comparisons between corresponding deprived, undeprived and normal laminae have been made using Student's t-test. Qualitative examination o f the L G N in all animals shows a marked difference between deprived and undeprived laminae, with cells in deprived laminae b e i n g smaller and paler than those in the undeprived laminae. Quantitative c o m p a r i s o n o f cell areas in corresponding deprived and undeprived laminae on opposite sides shows the deprived laminae to be approximately 20 % smaller than the undeprived laminae after 3-4 weeks o f closure (Table I, last c o l u m n ; Fig. 2A); this confirms previous findings in the monkey1,9,11,1< However, if the sizes o f cells in the undeprived and deprived laminae are c o m p a r e d to those in the corresponding laminae o f n o r m a l animals, it is clear that for the parvocetlular laminae most o f this difference in the first 6 weeks is due t o h y p e r t r o p h y o f cells in the undeprived laminae. This hypertrophy is
TABLE I
Mean cell areas ( + S.D.) for five animals following monocular closure from the first or second day o f life until 11 to 41 days Undeprived .
1 II II1 IV V VI
.
.
.
319.4 310.1 235.3 227.1 226.0 219.0
.
.
.
Deprived .
.
:r: 21.4 :z 34.0 m 19.9 ± 9.8 4- 20.4 ± 21.6
.
.
.
.
.
.
.
.
.
-~-8.4%* +6.7%n.s. +20.1%*** +18.4%*** +20.1%*** +20.6~***
.
.
.
.
.
.
.
.
.
.
263.1 258.8 187.2 186.3 172.0 172.0
.
.
Deprived vs undeprived .
.
.
m 28.1 ! 30.5 ~: 13.8 t 6.5 ± 12.3 ± 18.5
.
.
.
.
.
.
.
.
.
--10.7%* --11.0%* --4.5%n,s. 2.9% n . s . --8.6%* --5.3~ n.s.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
t7,6%** 16.5%* ---20.4,0/0** --18.0%*** --23.9%*** 21.5~**
* Significant, P < 0.05. ** Significant. P < 0.01. *** Significant, P < 0.001. Percentage differences and significances for the undeprived and deprived columns are for differences from normal animals (Headon et al.4).
441
~-
o •,
g
;,
......
MagnoceLtutar . Parvoce(lu[ar
~
-20k
-30f
~
*/, 30
•.... o. . . .
• Undeprivedmagnocetluiar o Deprivedmog~ocellu[ar
o.
o Deprived
Ur~emved porvocellular 20
~
~o
/
/
,.
./
~
"",
o -10 ~ ~>
-5(
~'~
porvocettutar
-~ .....
' ~ ' ~ u___-o
I,0
2,0 ~- 30
40
~---, 50 60
7;
8,0
90,
J 100
,~
, 400
j 410 Days
Fig. 2. A : graph showing m e a n shrinkage of cells in the deprived magno- and parvocellularlaminae in
meansize
in
relation to corresponding undeprived laminae against age at perfusion for animals with monocular lid suture performed in the first few days of life. B: graph showing the changes for cells undeprived and deprived, magno- and parvocellular laminae in relation to the mean cell size for the corresponding laminae o f normal animals for the same animals
asA.
