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Post-critical period plasticity of callosal transfer to visual cortex cells of cats following early conditioning of monocular deprivation and late optic chiasm transection
Brain Research, 516 (1990) 84-90 Elsevier
84 BRES 15441
Post-critical period plasticity of callosal transfer to visual cortex cells of cats following early conditioning of monocular deprivation and late optic chiasm transection U. Yinon and A. Hammer Physiological Laboratory, Maurice and Gabriela Goldschleger Eye Research Institute, Tel-Aviv University Faculty of Medicine, Chaim Sheba Medical Center, Tel-Hashomer (Israel) (Accepted 10 October 1989)
Key words: Critical period; Callosal transfer; Monocular deprivation; Chiasm transection; Cat; Visual cortex cell; Ocular dominance We studied whether plasticity-induced callosal transfer exists after the critical period for sensitivity of visual cortex cells in kittens postnatally monocularly deprived and in which interocular competition was cancelled by chiasm transection during adulthood. Callosal transfer was studied acutely (n = 3 cats) and chronically (n = 7) following the chiasm transection (OCAMD). For comparison, adult cats in which chiasm transection only was performed (OCA) were also studied acutely (n = 3) and chronically (n = 9). The results were also compared to cats in which monocular deprivation and chiasm transection were simultaneously performed (OCKMD) during development (n = 6) and to normal control cats (n = 18). Unit recording was extracellularly carried out in visual cortex areas 17 and 18 and their boundary region, where the corpus callosum is represented. When no interocular competition was allowed between the non-deprived and the deprived eye via the thalamocortical direct visual pathways on cortical cells, such as in the OCKMD cats, the absolute majority of the cells were ipsilaterally driven, regardless of which hemisphere was studied. Only a minor proportion (4.1%) of the cells had some contralateral input from the non-deprived eye in the hemisphere ipsilateral to the deprived eye, indicating almost no interhemispheric callosal transfer. A slight increase in the proportion of cells callosally driven from the non-deprived eye (9.8%), was found in this hemisphere in cats in which interocular competition was allowed via the direct visual pathways prior to its cancellation by chiasm transection (OCAMD), if studied acutely after the chiasm transection. A remarkable increase in callosal transfer was found in this hemisphere under chronic conditions. The proportions of these cells were 32.9% and 38.2% in the medium (3 weeks-3 months) and in the long chronic (6-22 months) groups of OCAMD cats, respectively. When no monocular deprivation, and hence interocular competition, was involved, such as in the OCA acute cats, a negligible proportion of cells (none in the left hemisphere and 5.1% in the right one), were callosally driven. A similar proportion of callosally driven cells were found in the OCA cats with medium (3 weeks-l.5 months; left hemisphere: 1.4%, right: 4.8%) and slightly more (left: 11.2%, right: 9.3%) in the cats with the longest postoperative period (6.5-32 months). Consistently, no cell with callosal input was found in the hemisphere contralateral to the deprived eye in the OCAMD cats while such cells, albeit few, were found in all OCA subgroups. It was concluded that preconditioning of cortical cells by monocular deprivation induces and facilitates the interhemispheric transfer of the resulting interocular competition. The non-deprived eye input governs that callosal transfer, occupying cortical cells in the 'inexperienced' hemisphere. However, for the cailosal transfer of the interocular competition to take place, by and large, the presence of the whole complement of the thalamocortical visual pathways is needed, at least for a certain limited period. If this condition is fulfilled, then the callosal transfer can be remarkably enhanced, even in the adult cat, after the termination of the plasticity period, providing a sufficiently long interval (following the chiasm transection) is given for recovery. INTRODUCTION The physiological consequences of monocular deprivation in cats have already been investigated extensively. The period of susceptibility (critical period) to the effect of monocular deprivation for visual cortex cells has been shown to begin at approx. 1 w e e k postnatally and to continue until nearly 4 months of age 2'3'1°'17A9. This time range also applies to the recovery of these cells from the effect of monocular deprivation. More recent results showed that this period extends to the 6th postnatal month6; no effect, however, of monocular deprivation was found on cortical cells in adult cats, even after long periods of exposure 1°'26.
The above-described effect of m o n o c u l a r deprivation depends on interocular competition b e t w e e n the visual inputs on synapses of cortical cells4'7A3'25'29. This competition is expected to resume when all cortical cells are occupied by the afferents of the non-deprived eye at the end of the susceptibility period. In contrast, evidence has been given that the interocular competition is an active neural process, existing also in the adult animal, providing monocular deprivation was developmentally initiated. It was found that cats monocularly deprived during development and having had a reverse eye closure for a long period during adulthood, showed a remarkable behavioral recovery of the deprived pathway 24. This is in keeping with physiological findings showing that removal
Correspondence: U. Yinon, Physiological Laboratory, Maurice and Grabriela Goldschleger Eye Research Institute, Tel-Aviv University Faculty of Medicine, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel. 0006-8993/90/$03.50 © 1990 Elsevier Science Publishers B.V. (Biomedical Division)
85 of the n o r m a l eye in adult, early monocularly deprived cats u n m a s k connections from the d e p r i v e d eye onto neurons in the visual cortex, thus allowing reinnervation of vacant synaptic sites by this eye 8'14'22. Thus, it is assumed that m o n o c u l a r occlusion p r o d u c e s a tonic inhibitory imbalance, which ultimately results in suppression of the response to stimulation of the deprived eye after the critical p e r i o d ; this inhibition is r e m o v e d when the n o n - d e p r i v e d eye is enucleated during adulthood. Thus, the latter authors suggest that plasticity is an active process, part of which continues also in the m a t u r e d brain. Elimination of the direct thalamocortical contralateral p a t h w a y s following split chiasm was p r o v e d to almost c o m p l e t e l y 16'33'34 or partially 1'15 abolish interocular interaction and hence c o m p e t i t i o n b e t w e e n the eyes. Thus, in view of the formerly described results 8'14'22, it is e x p e c t e d that in the adult split chiasm cats after develo p m e n t a l l y induced m o n o c u l a r deprivation, the deprived eye will be r e l e a s e d from the inhibitory influence of the n o r m a l eye. T h e e x p e c t e d p o s t o p e r a t i v e i m p r o v e m e n t of the response of the d e p r i v e d eye in these animals can indicate the a m o u n t of plasticity which has r e m a i n e d during adulthood. This e x p e r i m e n t a l m o d e l m a d e it also possible to study w h e t h e r the postcritical p e r i o d plasticity plays a role in the callosal transfer of the interocular c o m p e t i t i o n effect. W e present new evidence that a residual postcritical p e r i o d plasticity exists, providing the cortex has been
