Chapter 23 Reorganization processes in the visual cortex also depend on visual experience in the adult cat

T.P. Hicks, S. Molotchnikoff and T. On0 (Eds.) Progress in Brain Research, Val. 95 0 1993 Elsevier Science Publishers B.V. All rights reserved

257

CHAPTER 23

Reorganization processes in the visual cortex also depend on visual experience in the adult cat Chantal Milleret and Pierre B u m 2 I

’

Collkge de France, Laboratoire de Neurophysiologie, 75231 Paris Cedex 05, and Institut des Neurosciences, Ddpartement de Neurophysiologie Comparde, CNRS et Universite Pierre et Marie Curie, 75230 Paris Cedex 05, France

Introduction Multiple evidences have now been provided showing that normal visual experience after birth is crucial for the maturation of the properties of visual cortical cells in kittens. Visual deprivations lead to both physiological and anatomical changes in the visual cortex (see Hirsch and Leventhal, 1978; Movshon and Van Sluyters, 1981; Sherman and Spear, 1982; Fregnac and Imbert, 1984; Hirsch, 1985; Hirsch and Tieman, 1987, for reviews). Thus, when animals are deprived of vision early in life, either through darkrearing or through binocular eyelid suture, the characteristics of the visual cells do not mature according to the normal process (Imbert and Buisseret, 1975; Blakemore and Van Sluyters, 1975; FrCgnac and Imbert, 1978; Milleret et al., 1988). After monocular deprivation, most cells in the cortex cannot be driven through the deprived eye and the animals are almost blind through that eye (Wiesel and Hubel, 1963). Until recently, susceptibility to such environmental manipulations was thought to be limited to the first few postnatal months, i.e., to the critical period (Wiesel and Hubel, 1963; Riesen, 1965; Hubel and Wiesel, 1970; Blakemore and Van Sluyters, 1974; Cynader et al., 1980; Olson and Freeman, 1980). However, some of our recent findings lead to extend such a susceptibility to the adulthood. Our experiments were prompted by a variety of

data clearly showing that plasticity of the visual system could also be characterized in the adult after partial deafferentation and that a progressive functional reorganization of this system could take place in such conditions (Galambos et al., 1967; Norton et al., 1967; Chow, 1968; Jacobson et al., 1978, 1979; Eysel, 1978, 1979; Eysel et al., 1980; Yinon, 1980; Yinon and Hammer, 1985;Kaas et al., 1990; Heinen and Skavenski, 1991). With these results in mind, the question that we addressed was whether postoperative visual experience could influence this reorganization. Our procedure was to cut the optic chiasm of adult cats midsagitally, thus depriving each hemisphere of the afferents originating from the opposite nasal retina, then to either maintain the animals in the light or in the dark or to combine the section with a monocular occlusion during a postoperative period of variable duration. In all cases, the sizes of the visual cortical receptive fields of cortical cells either activated through the direct pathway or via the corpus callosum were taken as a functional index in the final exploration achieved under anesthesia and paralysis. In a first series of experiments, we only considered the receptive field (RF) sizes of visual cortical cells recorded in area 18, activated through the direct retino-geniculo-cortical pathway. The findings show that a postoperative visual experience is necessary for a recovery to occur. In a second series, the RF characteristics of cells

258

activated through the corpus callosum were analyzed after chiasmotomy. The results demonstrate that monocular occlusion can induce an asymmetrical callosal transfer between visual cortical areas.