highly significant for all the parvocellular laminae whereas the minor degree of shrinkage of the deprived parvocellular laminae only reaches significance in lamina V (Table 1, Fig. 2B). In the magnocellular laminae the results are less clearcut with evidence of both a small degree of hypertrophy of the undeprived laminae and shrinkage of the deprived. By 3 months of age the hypertrophy of the undeprived parvocellular cells has reversed but the difference between deprived and undeprived laminae is maintained almost constant because the deprived parvocellular laminae now shrink in parallel with the late shrinkage of the undeprived laminae. Ultimately the undeprived parvo-
442 TABLE 11 Mean cell areas ~ x S . D . j j b r two animals following long-term monocular closure#ore the first lew days o f rite
1 II III IV V VI
Undeprived
Deprived
327.6 ~_ 20.6 ~ 11.2~ ~" 313.1 rr: 9.9 ~7.7~* 178.8 T 1.8 8.8~*** 175.8 ~- 16.5 8.3% n.s. 172.2-z 1 0 . 2 8.5~n.s. 162.1 • 7.6 10.7%**
243.2 t 242.0 ~ 127.8 ~ 130.91 121.7 T 11t.0~
Deprived va umleprived
24.3 19.7 11.8 tl.5 1.1 18.7
17.4%** --16.8°,/o** ~--34.8~*** - 31.8~*** --353*** 38.9***
25.8 "'*'~'~,,, --22.7%*** 28.5~';.*** 25.5%*** --29.3%*** ~1.5%***
* Significant, P ~. 0.05. ** Significant, P .-_-0.01. *** Significant, P < 0.001. Percentage differences and significances for the undeprived and deprived columns are for difference from normal ammals (Headon et al.41. § Significance levels in this column are based on the conventional analysis using a comparison of sides within each animal and the standard deviations of the 50 cells in each sample are used. Both animals separately achieved the significance level shown for each lamina cellular l a m i n a e are a p p r o x i m a t e l y 10 ~ smaller than n o r m a l and the deprived parvocellular l a m i n a e a b o u t 35 % smaller (Table 1I). In contrast, the u n d e p r i v e d m ag n o cel lular l a m i n a e after long-term closure are a little larger than n o r m a l laminae: this is p r o b a b l y a reflection o f the small degree o f continued growth seen in these l a m i n a e in n o r m a l an i m a ls 4. These differences in b e h a v i o r o f cells in the m a g n o - and parvocelI ular l a m i n a e are c o n f i r m e d by the c h a n g e s in the ratio o f m e a n m a g n o c e l t u l a r cell area to m e a n p arv o c e l lu la r cell area with increasing d u r a t i o n o f closure, the ratios o f the 5 an i m al s at up to 6 weeks survival being significantly lower t h a n n o r m a l for the u n d e p r i v e d l a m i n a e mainly because o f the increase in size o f p ar v o cel l u l ar cells an d those o f the two l o n g - t e r m animals are significantly higher t h a n n o r m a l (Table III) because o f b o t h p a r v o c e l l u l a r shrinkage a n d m a g n o c e l l u l a r growth. Th e finding in this study o f a p p r o x i m a t e l y 25 % difference in size between the cells o f c o r r e s p o n d i n g deprived a n d u n d e p r i v e d l am i n ae o f the L G N af t er m o n o c u l a r TABLE lI1 Ratio o f mean magnocellular to parvocellular cell area r 7- S . D . )
Normal (n ~ 32) value -- 1.549 ± 0.176.
Early closurefor < 6 weeks (n :- 5) Early closure, tong survival (n - 2~
Undepri ved
Deprived
1.389 ± 0.042*** 1.860 .T. 0.056***
1.452 ~ 0.085 n.s. 1.983 Z= 0.184"*
** Significant P < 0.01. *** Significant P < 0.001. Significances are for differences from normal animals (Headon et al.4).