p r e c o n d i t i o n e d during the susceptibility p e r i o d to an e n v i r o n m e n t a l visual stress. MATERIALS AND METHODS We studied 4 major groups of cats (Table I): (1) Experimental cats (n = 10) which were postnatally monocularly deprived and in which interocular interaction was prevented after, or nearly at, the commencement of adulthood, by transection of the contralateral pathways in the optic chiasm. In this way long intervals were allowed between the operations for monocular deprivation and chiasm transection. These cats were studied electrophysiologically either acutely (OCAMD-A) or chronically at medium (OCAMDM) or long (OCAMD-L) postoperative intervals after the chiasm transection. Thus, in these cats all the chiasm operations and the electrophysiological studies were performed beyond the plasticity period for visual cortex development in cats, at an age when the cortex was physiologically mature TM. (2) A control group of cats (n = 12) operated during adulthood for chiasm transection and electrophysiologicallystudied acutely (OCA-A) and at chronically medium (OCA-M) and long (OCA-L) postoperative intervals, according to a similar timetable to the various OCAMD subgroups. (3) A control group of cats (n = 6) operated during development simultaneously for monocular deprivation and chiasm transection (OCKMD). In these cats, therefore, no time interval was allowed between the monocular deprivation and the chiasm transection. These cats were chronically electrophysiologically studied long periods after the chiasm transection. (4) Normal control cats (n = 18). The optic chiasm operation was made in the transbuccal approach18'33. Unit recording was extraceilularly carried out mainly in the boundary region between areas 17 and 18, where the callosal zone and the vertical meridian are represented9'11. Our recording sites in this region were morphologically selected2° and histologically confirmed. The spatial representation of the vertical meridian was optically determined and was found to be similar to the calculated value23. Histological examinations were carried out on
TABLE I The experimental cats operated during development for monocular deprivation and during adulthood for chiasm transection (OCAMD) and the control groups of adult transected (OCA) cats and cats operated simultaneously for monocular deprivation and chiasm transection (OCKMD) and normal cats
MD, monocular deprivation; time is given in total range. Group of cats
No. of cats
Age at MD operation Age at chiasm operation
Postoperative time
OCAMD-A Acute OCAMD-M Medium chronic OCAMD-L long chronic
3
1 week-2 weeks
8 months-12 months, I week
0 week- 1 week
4
1 week-3 weeks
6 months, 1 week-14 months, 2 weeks
3 weeks-2 months, 3 weeks
3
2 weeks-4 weeks
8 months, 1 week-10 months, 3 weeks
5 months, 3 weeks-22 months
OCA-A Acute OCA-M Medium chronic OCA-L long chronic
3
Unknown (adult) Unknown (adult)
0 week-1 week
Unknown (adult)
6 months, 2 weeks-32 months
6 weeks
4 months, 1 week-16 months, 1 week
OCKMD Normal controls
5 4
6 18
6 weeks
3 weeks-1 month, 2 weeks
86
the eyes, the chiasm and the visual cortex 12 after the physiological experiments; sections of the eyes were stained with Hematoxylin/ Eosin. The chiasm surgical transection was found to be complete in all operated cats presently studied, as inferred from their histological cross-sections and the absence of ganglion cells from the nasal retinae of both eyes. All other details regarding the anesthesia, surgery, postoperative maintenance, electrophysiology, stimulation and data analysis were as previously described 3°'33.
found in these cats thus reflects a transfer of input via the corpus callosum. The ipsilateral eye response in the two hemispheres was almost equal in the O C A - A (acute) cats; as to the contralateral (callosal) response, it was reflected in 5.1% of the cells in the right hemisphere of these cats (Fig. 2B). A remarkable difference, however, was found between the two hemispheres of the O C A M D - A (acute) cats with regard to the ipsilateral response. While in the hemisphere ipsilaterally to the deprived eye of these cats 25.5% of the cells were monocularly ipsilaterally driven, their proportion in the contralateral hemisphere was 57.1%. As for contralateral eye input, it was found in 9.8% of the binocular and monocular cells in the hemisphere ipsilateral to the deprived e y e , while no such cells were found in the contralateral hemisphere. This means an invasion of visual input from the hemisphere ipsilateral to the non-deprived eye to the fellow hemisphere via the corpus callosum. H o w e v e r , it is important to note here that in two of the O C A M D - A cats in which no recovery time was allowed after the chiasm transection, no such an invasion of callosal input was found. Callosally driven cells were found only in one animal of
RESULTS The distribution of the cortical cells according to their ocular dominance shows that in the acutely operated cats, whether early monocularly deprived ( O C A M D - A ) or not ( O C A - A ) , the cells activated via the ipsilateral eye constituted the majority of the responsive cells (Figs. 1, 2). This dominance of the ipsilateral eye is very prominent in comparison to the small minority of ipsilaterally driven cells in the normal control cats (Fig. 3). While the ipsilateral eye dominance in the chiasm-transected cats reflects the visual input of the direct intact connectivity, the minor response originating from the other eye is an indication of the absence of the direct contralateral pathways in these cats. The same contralateral response
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Fig. 1. Histograms showing the ocular dominance distribution of cortical cells in the visual cortex (areas 17, 18 and their boundary region) in the experimental OCAMD cats. Data are presented separately for the acute (Acute, A,B), medium chronic (M. chronic, C,D), and long chronic (L. chronic, E,F) cats according to the postoperative interval after the chiasm transection. Histograms A,C,E and B,D,F of these cats represent the responses in the hemisphere ipsilateral and contralateral to the deprived eye, respectively. The percentage distribution of cells is calculated separately for each ocular dominance group. The name of each group of cats and the side of hemisphere from which unit recording was performed with regard to the deprived eye, is indicated above the upper left corner of each histogram (CONTRA, contralateral; IPSI, ipsilateral). The number of cells studied in each hemisphere and the number of cats in each group are indicated above the right corner. Ocular dominance groups C and C>I represent cells driven either monocularly or binocularly with contralateral eye dominance, respectively; groups I and C