General methodology The experiments were performed on adult cats which had their optic chiasm sectioned midsagitally. This surgery was achieved under Saffan anesthesia (I.M. 1.2 ml/kg: 10.8 mg/kg of Alfaxolone and 3.6 mg/kg of Alfadolone acetate) via an oral approach under aseptic conditions following a standard procedure (see Myers, 1955, for details). Some of these animals were left in a normal visual environment during their postoperative period. Some others were allowed either only a monocular patterned visual experience through eyelid suture of the other eye or no visual experience at all by being left in complete darkness during this period. The postoperative period could last from 4h to 6 weeks. Some further intact animals were used as controls (see the Results section for some more details). For the final recording session, anesthesia was initially induced by Saffan injection. After cannulation of the radial vein and tracheotomy, the animals were placed in a stereotaxic apparatus designed to leave free the entire visual field. The skull was removed to gain access to the visual cortex. The animal was then paralyzed with an i.v. injection of Flaxedil. The closed eye of the monocularly deprived animals was reopened. The nictitating membrane of both eyes was retracted with neosynephrine and the pupils were dilated with atropine. Contact lenses were placed to prevent the cornea from drying off. All preparations were then maintained under permanent slow infusion of a mixture of Saffan (3.6 mg/kg per hour), Flaxedil(l0 - 15 mg/kg per hour), Plasmagel and glucose. The heart rate and pC0, (4%) were monitored throughout the experiment and the body temperature was maintained at 38°C. The positions of the optic discs were determined through back-projection with a reversible ophthalmoscope on the screen that faced the animal, at 1 m in front of its eyes. This evaluation

was made at the beginning and several times during the experiment; the position of the projection of the area centralis was then determined using the classical quantitative data provided by Vakkur et al. (1963). Extracellular recordings were achieved through a tungsten microelectrode (1 - 2 MSZ at 1000 Hz) insertedobliquelyintothevisualcortex(P5toA15; L1 to L5), either into area 17 or into area 18 or at the 17/18 border (see the Results section); after placement of the electrode, agar-agar in saline (4Vo) was poured upon the cortex to prevent drying off. The experimental procedure to isolate a single unit and to analyze its properties was as follows. (1) Spikes were amplified, visualized and audiomonitored in a conventional way. (2) Recordings were made along each tract at regular 100 pm distances whenever possible, in order to reduce sampling bias. (3) Slits and spots were projected by means of a hand-held stimulator. To detect visual responses and to avoid missing spontaneous silent units, the test stimulus was permanently moved across the screen. (4) The cell’s RF was mapped on the screen either for only one eye or for each eye successively. Receptive field borders (length and width) were defined by moving the optimal stimulus back and forth outside the RF and gradually approaching it until an overt response occurred. Since particular emphasis was placed on the receptive field sizes, special care was taken to plot these field limits. ( 5 ) The cell’s ocular dominance was also determined whenever necessary. Each electrode penetration, usually as far as 3000-4000 pm, was marked by two small electrolytic lesions (DC current; 15 FA, 15 sec) at two different depths. At the end of the experiment, the animals were perfused with formaline (4Vo) and the brain was removed. Chiasmotomy was controlled for each animal on Weil or Page stained sections (40 pm); electrode penetrations were identified on Nisslstained sections (100pm) cut in the frontal plane and were reconstructed using the electrolytic lesions as references. Using the response characteristics of the cells (Hubel and Wiesel, 1965; Harvey, 1980; Orban

259 TABLE I Experimental groups and postoperative conditions i,n the first series of experiments Experimental group

Number of cats

Postoperative delay between chiasmotomy and exploration

Postoperative visual condition

A C CN

5 10 4

4h 21 - 44 days 21 - 55 days

Binocular vision Binocular vision Complete darkness

etal., 1980;Payne, 1990;Diaoetal., 1990),combined with the morphological criteria (Otsuka and Hassler, 1962; Tusa et al., 1979), we could identify the position of the areas 17 and 18 and of the 17/18 border. Each receptive field mapped through visual stimulation of each eye was then redrawn with respect to the corresponding optic disc to determine exactly its spatial location within the visual field.