443 eyelid closure is in complete accord with earlier studies 1,9,11,12. This difference in size has previously been ascribed to shrinkage of the cells in the deprived laminae, but the major conclusion that can be made fi'om the present comparison of the deprived and undeprived laminae of the experimental animals with those of normal brains is that during the first 4-6 weeks after eyelid closure the difference for the parvocellular laminae at least is due to hypertrophy of the undeprived cells rather than shrinkage of the deprived ; shrinkage starts only after 4-6 weeks of closure and affects cells of both the deprived and undeprived laminae almost equally. There are now a number of findings which suggest that the primate visual system goes through at least two phases of postnatal developmental sensitivity. During the first 4-6 weeks of life cortical ocular dominance columns become established and during this period monocular visual deprivation causes major changes in the width of these columns and the balance of influence of the two eyes on the cortex 9. Following monocular closure from birth the difJerence in cell size between deprived and undeprived laminae reaches its maximum by 4 6 weeks of age. Both the plasticity of the ocular dominance columns and the ability of monocular closure to produce differences between deprived and undeprived laminae are greatly reduced with later closures up to 6 weeks of age 9,11,1~. Since after 3-6 weeks of monocular closure the axons of relay cells in the undeprived laminae of the LGN are supplying abnormally wide ocular dominance columns in the visual cortex, the finding that these cells have hypertrophied is perhaps not surprising and is consistent with the idea that the size of a cell soma is a reflection of the size of its axon and terminal arborization. However, although the ocular dominance bands receiving fi'om the deprived laminae are abnormally narrow there is no clear evidence of cell shrinkage, at least before 4 weeks of age. This may simply be that hypertrophy of a cell is intrinsically a faster process than shrinkage but it may also be an indication that the mechanisms by which cell size is controlled change at about 4-6 weeks of age. We have previously shown that late closure of an eye produces an approximately equal shrinkage of both deprived and undeprived parvocellular cells and have suggested that this results from interference with the establishment of normal cortical binocularity and represents a second phase of developmental sensitivity3, 5. The delayed shrinkage of both deprived and undeprived parvocellular cells seen here starting after 4-6 weeks of closure from birth is similar in a number of respects to the shrinkage produced by late closure in that it affects predominantly the parvoceIlular laminae, it affects deprived and undeprived cells approximately equally and is c f the same order of magnitude in both cases. It differs in that the peak of sensitivity to late closure is not until 6--9 months of age, whereas marked shrinkage of both deprived and undeprived palvocellular laminae occurred between 4-6 weeks and 3 months in this study; this may, however, be lzecause the same mechanism is acting on an already abnormal visual system following early closure. These results must also raise questions regarding the concept that these transneuronal changes are a degeneration or atrophy since at least up to 4 weeks the ~degenerate' ceils show no significant change in size from normal and the striking differences between deprived and undeprived laminae are due largely at least to
444
changes in undeprived cells. Following late closure, when both deprived and undeprived cells may have shrunk by 25 ~ , no obvious effect on visual function has been described although this clearly merits further study. There have been no reports of cell death in the LGN following monocular closure. It would perhaps be more useful to regard these changes in cell size produced by visual deprivation as being part of a process of adjustment of cells and their metabolism to the functional demands placed upon them and it may well be that such changes are much more widespread than has been hitherto supposed.
1 Headon, M. P. and Poweli, T. P. S., Cellular changes in the lateral geniculate nucleus of infant monkeys after suture of the eyelids, J. Anat. fLond.j, I 16 (1973) 135-145. 2 Headon, M. P. and Powell, T. P. S., The effect of bilateral eye closure upon the lateral genicutate nucleus in infant monkeys, Brain Research, 143 (1978) 147-154. 3 Headon, M. P., Sloper, J. J., Hiorns, R. W. and Powelt, T. P. S., Cell size changes in undeprived laminae of monkey lateral geniculate nucleus after monocular closure, Nature (Lond.), 281 (I979) 572-574. 4 Headon, M. P., Sloper, J. J., Hiorns, R. W. and Powdl, T. P. S., Cell sizes in thelateral geniculate nucleus of normal infant and adult Rhesus monkeys, Brain Research, 229 0981) 183-186. 5 Headon, M. P., Sloper, J. J., Hiorns, R. W. and Powell, T. P. S., Shrinkage of cells in undeprived laminae of the monkey lateral geniculate nucleus following late closure of one eye, Brain Research, 229 (1981) 187-192. 6 Hickey, T. L., Development of the dorsal lateral geniculate nucleus in normal and visually deprived cats, J. comp. Neurol., 189 (1980) 467-481. 7 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. 8 Kalil, R., A quantitative study of the effects of monocular ¢nucleation and deprivation on cell growth in the dorsal lateral geniculate nucleus of the cat, J. comp. Neurol., 189 0980) 483-524. 9 Le Vay, S., Wiescl. T. N. and Hubel, D. H., The development of ocular dominance columns in normal and visually deprived monkeys, J. comp. NeuroL, 191 0980) 1-51. 10 Sherman, S. M. and Wilson, J. R., Behavioral and morphological evidence for binocular competition in the postnatal development of the dog's visual system, J. comp. NeuroL, 161 (1975) 183-196. I 1 VitaI-Durand, F.. Garey, L. J. and Blakemore, C.. Monocular and binocular deprivation in the monkey: morphological effects and reversibility, Brain Research, 158 (1978) 45-64. 12 Von Noorden, G. K., Histological studies of the visual system in monkeys with experimental amblyopla, Invest. Ophthal., 12 (1973) 727-738.