87 this group in which a recovery time of 1 week was given. It is interesting to note here that the results of the O C A M D - A cats are similar to those of the O C K M D cats in which monocular deprivation and chiasm transection were simultaneously performed, thus permitting no time interval between them. Firstly, most of the visually active cells in both groups of cats were ipsilaterally driven. Secondly, cells with callosal input (4.1%) were found in the hemisphere ipsilateral to the deprived eye of the O C K M D cats and practically none (0.8%) in the contralateral hemisphere, almost the same situation as in the O C A M D - A cats (Fig. 3A,B). Thirdly, there is similarity in the general hemispheric responsiveness level. In the hemisphere ipsilateral to the deprived eye of both O C A M D - A and O C K M D cats nearly 65% of the cells were visually unresponsive, while in the contralateral hemisphere the proportion of these cells in both groups of cats was practically the same (nearly 40%). Different results were obtained for the chronic groups of the O C A M D cats, in which long periods of recovery had elapsed after the chiasm transection. During this period, and unlike in the previously described acute cats ( O C A M D - A ) , an opportunity was given to the visual input to freely propagate interhemispherically via the corpus caUosum. Indeed, such a propagation took place already in the medium chronic cats (OCAMD-M) as reflected in the remarkable increase in the proportion of callosally activated cells. These cells constituted 32.9% of all cells with contralateral eye input in the hemisphere ipsilateral to the deprived eye (Fig. 1C) in comparison to
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the analogous hemisphere of the acute cats O C A M D - A (9.8%; Fig. 1A). An even higher proportion of caUosally driven cells (38.2%) was found in this hemisphere in the long chronic group (OCAMD-L; Fig. 1E). No difference, however, was found between the chronic and the acute O C A M D subgroups with regard to the contralateral hemisphere; there were no cells in that hemisphere with callosal input (Fig. 1B,D,F). The results of the O C A M D subgroups show a clear tendency for an increase in the proportion of caUosally driven cells in the hemisphere ipsilateral to the deprived tF eye as function of recovery time (following the callosal transection). This change is accompanied by a concomitant reduction in the proportion of cells with ipsilateral eye input in this hemisphere. As to the contralateral hemisphere, there were no callosaUy driven cells there, but the proportion of ipsilaterally driven cells showed a consistent increase with recovery time. In comparison, in the analogous subgroups of O C A cats a consistent increase both in the callosally driven cells and in the ipsilaterally driven cells (Fig. 2 A - F ) as function of recovery time was found. Thus, the basic difference between the O C A M D and the O C A cats is the remarkable increase, in the former group, in the proportion of callosally driven cells in the ipsilateral hemisphere, at the expense of the evacuation of these cells from the fellow hemisphere. It is worth mentioning here the changes found in the various groups of operated and normal cats with regard to the general level of responsiveness of cortical neurons.
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While in the normal cats the proportion of the visually unresponsive cells was 11.2% (Fig. 3C), it was much higher in the experimental cats. It ranged between 64.7% in the hemisphere ipsilateral to the deprived eye of the OCAMD-A (Fig. 1A) and 58.8% in the OCAMD-L cats (Fig. 1E); in the contralateral hemisphere of these cats the results were 42.8% (Fig. 1B) and 22% (Fig. 1F), respectively. Similarly, in the analogous subgroup of OCA-A cats nearly 48% of the cells were visually unresponsive in both hemispheres (Fig. 2A,B) while in the OCA-L cats the proportions were 24.7% in one hemisphere and 35.2% in the other (Fig. 2E,F). Thus, there is a clear tendency for an increase in the responsiveness level with recovery time. DISCUSSION It is evident from the results of the present study that although interhemispheric callosal transfer of interocular competition exists, it is normally maintained at a low level. Our present study has proved that the following conditions have to be fulfilled in order to induce a massive callosal transfer. (1) A permanent imbalance has to be induced in the interocular competition mechanism. This condition can be created only during the developmental period by suppressing one visual input by monocular deprivation 4,7,]3,25'29. (2) A minimal period of competition must take place between the deprived and the normal inputs. During that period the callosal
transfer increases as function of time; if this condition, however, is not fulfilled, the transfer is maintained, albeit at a minor level. (3) The involvement of the thalamocortical pathways is essential, whether during normal development or at adulthood; the present experimental model applies to the contralateral pathways. In the absence of these pathways the callosal transfer is remarkably depleted or even completely eliminated. (4) A long recovery time is needed after the chiasm transection. This has been clearly reflected in the remarkable amount of callosal transfer found in our chronic cats in comparison to the acute cats. For normal callosal transfer to exist, the presence of the whole complement of geniculocortical pathways is needed as already previously proved by us in optic chiasm 33'34- and optic tract-transected cats 28'34. In the chiasm-transected animals only a minor amount of callosal transfer has been found by us as also presently confirmed (our recent study shows a greater transfer if chiasm transection was performed developmentally31). This condition is further emphasized by the fact that in our experimental model, the cat, the decussation is asymmetric 21 and thus the majority of the direct visual input was eliminated by the chiasm transection. That the corpus callosum is the only mediator of the small amount of interhemispheric transfer of visual information found in the above-described animals, has already been proved by us previously. We showed a complete absence of callosal transfer in split brain cats, i.e., when the corpus