Results ,

,’

R

L

I

xo

\

Fig. 1. Overall scheme to indicate our various experimental approaches with respect to topography of visual projections. After midsagittal sectionof the optic chiasm (XO), uncrossed fibers of the optic nerve (ON) remain intact, project to the visual cortex (VCx) via the optic tract (OT), the lateral geniculate nucleus (LGN) and the optic radiations (OR). In these preparations, the visual cortical cells recorded through a microelectrode Q on one side may be excited through either the geniculo-cortical ipsilateral pathway or the callosal route (CC), by stimulating respectively theipsilateral (left, L) or the contralateral eye (right, R). In the first series of experiments, only the functional properties of cortical cells recorded in area 18 (18) and visually activated from the ipsilateral eye (left eye, arrow) were analyzed. In the second series, the situation was more complex (see Fig. 4).

First part: maintaining in the dark prevents any recovery of the direct retino-geniculo-cortical pathway after section of the optic chiasm in the adult cat ~ ~ i ~ l eand r e Buser, t 1984) In this first series of experiments, the 19 adult cats which underwent a midsagittal section of their optic chiasm were divided into three experimental groups: two were maintained with binocular vision but differed by their postoperative delay (A group, 4 h; C group, 21 -44 days); the remaining one (CN group) was placed in complete darkness for 21 - 55 days before the final exploration (Table I). Five further intact animals were placed under the same experimental conditions for electrophysiological study (see the Methodology section) and served as control (T) group. A total of 357 recorded cells could be studied for their reactivity to visual stimulation of the eye ipsilateral to the investigated cortex (area 18; Fig. 1). Their distribution among groups was as follows: T,

260

150

100

50

0

T

A

G

CN

Fig. 2. Mean RF areas (S, in deg’) in the T, A, C and CN experimental groups, respectively (see text and Table I for definition of groups). Confidence limits at P = 0.05; n, number of cells. (Modified from Milleret and Buser, 1984.)

88; A, 84; C, 107; CN, 78. Between group comparisons were made possible since recordings were all performed in the same cortical zone, extending from the projection zone of the horizontal meridian to that of the lower part of the visual field. The majority of these cells displayed well circumscribed receptive fields. They could be classified as simple, complex or hypercomplex, using the most commonly accepted criteria (Hubel and Wiesel, 1962, 1965). In a first analysis, it appeared that the mean RF sizes were different in the various experimental groups (Fig. 2): (i) this mean displayed a highly significant reduction in the A group (50 deg2) with respect to the control animals (T, 125 deg2); this reduction was about equal to a factor of 3; (ii) on the other hand, the mean size was much larger in the C group, which had a long postoperative period (122 deg2), the difference between this group and the T group being no longer significant (at P = 0.05); thus, a complete recovery seems to occur within 6 weeks after the chiasmotomy; (iii) no such restoration took place in animals maintained in the dark during the postoperative period after partial deafferentation (CNgroup); their mean RF size remained at low values (46 deg2), even after postoperative periods as long as 55 days.

We then tried to establish which kind of RFs (central and/or peripheral) were relatively more affected by chiasmotomy and which ones had undergone some recovery. Fig. 3 illustrates this analysis and shows that large RFs which prevail at relatively high eccentricities in control animals (in agreement with other authors, such as Hubel and Wiesel, 1965) disappeared in the A group and were restored in the C group. Again, no such recovery could be observed in the CN animals. In addition to these cells with circumscribed RFs, units with diffuse responses were also encountered, particularly in the C group (9% against 1 - 2.5% in the other groups T, A and CN). Visual experience after chiasmotomy thus seems to favor the appearance of a few abnormal visual responses; in absence of such an experience, the development of these abnormalities is prevented.