Brain Research, 238 (1982) 439-444 Elsevier Biomedical Press
Initial hypertrophy of cells in undeprived laminae of the lateral genieulate nucleus of the monkey following early monocular visual deprivation
M. P. HEADON, J. J. SLOPER and T. P. S. POWELL Department of Human Anatomy, South Parks Road, Oxford OX1 3QX (U.K.)
(Accepted January 7th, 1982) Key words: lateral geniculate nucleus -- monkey
earlyeye closure - - hypertrophy
Comparisons of mean cell area in the lateral geniculate nucleus between normal and monocularly deprived Rhesus monkeysshow that closure started in the first few days of life produces an initial hypertrophy of up to 25 ~ affecting undeprived parvocellular cells. Hypertrophy is maximal at 4 weeks. Following this there is a later shrinkage affecting both deprived and undeprived parvocellular cells so that ultimately undeprived parvocellular cells are about 10~ smaller and deprived parvocellular cells about 35 ~,, smaller than corresponding cells in normal animals. Most studies of the effect of monocular visual deprivation on the lateral geniculate nucleus (LGN) have compared the sizes of cells in the deprived LGN laminae with those of cells in the corresponding undeprived laminae of the opposite nucleus and, although limitations of this approach have been recognized, it has generally been assumed that the predominant change resulting from visual deprivation is shrinkage or 'degeneration' of cells in the deprived laminae. Comparisons with normal animals have provided some evidence for an additional degree of hypertrophy of undeprived LGN cells in the cat 7 and dog 1° but this has not been found in other studies 6,s. Late closure of an eye in the monkey has recently been found to produce marked shrinkage of cells in undeprived L G N laminae when comparisons are made between experimental and normal monkeysZ 5; this has prompted a re-examination of the changes in LGN cell size produced by monocular closure performed in the first few days of life, making comparisons between deprived and undeprived cell sizes and cell sizes from normal animals. Measurements of cell area have been made for 50 cells in each lamina of 7 infant monkeys in which the lids over one eye had been sutured under open ether anesthesia in the first few days of life and the infants returned to their mothers for various survival periods (Fig. 1). Methods of perfusion, histological preparation and cell measurement are as described previously z. The normal cell sizes used as a control in this paper are taken from a previous paper a and are from both lateral geniculate nuclei of 16 normal rhesus monkeys prepared and measured using the same techniques as in this study. For statistical analysis the mean cell size for each lamina in each animal has been treated as a single observation and group mean and standard deviations have 0006-8993/82/0000-0000/$02.75 © Elsevier Biomedical Press
440
0M167 0M380 01,4399 0M403 0M397
0I'4166 (~Id210
o
i~
2o
3o
~o
~t
so
~
7o
~-
~ ~
~
~o Days
Fig. 1. Diagram showing age at closure and duration of closure for the animals in this study. Stars indicate two animals described previously (Headon et al.'~).
been calculated f r o m these for each lamina. Comparisons between corresponding deprived, undeprived and normal laminae have been made using Student's t-test. Qualitative examination o f the L G N in all animals shows a marked difference between deprived and undeprived laminae, with cells in deprived laminae b e i n g smaller and paler than those in the undeprived laminae. Quantitative c o m p a r i s o n o f cell areas in corresponding deprived and undeprived laminae on opposite sides shows the deprived laminae to be approximately 20 % smaller than the undeprived laminae after 3-4 weeks o f closure (Table I, last c o l u m n ; Fig. 2A); this confirms previous findings in the monkey1,9,11,1< However, if the sizes o f cells in the undeprived and deprived laminae are c o m p a r e d to those in the corresponding laminae o f n o r m a l animals, it is clear that for the parvocetlular laminae most o f this difference in the first 6 weeks is due t o h y p e r t r o p h y o f cells in the undeprived laminae. This hypertrophy is
TABLE I
Mean cell areas ( + S.D.) for five animals following monocular closure from the first or second day o f life until 11 to 41 days Undeprived .