89 callosum was eliminated in addition to the chiasm transection29,30,32 Presently we have proved that it is possible to induce an increase in the callosal transfer if the elimination of the contralateral pathways is combined with monocular deprivation (OCAMD). This caused rerouting of the visual input to cortical cells from the conventional geniculocortical to the callosal pathway. Under this condition unidirectional interhemispheric flow of visual information was forced, due to interocular competition between the normal and the deprived eye. The conventional interocular competition mediated via the thalamocortical pathways had thus turned to being an interhemispheric competition. The input from the normal eye that travelled via the remaining callosal pathway invaded the hemisphere ipsilateral to the deprived eye to regain synaptic sites there which were abandoned by afferents from the deprived eye. This was proved by the very remarkable fact that no cells with callosal input from the deprived eye were found in the hemisphere ipsilateral to the normal eye, in sharp contrast to the presence of many callosally driven cells in the fellow hemisphere. Callosally driven cells, albeit in small proportions, were usually found in both hemispheres of our late chiasm-operated and normally exposed cats (OCA). Our findings clearly indicate that only after a long interval following the onset of monocular deprivation, the hemisphere ipsilateral to the deprived eye had accepted the indirect callosal input, as a substitution for the blocked direct input. During this period the interocular competition via the direct pathways had established in the cortex an imbalance between the normal and the deprived eye's outputs. It was indeed proved by us that in the absence of such an interval in the OCKMD cats, and as a consequence of loss of conventional interocular competition, a negligible callosal transfer exists27'35. The callosal transfer was therefore rendered ineffective in these cats due to its dependency on the conventional interocular competition. This hypothesis is not supported by the results of previous investigators showing a considerable amount of callosal transfer under the same conditionsS; the latter investigators however, found also a remarkable transfer in chiasm-transected adult cats in contradiction to our results. REFERENCES 1 Berlucchi, G. and Rizzolatti, G., Binocularly driven neurons in visual cortex of split-chiasm cats, Science, 159 (1968) 308-310. 2 Berman, N. and Daw, N.W., Comparison of the critical periods for monocular and directional deprivation in cats, J. Physiol. (Lond.), 265 (1977) 249-259. 3 Blakemore, C. and Van Siuyters, R.C., Reversal of the physiologicaleffects of monocular deprivation in kittens. Further evidence for a sensitive period, J. Physiol. (Lond.), 237 (1974)
The cancellation of the contralateral pathways induces separation of the two hemispheres to a great extent; each hemisphere becoming governed by its own, ipsilateral eye33,34. This separation is also preserved if the above operation is developmentally carried out, whether in normal 31 or in monocularly deprived kittens 27'35. In the latter, the hemisphere ipsilateral to the non-deprived eye was proved to be the 'experienced' one, as reflected in the responsiveness level of the cells there, in comparison to the fellow hemisphere. In the OCAMD cats of the present study, this condition developed in the adult cats, at a certain recovery period after the transection of the optic chiasm. It was thus proved that once the situation of the 'experienced' and 'inexperienced' hemispheres was established, in accordance with the appropriate visual inputs, the callosal transfer was triggered. In the present study, therefore, both the hemispheric difference and the callosal transfer were induced after the termination of the plasticity period, providing preconditioning by monocular deprivation had taken place during development. As to the mechanism of the interocular competition we have new evidence from the present study that it is inhibitory. When monocular deprivation was performed at an early age (first postoperative month, as in our OCAMD cats), 3.3% of all cells were monocularly driven by the deprived eye 36. In contrast, in the OCAMD-A cats of the present study, the monocularly driven cells from the deprived eye constituted 25.5% of all cells in the hemisphere ipsilateral to the deprived eye. Thus, the release from inhibitory action of the normal eye (following sectioning of the contralateral pathways), enhanced the activity of the deprived eye. This is in keeping with similar results previously found following removal of the normal eye in early monocularly deprived adult cats 8'13'14'22. However, the interocular inhibition found by us is temporary; while in the acute cats (OCAMD-A) 25.5% of the cells were driven by the deprived eye, they constituted only 2.9% in the long chronic group (OCAMD-L). The latter result is already similar to the one obtained by us for monocularly deprived cats 36. Thus, while the postcritical period interocular inhibitory mechanism is temporary, the previously described postcritical callosal transfer is permanent and was enhanced with recovery time. 195-216. 4 Blakemore, C., Van Sluyters, R.C. and Movshon, J.A., Synaptic competition in the kitten's visual cortex. In Cold Spring Harbor Symposia on Quantitative Biology, Cold Spring Harbor Laboratory, New York, 1976, pp. 601-609. 5 Cynader, M., Lepore, E and Guillemot, J.P., Interhemispheric competition during postnatal development, Nature (Lond.), 290 (1981) 139-140. 6 Cynader, M., Timney, B.N. and Mitchell, D.E., Period of susceptibility of kitten visual cortex to the effects of monocular
90 deprivation extends beyond six months of age, Brain Research, 91 (1980) 545-550. 7 Guillery, R.W., Binocular competition in the control of geniculate cell growth, J. Comp. Neurol., 144 (1972) 117-130. 8 Hoffmann, K.-P. and Cynader, M., Functional aspects of plasticity in the visual system of adult cats after early monocular deprivation, Philosoph. Trans. R. Soc. Lond. B, 278 (1977) 411-424. 9 Hubel, D.H. and Wiesel, T.N., Cortical and callosal connections concerned with the vertical meridian of visual fields in the cat, J. Neurophysiol., 30 (1967) 1561-1573. 10 Hubel, D.H. and Wiesel, T.N., The period of susceptibility to the physiological effects of unilateral eye closure in kittens, J. Physiol. (Lond.), 206 (1970) 419-436. 11 Innocenti, G.M., The primary visual pathway through the corpus callosum: morphological and functional aspects in the cat, Arch. Ital. Biol., 118 (1980) 124-188. 12 Kluver, H. and Barrera, E., A method for the combined staining of cells and fibers in the nervous system, J. Neuropathol. Exp. Neurol., 12 (1953) 400-403. 13 Kratz, K.E. and Spear, ED., Effect of visual deprivation and alterations in binocular competition on responses of striate cortex neurons in the cat, J. Comp. Neurol., 170 (1976) 141-152. 14 Kratz, K.E., Spear, P.D. and Smith, D.C., Postcritical period reversal of effects of monocular deprivation on striate cortex cells in the cat, J. Neurophysiol., 39 (1976) 501-511. 15 Lepore, E and Guillemot, J.P., Visual receptive field properties of cells innervated through the corpus callosum in the cat, Exp. Brain Res., 46 (1982) 413-424. 16 Milleret, C. and Buser, P., Receptive field sizes and responsiveness to light in area 18 of the adult cat after chiasmotomy. Postoperative evolution; role of visual experience, Exp. Brain Res., 57 (1984) 73-81. 17 Movshon, J.A., Reversal of the physiological effects of monocular deprivation in the kitten's visual cortex, J. Physiol. (Lond.), 261 (1976) 125-174. 18 Myers, R.E., Interocular transfer of pattern discrimination in cats following section of crossed optic fibers, J. Comp. Physiol. Psychol., 48 (1955) 470-473. 19 OIson, C.R. and Freeman, R.D., Profile of the sensitive period for monocular deprivation in kittens, Exp. Brain Res., 39 (1980) 17-21. 20 Otsuka, R. and Hassler, R., Uber Aufbau und Gleidcrung der corticalen Sehsph~ire bei der Katze, Arch. Psychiatr. Zeitschr. Neurol., 203 (1962) 212-234. 21 Polyak, S., The Vertebrate Visual System, University of Chicago Press, Chicago, 1957. 22 Smith, D.C., Spear, P.D. and Kratz, K.E., Role of visual