Second part: a monocular occlusion elicits an asymmetrical callosal transfer between visual cortical areas in optic chiasm sectioned adult cats The effects of a monocular occlusion were studied in areas 17 and 18 and at the boundary between both areas by comparing the cortical location of cells activated via the corpus callosum, as well as the spatial distribution and sizes of their RFs in several distinct experimental groups (Fig. 4, first column). The first two groups (XO, and XO,) only underwent a midsagittal section of the optic chiasm and were explored, either 2 - 3 days (XO,, n = 7) or 6 weeks (XO,, n = 5) later on. The postoperative visual experience was here binocular. In the two other groups (MOXO, and MOXO,), the optic chiasm section was combined with an occlusion of the right eye. Callosal transfer of visual information was then analyzed 6 weeks later on, through visual stimulation of either the eye that had remained open (MOXO,, n = 1 1) or the one which had been closed (MOXO,, n = 7) throughout the postoperative period. In total, 1371 cells were recorded. Among these neurons, 304 could be activated through interhemispheric transfer (C + ,Table 11). The callosal origin of these interhemispheric activities was clear-

26 1

T

C

n=86

n=97

A

17-83

CN

n =76

Fig. 3. Distribution of receptive field areas as a function of their location in the visual field in the T, A, C and CN groups. Az, Azimuth in degrees (x axis); E, elevation in degrees (y axis); S, receptive field area in d e 2 (z axis). Each dot in the A z - E plane indicates the geometrical center of a given visual receptive field, the area of which is plotted as S. n, Number of cells. (Modified from Milleret and Buser, 1984.)

ly established, at least in part, in the preparations (XO,, 1 out of 5 animals; MOXO,, 6/10; MOXO,, 3/4) through local application of procaine upon the visual cortex of origin (Fig. 5 ) . An analysis of the cortical location of these C + cells in the different groups (Table 11) first showed that they were mainly located at the 17/18 border. In this cortical region, their percentage was always about 50Vo (XO1, 54%; XO,, 49%; MOXO,, 53%;

MOXO,, 60%). A few cells (2- 10Vo) were also located either in area 17or in area 18. Monocular occlusion thus does not seem to alter the cortical tangential extent of the C + cells. As a general rule, the receptive fields of these C + cells (mainly complex cells) were centered near or on the central vertical meridian of the visual field whatever the recording site (Fig. 4, second column). This particular feature of the cells activated through

262

1

2

3

/

xol

.f -W

10'

"t

20' *I

n

.48

m = 10.6f2.8

100 0

100 200 300 400 500 Sq2

El

L n =56 m =43*6.3

10 0

MOXOl /

I00 200 240 4po 500 sqz

El

:i,L n

=

73

m =lo8f 28

10

0

El

1

100 200 300 400 500 600 Sqz

501 n .47 m

10 0

= 16.623.1

100 ZOO 300 400 500 Sq'

263 TABLE 11 Number of cortical cells in the different experimental groups (XO,, XO,, MOXO,, MOXOJ in the second series of experiments as a function of the recording site Experimental group

Area

Total

A 17

XOl XO, MOXO, MOXO,

n = 7

n= 5 n = 11 n =

7

A 18

17/18

Non loc.

number

C+

C-

C+

C-

C+

C-

C+

C-

3 6 4 1

126 0 66 52

52 49 77 39

44 50 67 25

0 12 9 12

64 217 76 154

5 10 27 3

65 35 18 3

359 379 344 289

A 17, area 17; 17/18, 17/18 border; A 18, area 18; Non loc., non localized cells. n , Number of cats; C + , callosal driven cells; C - , cortical cells non-activated through the corpus callosum.

the corpus callosum (Choudhury et al., 1965; Vesbaesya et al., 1967; Berlucchi and Rizzolatti, 1968; Harvey, 1980; Lepore and Guillemot, 1982; Payne et al., 1991) had thus been maintained as well, in spite of the monocular occlusion. Notice that, at least in three groups (XO,, XO, and MOXO,), a marked displacement toward the hemifield ipsilateral to the explored cortex clearly appeared, especially outside of the area centralis projection zone (see Fig. 4, second column). Some marked inter-group specific differences could also be observed. Among these, the most significant and surprising one concerned the maximal lateral extent of the C + receptive fields in the visual field, with respect to the central vertical meri-