1 II II1 IV V VI
.
.
.
319.4 310.1 235.3 227.1 226.0 219.0
.
.
.
Deprived .
.
:r: 21.4 :z 34.0 m 19.9 ± 9.8 4- 20.4 ± 21.6
.
.
.
.
.
.
.
.
.
-~-8.4%* +6.7%n.s. +20.1%*** +18.4%*** +20.1%*** +20.6~***
.
.
.
.
.
.
.
.
.
.
263.1 258.8 187.2 186.3 172.0 172.0
.
.
Deprived vs undeprived .
.
.
m 28.1 ! 30.5 ~: 13.8 t 6.5 ± 12.3 ± 18.5
.
.
.
.
.
.
.
.
.
--10.7%* --11.0%* --4.5%n,s. 2.9% n . s . --8.6%* --5.3~ n.s.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
.
t7,6%** 16.5%* ---20.4,0/0** --18.0%*** --23.9%*** 21.5~**
* Significant, P < 0.05. ** Significant. P < 0.01. *** Significant, P < 0.001. Percentage differences and significances for the undeprived and deprived columns are for differences from normal animals (Headon et al.4).
441
~-
o •,
g
;,
......
MagnoceLtutar . Parvoce(lu[ar
~
-20k
-30f
~
*/, 30
•.... o. . . .
• Undeprivedmagnocetluiar o Deprivedmog~ocellu[ar
o.
o Deprived
Ur~emved porvocellular 20
~
~o
/
/
,.
./
~
"",
o -10 ~ ~>
-5(
~'~
porvocettutar
-~ .....
' ~ ' ~ u___-o
I,0
2,0 ~- 30
40
~---, 50 60
7;
8,0
90,
J 100
,~
, 400
j 410 Days
Fig. 2. A : graph showing m e a n shrinkage of cells in the deprived magno- and parvocellularlaminae in
meansize
in
relation to corresponding undeprived laminae against age at perfusion for animals with monocular lid suture performed in the first few days of life. B: graph showing the changes for cells undeprived and deprived, magno- and parvocellular laminae in relation to the mean cell size for the corresponding laminae o f normal animals for the same animals
asA.
highly significant for all the parvocellular laminae whereas the minor degree of shrinkage of the deprived parvocellular laminae only reaches significance in lamina V (Table 1, Fig. 2B). In the magnocellular laminae the results are less clearcut with evidence of both a small degree of hypertrophy of the undeprived laminae and shrinkage of the deprived. By 3 months of age the hypertrophy of the undeprived parvocellular cells has reversed but the difference between deprived and undeprived laminae is maintained almost constant because the deprived parvocellular laminae now shrink in parallel with the late shrinkage of the undeprived laminae. Ultimately the undeprived parvo-
442 TABLE 11 Mean cell areas ~ x S . D . j j b r two animals following long-term monocular closure#ore the first lew days o f rite
1 II III IV V VI
Undeprived
Deprived
327.6 ~_ 20.6 ~ 11.2~ ~" 313.1 rr: 9.9 ~7.7~* 178.8 T 1.8 8.8~*** 175.8 ~- 16.5 8.3% n.s. 172.2-z 1 0 . 2 8.5~n.s. 162.1 • 7.6 10.7%**
243.2 t 242.0 ~ 127.8 ~ 130.91 121.7 T 11t.0~
Deprived va umleprived
24.3 19.7 11.8 tl.5 1.1 18.7
17.4%** --16.8°,/o** ~--34.8~*** - 31.8~*** --353*** 38.9***
25.8 "'*'~'~,,, --22.7%*** 28.5~';.*** 25.5%*** --29.3%*** ~1.5%***
* Significant, P ~. 0.05. ** Significant, P .-_-0.01. *** Significant, P < 0.001. Percentage differences and significances for the undeprived and deprived columns are for difference from normal ammals (Headon et al.41. § Significance levels in this column are based on the conventional analysis using a comparison of sides within each animal and the standard deviations of the 50 cells in each sample are used. Both animals separately achieved the significance level shown for each lamina cellular l a m i n a e are a p p r o x i m a t e l y 10 ~ smaller than n o r m a l and the deprived parvocellular l a m i n a e a b o u t 35 % smaller (Table 1I). In contrast, the u n d e p r i v e d m ag n o cel lular l a m i n a e after long-term closure are a little larger than n o r m a l laminae: this is p r o b a b l y a reflection o f the small degree o f continued growth seen in these l a m i n a e in n o r m a l an i m a ls 4. These differences in b e h a v i o r o f cells in the m a g n o - and parvocelI