experience in postcritical period reversal of effects of monocular deprivation in cat striate cortex, J. Comp. Neurol., 178 (1978) 313-328. 23 Vakkur, G.J., Bishop, P.O. and Kozak, W., Visual optics in the cat, including posterior nodal distance and retinal landmarks, Vision Res., 3 (1963) 289-314. 24 Van Hof-van Duin, J., Early and permanent effect of monocular deprivation on pattern discrimination and visuomotor behaviour in cats, Brain Research, 111 (1973) 261-276. 25 Wiesel, T.N. and Hubel, D.H., Comparison of the effects of unilateral and bilateral eye closure on cortical unit responses in kittens, J. Neurophysiol., 28 (1965) 1030-1040. 26 Yinon, U., On the question of neuronal plasticity in the mature visual cortex+ Arch. Ital. Biol., 116 (1978) 324-329. 27 Yinon, U., Hydrocephalus developed in cat: physiology of visual cortex cells, Clin. Vision Sci., 4 (1989) 79-84. 28 Yinon, U. and Achiron, A., Unilateral interruption of geniculate and callosal inputs to the visual cortex of cats: ocular dominance and responsiveness of cells in the deafferented and in the intact hemispheres, Exp. Neurol., 99 (1988) 579-588. 29 Yinon, U. and Chen, M., Visual split brain and monocular deprivation in kittens: differentiation between the effects of disuse and of binocular competition in visual cortex cells, Behav. Brain Res., 30 (1988) 273-278. 30 Yinon, U. and Chen, M., Split brain surgically performed in developing and in adult cats: physiological properties and recovery of visual cortex neurons. In H. Flohr (Ed.), Post-lesion Neural Plasticity, Springer-Verlag, Berlin, 1988, pp. 187-201. 31 Yinon, U., Chen, M. and Hammer, A., Split chiasm developmentally induced in kittens: plasticity of interhemispheric transfer in visual cortex cells, Exp. Brain Res., 72 (1988) 201-203. 32 Yinon, U., Chen, M. and Hammer, A., Midsagittal transection of the optic chiasm and the corpus callosum induces split brain in cats: the effect on ocular dominance and responsiveness of cells in the visual cortex, Exp. Neurol., 101 (1988) 107-113. 33 Yinon, U. and Hammer, A., Optic chiasm split and binocularity diminution in cortical cells of acute and of chronic operated adult cats, Exp. Brain Res., 58 (1985) 552-558. 34 Yinon, U., Hammer, A. and Podell, M., The hemispheric dominance of cortical cells in the absence of direct visual pathways, Brain Research, 232 (1982) 187-190. 35 Yinon, U., Hammer, A. and Weiser, Z.D., Split chiasm and monocular deprivation during development: a model of noncompetitive mechanism in visual cortex neurons, Soc. Neurosci. Abstr., 11 (1985) 462. 36 Yinon, U., Podell, M. and Goshen, S., Deafferentation of the visual cortex: the effect on cortical cells in normal and in early monocularly deprived cats, Exp. Neurol., 83 (1984) 486-494.
84 BRES 15441
Post-critical period plasticity of callosal transfer to visual cortex cells of cats following early conditioning of monocular deprivation and late optic chiasm transection U. Yinon and A. Hammer Physiological Laboratory, Maurice and Gabriela Goldschleger Eye Research Institute, Tel-Aviv University Faculty of Medicine, Chaim Sheba Medical Center, Tel-Hashomer (Israel) (Accepted 10 October 1989)
Key words: Critical period; Callosal transfer; Monocular deprivation; Chiasm transection; Cat; Visual cortex cell; Ocular dominance We studied whether plasticity-induced callosal transfer exists after the critical period for sensitivity of visual cortex cells in kittens postnatally monocularly deprived and in which interocular competition was cancelled by chiasm transection during adulthood. Callosal transfer was studied acutely (n = 3 cats) and chronically (n = 7) following the chiasm transection (OCAMD). For comparison, adult cats in which chiasm transection only was performed (OCA) were also studied acutely (n = 3) and chronically (n = 9). The results were also compared to cats in which monocular deprivation and chiasm transection were simultaneously performed (OCKMD) during development (n = 6) and to normal control cats (n = 18). Unit recording was extracellularly carried out in visual cortex areas 17 and 18 and their boundary region, where the corpus callosum is represented. When no interocular competition was allowed between the non-deprived and the deprived eye via the thalamocortical direct visual pathways on cortical cells, such as in the OCKMD cats, the absolute majority of the cells were ipsilaterally driven, regardless of which hemisphere was studied. Only a minor proportion (4.1%) of the cells had some contralateral input from the non-deprived eye in the hemisphere ipsilateral to the deprived eye, indicating almost no interhemispheric callosal transfer. A slight increase in the proportion of cells callosally driven from the non-deprived eye (9.8%), was found in this hemisphere in cats in which interocular competition was allowed via the direct visual pathways prior to its cancellation by chiasm transection (OCAMD), if studied acutely after the chiasm transection. A remarkable increase in callosal transfer was found in this hemisphere under chronic conditions. The proportions of these cells were 32.9% and 38.2% in the medium (3 weeks-3 months) and in the long chronic (6-22 months) groups of OCAMD cats, respectively. When no monocular deprivation, and hence interocular competition, was involved, such as in the OCA acute cats, a negligible proportion of cells (none in the left hemisphere and 5.1% in the right one), were callosally driven. A similar proportion of callosally driven cells were found in the OCA cats with medium (3 weeks-l.5 months; left hemisphere: 1.4%, right: 4.8%) and slightly more (left: 11.2%, right: 9.3%) in the cats with the longest postoperative period (6.5-32 months). Consistently, no cell with callosal input was found in the hemisphere contralateral to the deprived eye in the OCAMD cats while such cells, albeit few, were found in all OCA subgroups. It was concluded that preconditioning of cortical cells by monocular deprivation induces and facilitates the interhemispheric transfer of the resulting interocular competition. The non-deprived eye input governs that callosal transfer, occupying cortical cells in the 'inexperienced' hemisphere. However, for the cailosal transfer of the interocular competition to take place, by and large, the presence of the whole complement of the thalamocortical visual pathways is needed, at least for a certain limited period. If this condition is fulfilled, then the callosal transfer can be remarkably enhanced, even in the adult cat, after the termination of the plasticity period, providing a sufficiently long interval (following the chiasm transection) is given for recovery. INTRODUCTION The physiological consequences of monocular deprivation in cats have already been investigated extensively. The period of susceptibility (critical period) to the effect of monocular deprivation for visual cortex cells has been shown to begin at approx. 1 w e e k postnatally and to continue until nearly 4 months of age 2'3'1°'17A9. This time range also applies to the recovery of these cells from the effect of monocular deprivation. More recent results showed that this period extends to the 6th postnatal month6; no effect, however, of monocular deprivation was found on cortical cells in adult cats, even after long periods of exposure 1°'26.