dian. Whereas in the XO, group the C + receptive field extension did not exceed 7 - 9" of eccentricity on both sides of the meridian, it could reach up to 15" in the X0 2 group, especially in the hemifield ipsilateral to the explored cortex. In the MOXO, group, this extension could be as high as 25" while it only reached 7' in the MOXO, group. Another surprising but significant difference, which is clearly and certainly closely related to the previous one, concerned the receptive field size of the C + cells (Fig. 4, third column). Three days after optic chiasm section (XO, group), the mean receptive field size of these C + cells was very small (10.6 k 2.8 deg2)but it significantly increased with the postoperative delay to reach 43 f 6.3 deg2 six

Fig. 4. Experimental designs and results. First column. Summary of the four experimental protocols. XO, and XO,, adult cats with transected optic chiasm which were allowed binocular visual experience throughout the postoperative period (3 days or 6 weeks, respectively). In this series, the interhemispheric transfer was tested by stimulating the left eye (L, see arrow) and recording units from the contralateral visual cortex (VCx) in areas 17 and 18 b).The right eye (R), ipsilateral to the recording side, was simply masked during the exploration except to test for the ocular dominance of the recorded cells. Abbreviations ON, XO, OT, OR, CGL and CC, see Fig. 1 . MOXO, and MOXO,, animals with transected optic chiasm and monocular occlusion of the right eye during the whole postoperative period (6 weeks, double arrow); the eye was opened only on the day of the final exploration and masked when necessary. In the MOXO, group, the studied transfer was that from the left eye through the left cortex to the right one; in the MOXO,, the reverse traffic was investigated, i.e., from the right eye (deprived one) through the right cortex to the left one. Secondcolumn. Spatial distribution of receptive fields of cortical neurons activated through the corpus callosum in the four groups XO,, XO,, MOXO, and MOXO,, respectively. Az, Horizontal meridian; El, central vertical meridian. Each rectangle corresponds to the receptive field of one cell. OD and OG, right and left optic discs. Thirdcolumn. Distribution of the areas (in deg2)of the RFs drawn in column 2, for each experimental situation. n, Population of cells whose receptive fields could be determined; m, mean receptive field area with confident limits at P = 0.05. Bin width, 50 deg2.

264

+

El

1 c-

-t 2

10"

-10"

Kylocaine 4pplication

visstim.

\

Fig. 5 . Demonstration of the callosal origin of the recorded interhemispheric activities in a cat belonging to the MOXO, group (MOX0,J. A . On the left, general experimental protocol (see Fig. 4 for comments); on the right, 12 successive visual responses of a cortical cell activated through an interhemispheric transfer, recorded from the right cortex, represented as a dot display (control response). The visual stimulations consisted in forth and back ramp movements of a slit automatically driven across the receptive field. Both the receptive field and the extreme positions of the slit (hatched areas) are represented in the central panel: 1 corresponds to the first movement of the slit (first part of the ramp) and 2 to the second one (second part of the ramp); El, elevation; Az, azimuth. B. At left, experimental protocol with procaine application on the source cortex of the callosal message topographically symmetrical to recording site (left cortex), to demonstrate the callosal origin of the visual responses recorded on the right cortex; at right, the visual response of the cell was completely suppressed 20 min after procahe application.

265

XO2

200

]

n

:

56

G = 43 + 6 3

10

0

30

20

40

50

I1 : 73 %:lo8 ? 2 8

.. 500

MOXOl

400

.

300

.

200

.

._ .

0

10

.

I

*

a:.

20

30

A

50

11 :47

100

.:> 0

40

.....*. .

..*.