ular l a m i n a e are c o n f i r m e d by the c h a n g e s in the ratio o f m e a n m a g n o c e l t u l a r cell area to m e a n p arv o c e l lu la r cell area with increasing d u r a t i o n o f closure, the ratios o f the 5 an i m al s at up to 6 weeks survival being significantly lower t h a n n o r m a l for the u n d e p r i v e d l a m i n a e mainly because o f the increase in size o f p ar v o cel l u l ar cells an d those o f the two l o n g - t e r m animals are significantly higher t h a n n o r m a l (Table III) because o f b o t h p a r v o c e l l u l a r shrinkage a n d m a g n o c e l l u l a r growth. Th e finding in this study o f a p p r o x i m a t e l y 25 % difference in size between the cells o f c o r r e s p o n d i n g deprived a n d u n d e p r i v e d l am i n ae o f the L G N af t er m o n o c u l a r TABLE lI1 Ratio o f mean magnocellular to parvocellular cell area r 7- S . D . )
Normal (n ~ 32) value -- 1.549 ± 0.176.
Early closurefor < 6 weeks (n :- 5) Early closure, tong survival (n - 2~
Undepri ved
Deprived
1.389 ± 0.042*** 1.860 .T. 0.056***
1.452 ~ 0.085 n.s. 1.983 Z= 0.184"*
** Significant P < 0.01. *** Significant P < 0.001. Significances are for differences from normal animals (Headon et al.4).
443 eyelid closure is in complete accord with earlier studies 1,9,11,12. This difference in size has previously been ascribed to shrinkage of the cells in the deprived laminae, but the major conclusion that can be made fi'om the present comparison of the deprived and undeprived laminae of the experimental animals with those of normal brains is that during the first 4-6 weeks after eyelid closure the difference for the parvocellular laminae at least is due to hypertrophy of the undeprived cells rather than shrinkage of the deprived ; shrinkage starts only after 4-6 weeks of closure and affects cells of both the deprived and undeprived laminae almost equally. There are now a number of findings which suggest that the primate visual system goes through at least two phases of postnatal developmental sensitivity. During the first 4-6 weeks of life cortical ocular dominance columns become established and during this period monocular visual deprivation causes major changes in the width of these columns and the balance of influence of the two eyes on the cortex 9. Following monocular closure from birth the difJerence in cell size between deprived and undeprived laminae reaches its maximum by 4 6 weeks of age. Both the plasticity of the ocular dominance columns and the ability of monocular closure to produce differences between deprived and undeprived laminae are greatly reduced with later closures up to 6 weeks of age 9,11,1~. Since after 3-6 weeks of monocular closure the axons of relay cells in the undeprived laminae of the LGN are supplying abnormally wide ocular dominance columns in the visual cortex, the finding that these cells have hypertrophied is perhaps not surprising and is consistent with the idea that the size of a cell soma is a reflection of the size of its axon and terminal arborization. However, although the ocular dominance bands receiving fi'om the deprived laminae are abnormally narrow there is no clear evidence of cell shrinkage, at least before 4 weeks of age. This may simply be that hypertrophy of a cell is intrinsically a faster process than shrinkage but it may also be an indication that the mechanisms by which cell size is controlled change at about 4-6 weeks of age. We have previously shown that late closure of an eye produces an approximately equal shrinkage of both deprived and undeprived parvocellular cells and have suggested that this results from interference with the establishment of normal cortical binocularity and represents