The above-described effect of m o n o c u l a r deprivation depends on interocular competition b e t w e e n the visual inputs on synapses of cortical cells4'7A3'25'29. This competition is expected to resume when all cortical cells are occupied by the afferents of the non-deprived eye at the end of the susceptibility period. In contrast, evidence has been given that the interocular competition is an active neural process, existing also in the adult animal, providing monocular deprivation was developmentally initiated. It was found that cats monocularly deprived during development and having had a reverse eye closure for a long period during adulthood, showed a remarkable behavioral recovery of the deprived pathway 24. This is in keeping with physiological findings showing that removal
Correspondence: U. Yinon, Physiological Laboratory, Maurice and Grabriela Goldschleger Eye Research Institute, Tel-Aviv University Faculty of Medicine, Chaim Sheba Medical Center, Tel-Hashomer, 52621, Israel. 0006-8993/90/$03.50 © 1990 Elsevier Science Publishers B.V. (Biomedical Division)
85 of the n o r m a l eye in adult, early monocularly deprived cats u n m a s k connections from the d e p r i v e d eye onto neurons in the visual cortex, thus allowing reinnervation of vacant synaptic sites by this eye 8'14'22. Thus, it is assumed that m o n o c u l a r occlusion p r o d u c e s a tonic inhibitory imbalance, which ultimately results in suppression of the response to stimulation of the deprived eye after the critical p e r i o d ; this inhibition is r e m o v e d when the n o n - d e p r i v e d eye is enucleated during adulthood. Thus, the latter authors suggest that plasticity is an active process, part of which continues also in the m a t u r e d brain. Elimination of the direct thalamocortical contralateral p a t h w a y s following split chiasm was p r o v e d to almost c o m p l e t e l y 16'33'34 or partially 1'15 abolish interocular interaction and hence c o m p e t i t i o n b e t w e e n the eyes. Thus, in view of the formerly described results 8'14'22, it is e x p e c t e d that in the adult split chiasm cats after develo p m e n t a l l y induced m o n o c u l a r deprivation, the deprived eye will be r e l e a s e d from the inhibitory influence of the n o r m a l eye. T h e e x p e c t e d p o s t o p e r a t i v e i m p r o v e m e n t of the response of the d e p r i v e d eye in these animals can indicate the a m o u n t of plasticity which has r e m a i n e d during adulthood. This e x p e r i m e n t a l m o d e l m a d e it also possible to study w h e t h e r the postcritical p e r i o d plasticity plays a role in the callosal transfer of the interocular c o m p e t i t i o n effect. W e present new evidence that a residual postcritical p e r i o d plasticity exists, providing the cortex has been
p r e c o n d i t i o n e d during the susceptibility p e r i o d to an e n v i r o n m e n t a l visual stress. MATERIALS AND METHODS We studied 4 major groups of cats (Table I): (1) Experimental cats (n = 10) which were postnatally monocularly deprived and in which interocular interaction was prevented after, or nearly at, the commencement of adulthood, by transection of the contralateral pathways in the optic chiasm. In this way long intervals were allowed between the operations for monocular deprivation and chiasm transection. These cats were studied electrophysiologically either acutely (OCAMD-A) or chronically at medium (OCAMDM) or long (OCAMD-L) postoperative intervals after the chiasm transection. Thus, in these cats all the chiasm operations and the electrophysiological studies were performed beyond the plasticity period for visual cortex development in cats, at an age when the cortex was physiologically mature TM. (2) A control group of cats (n = 12) operated during adulthood for chiasm transection and electrophysiologicallystudied acutely (OCA-A) and at chronically medium (OCA-M) and long (OCA-L) postoperative intervals, according to a similar timetable to the various OCAMD subgroups. (3) A control group of cats (n = 6) operated during development simultaneously for monocular deprivation and chiasm transection (OCKMD). In these cats, therefore, no time interval was allowed between the monocular deprivation and the chiasm transection. These cats were chronically electrophysiologically studied long periods after the chiasm transection. (4) Normal control cats (n = 18). The optic chiasm operation was made in the transbuccal approach18'33. Unit recording was extraceilularly carried out mainly in the boundary region between areas 17 and 18, where the callosal zone and the vertical meridian are represented9'11. Our recording sites in this region were morphologically selected2° and histologically confirmed. The spatial representation of the vertical meridian was optically determined and was found to be similar to the calculated value23. Histological examinations were carried out on
TABLE I The experimental cats operated during development for monocular deprivation and during adulthood for chiasm transection (OCAMD) and the control groups of adult transected (OCA) cats and cats operated simultaneously for monocular deprivation and chiasm transection (OCKMD) and normal cats
MD, monocular deprivation; time is given in total range. Group of cats
No. of cats
Age at MD operation Age at chiasm operation
Postoperative time
OCAMD-A Acute OCAMD-M Medium chronic OCAMD-L long chronic
3
1 week-2 weeks
8 months-12 months, I week
0 week- 1 week
4
1 week-3 weeks
6 months, 1 week-14 months, 2 weeks
3 weeks-2 months, 3 weeks
3
2 weeks-4 weeks
8 months, 1 week-10 months, 3 weeks
5 months, 3 weeks-22 months
OCA-A Acute OCA-M Medium chronic OCA-L long chronic
3
Unknown (adult) Unknown (adult)
0 week-1 week
Unknown (adult)
6 months, 2 weeks-32 months
6 weeks
4 months, 1 week-16 months, 1 week
OCKMD Normal controls
5 4
6 18
6 weeks
3 weeks-1 month, 2 weeks
86
the eyes, the chiasm and the visual cortex 12 after the physiological experiments; sections of the eyes were stained with Hematoxylin/ Eosin. The chiasm surgical transection was found to be complete in all operated cats presently studied, as inferred from their histological cross-sections and the absence of ganglion cells from the nasal retinae of both eyes. All other details regarding the anesthesia, surgery, postoperative maintenance, electrophysiology, stimulation and data analysis were as previously described 3°'33.