:: .,.* 10

20

30

40

50

Fig. 6. Surface (S in deg2) of RFs of callosal activated cortical cells, recorded from A17 (17, open circles), A18 (18, black triangles) and at the 17/18 border (17- 18, black points) as a function of the eccentricity (E in degrees) of their geometrical center (see text) in the different experimental groups XO,, XO,, MOXO, and MOX02. n, Number of cells; m, mean receptive field area with confidence limits at P = 0.05.

weeks after section (XO, group). In other words, the mean surface became about 4 times larger within a 6 week period. Whereas these last values were the same in both cortices, some asymmetry appeared in the MOXOs. In the MOXO, group, some receptive fields of cells recorded in the “deprived” cortex 6 weeks after the optic chiasm section were as small as in the control groups XO, and XO, (< 100 deg2); on the other hand, some others were very much larger (600 deg2). As a consequence, the mean RF size reached 108 k 28 deg2. Conversely, in the

MOXO, group, the RF size of the C + cells recorded in the “non-deprived” cortex was as small as in theXOlgroupwithameanequalto 16.6 f 3.1 deg2 in spite of the 6 weeks of postoperative delay. The difference was significant between all the experimental groups compared by pair except for the XO, and MOXO, ones (Kolmogorov - Smirnov non-parametric test at 5%). Three further interesting observations could be obtained from these last data by studying the evolution of the C + receptive field size as a function of the distance (“eccentricity”) of their geometrical center from the area centralis projection (Fig. 6). Firstly, this particular RF population did not increase their size from the center to the periphery of the visual field. In this respect, they are completely different from the whole population of visual cortical cells (Hubel and Wiesel, 1965; see also the first part of this section). Secondly, the C + RFs increase in size with the postoperative delay (XO, and MOXO, groups compared to the XO, group) whatever the recording site of the corresponding cells. As a third point, it seemed that receptive fields in area 18 were somewhat larger than those in either area 17 or at the 17/18 border, particularly in the XO, and MOXO, groups. Although the analysis of the RF size was the main aim of this study, some other characteristics of the C + cells were also investigated such as their ocular dominance. From this analysis, it appeared that the monocular occlusion, in our experimental conditions, did not modify the distribution of this property: in all cases, most of the C + cells (about 70%) were better activated through the direct retinogeniculo-pathway (i.e., from the ipsilateral eye to the explored cortex) than through the corpus callosum (from the contralateral eye). Other C + cells were either binocular or dominated by the contralateral eye. Discussion

Both series of data presentedin this paper lead to the conclusion that functional reorganization in the visual cortex of the adult cat after partial deafferen-

266

tation depends on visual experience. Susceptibility to at least some environmental manipulations thus extends beyond the critical period. Discussing our data, one may first wonder whether a partial deafferentation is really compulsory to identify this susceptibility. Such a question may be asked by considering at least two different series of data. Creutzfeldt and Heggelund (1975) have described some plastic changes in the visual cortex of intact adult cats after exposure to visual stripes. These data may, however, be interpreted rather as a bias in eye movements induced by the exposure to a particular pattern than as an effect of environmental manipulation. In favor of this latter interpretation, observations exist showing that in the adult some properties of visual cortical cells can be altered through either monocular paralysis (Buchtel et al., 1972; Fiorentini and Maffei, 1974; Maffei and Fiorentini, 1976) or eye rotation (Singer et al., 1982). The other series of data concerns the period of susceptibility to monocular occlusion which in the young animal has been so far defined on the basis of the ocular dominance (Wiesel and Hubel, 1963; Hubel and Wiesel, 1970; Blakemore and Van Sluyters, 1974; Cynader et al., 1980; Olson and Freeman, 1980). One thus ignores whether such a deprivation can act upon some other characteristics of the cortical cells such as, for instance, the size of their RFs beyond 3 months of age. In our MOXO, group (see second part of the Results section), the RFs of the callosally activated cells were larger than in the XO, control group. This may be interpreted in two ways: either monocular occlusion needs to be combined with chiasm section to elicit the enlargement as observed after 6 weeks, or 6 weeks of monocular occlusion are sufficient to produce this enlargement. To answer this question, we have recently separated the occlusion and the chiasmotomy, the latter being achieved 6 weeks after the occlusion and immediately followed by the exploration. The preliminary results indicate no widening of the RFs, suggesting that the two manipulations need to be combined. Exceptions do exist, however, regarding the necessity to achieve as complex