a second phase of developmental sensitivity3, 5. The delayed shrinkage of both deprived and undeprived parvocellular cells seen here starting after 4-6 weeks of closure from birth is similar in a number of respects to the shrinkage produced by late closure in that it affects predominantly the parvoceIlular laminae, it affects deprived and undeprived cells approximately equally and is c f the same order of magnitude in both cases. It differs in that the peak of sensitivity to late closure is not until 6--9 months of age, whereas marked shrinkage of both deprived and undeprived palvocellular laminae occurred between 4-6 weeks and 3 months in this study; this may, however, be lzecause the same mechanism is acting on an already abnormal visual system following early closure. These results must also raise questions regarding the concept that these transneuronal changes are a degeneration or atrophy since at least up to 4 weeks the ~degenerate' ceils show no significant change in size from normal and the striking differences between deprived and undeprived laminae are due largely at least to
444
changes in undeprived cells. Following late closure, when both deprived and undeprived cells may have shrunk by 25 ~ , no obvious effect on visual function has been described although this clearly merits further study. There have been no reports of cell death in the LGN following monocular closure. It would perhaps be more useful to regard these changes in cell size produced by visual deprivation as being part of a process of adjustment of cells and their metabolism to the functional demands placed upon them and it may well be that such changes are much more widespread than has been hitherto supposed.
1 Headon, M. P. and Poweli, T. P. S., Cellular changes in the lateral geniculate nucleus of infant monkeys after suture of the eyelids, J. Anat. fLond.j, I 16 (1973) 135-145. 2 Headon, M. P. and Powell, T. P. S., The effect of bilateral eye closure upon the lateral genicutate nucleus in infant monkeys, Brain Research, 143 (1978) 147-154. 3 Headon, M. P., Sloper, J. J., Hiorns, R. W. and Powelt, T. P. S., Cell size changes in undeprived laminae of monkey lateral geniculate nucleus after monocular closure, Nature (Lond.), 281 (I979) 572-574. 4 Headon, M. P., Sloper, J. J., Hiorns, R. W. and Powdl, T. P. S., Cell sizes in thelateral geniculate nucleus of normal infant and adult Rhesus monkeys, Brain Research, 229 0981) 183-186. 5 Headon, M. P., Sloper, J. J., Hiorns, R. W. and Powell, T. P. S., Shrinkage of cells in undeprived laminae of the monkey lateral geniculate nucleus following late closure of one eye, Brain Research, 229 (1981) 187-192. 6 Hickey, T. L., Development of the dorsal lateral geniculate nucleus in normal and visually deprived cats, J. comp. Neurol., 189 (1980) 467-481. 7 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. 8 Kalil, R., A quantitative study of the effects of monocular ¢nucleation and deprivation on cell growth in the dorsal lateral geniculate nucleus of the cat, J. comp. Neurol., 189 0980) 483-524. 9 Le Vay, S., Wiescl. T. N. and Hubel, D. H., The development of ocular dominance columns in normal and visually deprived monkeys, J. comp. NeuroL, 191 0980) 1-51. 10 Sherman, S. M. and Wilson, J. R., Behavioral and morphological evidence for binocular competition in the postnatal development of the dog's visual system, J. comp. NeuroL, 161 (1975) 183-196. I 1 VitaI-Durand, F.. Garey, L. J. and Blakemore, C.. Monocular and binocular deprivation in the monkey: morphological effects and reversibility, Brain Research, 158 (1978) 45-64. 12 Von Noorden, G. K., Histological studies of the visual system in monkeys with experimental amblyopla, Invest. Ophthal., 12 (1973) 727-738.