found in these cats thus reflects a transfer of input via the corpus callosum. The ipsilateral eye response in the two hemispheres was almost equal in the O C A - A (acute) cats; as to the contralateral (callosal) response, it was reflected in 5.1% of the cells in the right hemisphere of these cats (Fig. 2B). A remarkable difference, however, was found between the two hemispheres of the O C A M D - A (acute) cats with regard to the ipsilateral response. While in the hemisphere ipsilaterally to the deprived eye of these cats 25.5% of the cells were monocularly ipsilaterally driven, their proportion in the contralateral hemisphere was 57.1%. As for contralateral eye input, it was found in 9.8% of the binocular and monocular cells in the hemisphere ipsilateral to the deprived e y e , while no such cells were found in the contralateral hemisphere. This means an invasion of visual input from the hemisphere ipsilateral to the non-deprived eye to the fellow hemisphere via the corpus callosum. H o w e v e r , it is important to note here that in two of the O C A M D - A cats in which no recovery time was allowed after the chiasm transection, no such an invasion of callosal input was found. Callosally driven cells were found only in one animal of
RESULTS The distribution of the cortical cells according to their ocular dominance shows that in the acutely operated cats, whether early monocularly deprived ( O C A M D - A ) or not ( O C A - A ) , the cells activated via the ipsilateral eye constituted the majority of the responsive cells (Figs. 1, 2). This dominance of the ipsilateral eye is very prominent in comparison to the small minority of ipsilaterally driven cells in the normal control cats (Fig. 3). While the ipsilateral eye dominance in the chiasm-transected cats reflects the visual input of the direct intact connectivity, the minor response originating from the other eye is an indication of the absence of the direct contralateral pathways in these cats. The same contralateral response
51
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Fig. 1. Histograms showing the ocular dominance distribution of cortical cells in the visual cortex (areas 17, 18 and their boundary region) in the experimental OCAMD cats. Data are presented separately for the acute (Acute, A,B), medium chronic (M. chronic, C,D), and long chronic (L. chronic, E,F) cats according to the postoperative interval after the chiasm transection. Histograms A,C,E and B,D,F of these cats represent the responses in the hemisphere ipsilateral and contralateral to the deprived eye, respectively. The percentage distribution of cells is calculated separately for each ocular dominance group. The name of each group of cats and the side of hemisphere from which unit recording was performed with regard to the deprived eye, is indicated above the upper left corner of each histogram (CONTRA, contralateral; IPSI, ipsilateral). The number of cells studied in each hemisphere and the number of cats in each group are indicated above the right corner. Ocular dominance groups C and C>I represent cells driven either monocularly or binocularly with contralateral eye dominance, respectively; groups I and C
87 this group in which a recovery time of 1 week was given. It is interesting to note here that the results of the O C A M D - A cats are similar to those of the O C K M D cats in which monocular deprivation and chiasm transection were simultaneously performed, thus permitting no time interval between them. Firstly, most of the visually active cells in both groups of cats were ipsilaterally driven. Secondly, cells with callosal input (4.1%) were found in the hemisphere ipsilateral to the deprived eye of the O C K M D cats and practically none (0.8%) in the contralateral hemisphere, almost the same situation as in the O C A M D - A cats (Fig. 3A,B). Thirdly, there is similarity in the general hemispheric responsiveness level. In the hemisphere ipsilateral to the deprived eye of both O C A M D - A and O C K M D cats nearly 65% of the cells were visually unresponsive, while in the contralateral hemisphere the proportion of these cells in both groups of cats was practically the same (nearly 40%). Different results were obtained for the chronic groups of the O C A M D cats, in which long periods of recovery had elapsed after the chiasm transection. During this period, and unlike in the previously described acute cats ( O C A M D - A ) , an opportunity was given to the visual input to freely propagate interhemispherically via the corpus caUosum. Indeed, such a propagation took place already in the medium chronic cats (OCAMD-M) as reflected in the remarkable increase in the proportion of callosally activated cells. These cells constituted 32.9% of all cells with contralateral eye input in the hemisphere ipsilateral to the deprived eye (Fig. 1C) in comparison to
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the analogous hemisphere of the acute cats O C A M D - A (9.8%; Fig. 1A). An even higher proportion of caUosally driven cells (38.2%) was found in this hemisphere in the long chronic group (OCAMD-L; Fig. 1E). No difference, however, was found between the chronic and the acute O C A M D subgroups with regard to the contralateral hemisphere; there were no cells in that hemisphere with callosal input (Fig. 1B,D,F). The results of the O C A M D subgroups show a clear tendency for an increase in the proportion of caUosally driven cells in the hemisphere ipsilateral to the deprived tF eye as function of recovery time (following the callosal transection). This change is accompanied by a concomitant reduction in the proportion of cells with ipsilateral eye input in this hemisphere. As to the contralateral hemisphere, there were no callosaUy driven cells there, but the proportion of ipsilaterally driven cells showed a consistent increase with recovery time. In comparison, in the analogous subgroups of O C A cats a consistent increase both in the callosally driven cells and in the ipsilaterally driven cells (Fig. 2 A - F ) as function of recovery time was found. Thus, the basic difference between the O C A M D and the O C A cats is the remarkable increase, in the former group, in the proportion of callosally driven cells in the ipsilateral hemisphere, at the expense of the evacuation of these cells from the fellow hemisphere. It is worth mentioning here the changes found in the various groups of operated and normal cats with regard to the general level of responsiveness of cortical neurons.