manipulations as ours to get any reorganization in the adult. Those concern local interventions on adult cortical cells, whose ocular dominance, orientation selectivity and RF size could be altered either through current injection (FrCgnac et al., 1988) or after transplantation of cultured astrocytes (Miiller and Best, 1989). However, considered altogether, all these data indicate that changes in visual cortical cell properties can override the classical critical period provided that some adequate manipulations be achieved. Although our two series of experiments concerned different visual routes, the results were coherent enough to allow some general conclusions on the role of partial deafferentation and visual experience in the observed reorganizations. (1) Partial deafferentation decreases the RFsizes. This reduction was particularly clear in the first series of results when comparing the T and A groups. In the second series, such reduction could only be inferred, since callosal activation cannot be directly evaluated in an intact reference group. Our next point may, however, justify extrapolation when comparing XO, and XO, groups. (2) A visual experience of an adequate duration (6 weeks in our case) inducessome reorganization after partial deafferentation. This appears when comparing different groups two by two: the A and C groups in the first part of the Results section; XO, and XO,, XO, and MOXO,, XO, and MOXO, in the second part of the Results section. Comparing A and C groups, recovery occurred only after postoperative visual experience. The same type of recovery can be inferred to occur in the second pair, between XO, and XO,, supposing that XO, became equal to intact animal. This assumption seems justified since the “callosal” RF mean area increased in approximately the same proportion as the C with respect to the A group (3 - 4 times). Comparison of the other pairs (XO, and MOXO,; XO, and MOXO,) indicated that visual experience produces some reorganization, with the final state differing from the initial control one. These changes, recovery or reorganization, took

267

place within 6 weeks after chiasmotomy. This delay is in agreement with most of the previous investigations describing such processes in the visual system of adult cats (Galambos et al., 1967; Norton et al., 1967;Eysel, 1978; Jacobsonet al., 1979;Eyselet al., 1980; Yinon, 1980; Kaas et al., 1990). Recently, Yinon and Milgram (1990) could not reproduce our results on the MOXO, group, in spite of the 4 - 11 months delay. The comparison is difficult, however, since they did not record any consistent interhemispheric transfer even in the control animals. ( 3 ) Maintaining in the dark prevents any reorganization to occur. This point is particularly clear when comparing C and CN groups (Results section, first part): the mean RF size in the CN group remained as small as in the A group, in spite of the 6 weeks of postoperative delay. The same type of phenomenon seems to occur for the C + RFs of the MOXO, group, which were as small as those of the XO, group (Results section, second part). In other words, visual deprivation (through either darkmaintaining or monocular occlusion) prevented any reorganization to occur, at least within 6 weeks: the system seems to be “frozen” in the state which was present immediately after the partial deafferentation. The persistence of visual activity thus appears to be necessary for a reorganization to occur in the visual system in the adult. This seems a more general rule since the same type of condition (persistence of functioning) for recovery or reorganization was reported to be required by Merzenich and colleagues in their study of the somatosensory system (Merzenich et al., 1988). It should be stressed here that the changes that we could observe at the cortical level may not necessarily have been exclusively located at this upper level, but may well reflect some subcortical modifications. Actually, a few data are available so far in favor of this latter possibility, since it is known that the activity of the lateral geniculate nucleus is affected through partial deafferentation with some recovery being possible later on (Eysel, 1978, 1979; Eysel et al., 1980). A large number of mechanisms have, at the pres-

ent time, been suggested to account for the reorganization processes in the central nervous system: sprouting and synaptogenesis, temporary loss of responsiveness (diaschisis), hypersensitivity of remaining synapses, switching of functional activity among residual circuitry or activation of previously existing but normally ineffective synaptic contacts. More recently, long-term potentiation or long-term depression have also been put foward, the more so since these have been described at the cortical level in the visual system of the adult (Artola and Singer, 1987; Artola et al., 1990), and are proposed as a possible mechanism for plasticity (BenAri and Represa, 1990). So far, we cannot determine which of these mechanisms are really involved. However, the present data may provide one further model for studying environmental dependence for reorganization in the adult.