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While in the normal cats the proportion of the visually unresponsive cells was 11.2% (Fig. 3C), it was much higher in the experimental cats. It ranged between 64.7% in the hemisphere ipsilateral to the deprived eye of the OCAMD-A (Fig. 1A) and 58.8% in the OCAMD-L cats (Fig. 1E); in the contralateral hemisphere of these cats the results were 42.8% (Fig. 1B) and 22% (Fig. 1F), respectively. Similarly, in the analogous subgroup of OCA-A cats nearly 48% of the cells were visually unresponsive in both hemispheres (Fig. 2A,B) while in the OCA-L cats the proportions were 24.7% in one hemisphere and 35.2% in the other (Fig. 2E,F). Thus, there is a clear tendency for an increase in the responsiveness level with recovery time. DISCUSSION It is evident from the results of the present study that although interhemispheric callosal transfer of interocular competition exists, it is normally maintained at a low level. Our present study has proved that the following conditions have to be fulfilled in order to induce a massive callosal transfer. (1) A permanent imbalance has to be induced in the interocular competition mechanism. This condition can be created only during the developmental period by suppressing one visual input by monocular deprivation 4,7,]3,25'29. (2) A minimal period of competition must take place between the deprived and the normal inputs. During that period the callosal
transfer increases as function of time; if this condition, however, is not fulfilled, the transfer is maintained, albeit at a minor level. (3) The involvement of the thalamocortical pathways is essential, whether during normal development or at adulthood; the present experimental model applies to the contralateral pathways. In the absence of these pathways the callosal transfer is remarkably depleted or even completely eliminated. (4) A long recovery time is needed after the chiasm transection. This has been clearly reflected in the remarkable amount of callosal transfer found in our chronic cats in comparison to the acute cats. For normal callosal transfer to exist, the presence of the whole complement of geniculocortical pathways is needed as already previously proved by us in optic chiasm 33'34- and optic tract-transected cats 28'34. In the chiasm-transected animals only a minor amount of callosal transfer has been found by us as also presently confirmed (our recent study shows a greater transfer if chiasm transection was performed developmentally31). This condition is further emphasized by the fact that in our experimental model, the cat, the decussation is asymmetric 21 and thus the majority of the direct visual input was eliminated by the chiasm transection. That the corpus callosum is the only mediator of the small amount of interhemispheric transfer of visual information found in the above-described animals, has already been proved by us previously. We showed a complete absence of callosal transfer in split brain cats, i.e., when the corpus
89 callosum was eliminated in addition to the chiasm transection29,30,32 Presently we have proved that it is possible to induce an increase in the callosal transfer if the elimination of the contralateral pathways is combined with monocular deprivation (OCAMD). This caused rerouting of the visual input to cortical cells from the conventional geniculocortical to the callosal pathway. Under this condition unidirectional interhemispheric flow of visual information was forced, due to interocular competition between the normal and the deprived eye. The conventional interocular competition mediated via the thalamocortical pathways had thus turned to being an interhemispheric competition. The input from the normal eye that travelled via the remaining callosal pathway invaded the hemisphere ipsilateral to the deprived eye to regain synaptic sites there which were abandoned by afferents from the deprived eye. This was proved by the very remarkable fact that no cells with callosal input from the deprived eye were found in the hemisphere ipsilateral to the normal eye, in sharp contrast to the presence of many callosally driven cells in the fellow hemisphere. Callosally driven cells, albeit in small proportions, were usually found in both hemispheres of our late chiasm-operated and normally exposed cats (OCA). Our findings clearly indicate that only after a long interval following the onset of monocular deprivation, the hemisphere ipsilateral to the deprived eye had accepted the indirect callosal input, as a substitution for the blocked direct input. During this period the interocular competition via the direct pathways had established in the cortex an imbalance between the normal and the deprived eye's outputs. It was indeed proved by us that in the absence of such an interval in the OCKMD cats, and as a consequence of loss of conventional interocular competition, a negligible callosal transfer exists27'35. The callosal transfer was therefore rendered ineffective in these cats due to its dependency on the conventional interocular competition. This hypothesis is not supported by the results of previous investigators showing a considerable amount of callosal transfer under the same conditionsS; the latter investigators however, found also a remarkable transfer in chiasm-transected adult cats in contradiction to our results. REFERENCES 1 Berlucchi, G. and Rizzolatti, G., Binocularly driven neurons in visual cortex of split-chiasm cats, Science, 159 (1968) 308-310. 2 Berman, N. and Daw, N.W., Comparison of the critical periods for monocular and directional deprivation in cats, J. Physiol. (Lond.), 265 (1977) 249-259. 3 Blakemore, C. and Van Siuyters, R.C., Reversal of the physiologicaleffects of monocular deprivation in kittens. Further evidence for a sensitive period, J. Physiol. (Lond.), 237 (1974)
The cancellation of the contralateral pathways induces separation of the two hemispheres to a great extent; each hemisphere becoming governed by its own, ipsilateral eye33,34. This separation is also preserved if the above operation is developmentally carried out, whether in normal 31 or in monocularly deprived kittens 27'35. In the latter, the hemisphere ipsilateral to the non-deprived eye was proved to be the 'experienced' one, as reflected in the responsiveness level of the cells there, in comparison to the fellow hemisphere. In the OCAMD cats of the present study, this condition developed in the adult cats, at a certain recovery period after the transection of the optic chiasm. It was thus proved that once the situation of the 'experienced' and 'inexperienced' hemispheres was established, in accordance with the appropriate visual inputs, the callosal transfer was triggered. In the present study, therefore, both the hemispheric difference and the callosal transfer were induced after the termination of the plasticity period, providing preconditioning by monocular deprivation had taken place during development. As to the mechanism of the interocular competition we have new evidence from the present study that it is inhibitory. When monocular deprivation was performed at an early age (first postoperative month, as in our OCAMD cats), 3.3% of all cells were monocularly driven by the deprived eye 36. In contrast, in the OCAMD-A cats of the present study, the monocularly driven cells from the deprived eye constituted 25.5% of all cells in the hemisphere ipsilateral to the deprived eye. Thus, the release from inhibitory action of the normal eye (following sectioning of the contralateral pathways), enhanced the activity of the deprived eye. This is in keeping with similar results previously found following removal of the normal eye in early monocularly deprived adult cats 8'13'14'22. However, the interocular inhibition found by us is temporary; while in the acute cats (OCAMD-A) 25.5% of the cells were driven by the deprived eye, they constituted only 2.9% in the long chronic group (OCAMD-L). The latter result is already similar to the one obtained by us for monocularly deprived cats 36. Thus, while the postcritical period interocular inhibitory mechanism is temporary, the previously described postcritical callosal transfer is permanent and was enhanced with recovery time. 195-216. 4 Blakemore, C., Van Sluyters, R.C. and Movshon, J.A., Synaptic competition in the kitten's visual cortex. In Cold Spring Harbor Symposia on Quantitative Biology, Cold Spring Harbor Laboratory, New York, 1976, pp. 601-609. 5 Cynader, M., Lepore, E and Guillemot, J.P., Interhemispheric competition during postnatal development, Nature (Lond.), 290 (1981) 139-140. 6 Cynader, M., Timney, B.N. and Mitchell, D.E., Period of susceptibility of kitten visual cortex to the effects of monocular
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