References Artola, A. and Singer, W. (1987) Long-term potentiation and NMDA receptors in rat visual cortex. Nature, 330: 649 - 652. Artola, A., Brocher, S. and Singer, W. (1990) Different voltagedependent thresholds for inducing long-term depression and long-term potentiation in slices of rat visual cortex. Nature, 347: 69-72. Ben-Ari, Y. and Represa, A. (1990) Brief seizure episodes induce long-term potentiation and mossy fibre sprouting in the hippocampus. Trends Neurosci., 13: 312- 317. Berlucchi, G. and Rizzolatti, G. (1968) Binocularly driven neurons in visual cortex of split-chiasm cats. Science, 159: 308 - 310. Blakemore, C. and Van Sluyters, R.C. (1974) Reversal of the physiological effects of monocular deprivation in kittens: further evidence for a sensitive period. J. Physiol. (Lond.)., 237: 195 - 216. Blakemore, C. and Van Sluyters, R.C. (1975) Innate and environment factors in the development of the kitten’s visual cortex. J. Physiol. (Lond.), 248: 663-716. Buchtel, H.A., Berlucchi, G . and Mascetti, G.G. (1972) Modification in visual perception and learning following immobilization of one eye in cats. Bruin Res., 37: 355 - 356. Choudhury, B.P., Whitteridge, D. and Wilson, M.E. (1965) Q. J. Exp. Physiol., 50: 214 - 219. Chow, K. (1968) Visual discrimination after extensive ablation of optic tract and visual cortex in cats. Brain Res., 9: 363 - 366. Creutzfeldt, O.D. and Heggelund, P. (1975) Neural plasticity in visual cortex of adult cats after exposure to visual patterns.

268

Science, 188: 1025 - 1027. Cynader M., Timney, B.N. and Mitchell, D.E. (1980) Period of susceptibility of kitten visual cortex to the effects of monocular deprivation extends beyond six months of age. Brain Res., 191: 545 - 550. Diao, Y.C., Jia, W.G., Swindale, N.V. and Cynader, M.S. (1990) Functional organization of the cortical 17/18 border region in the cat. Exp. Brain Res., 79: 271 - 282. Eysel, U.T. (1978) Late effects of deafferentation and signs of plasticity in the lateral geniculate nucleus of the adult cat after monocular lesions of the retina. Arch. Ital. Biol., 116: 309 - 3 18. Eysel, U.T. (1979) Maintained activity, excitation and inhibition of lateral geniculate neurons after monocular deafferentation in the adult cat. Brain Res., 166: 259-271. Eysel, U.T., Gonzales-Aguilar, F. and Mayer, U. (1980) A functional sign of reorganisation in the visual system of adult cats: lateral geniculate neurons with displaced receptive fields after lesions of the nasal retina. Brain Res., 181: 285 - 301. Fiorentini, A. and Maffei, L. (1974) Change of binocular properties of the simple cells of the cortex in adult cats following immobilization of one eye. Vision Rex, 14: 217-218. Fregnac, Y. and Imbert, M. (1978) Early development of visual cortical cells in normal and dark-reared kittens: relationship between orientation selectivity and ocular dominance. J. Physiol. (Lond.), 278: 27 - 44. FrCgnac, Y. and Imbert, M. (1984) Development of neuronal selectivity in primary visual cortex of cat. Physiol. Rev., 64: 325 - 434. Fregnac, Y., Shultz, D., Thorpe, S. and Bienenstock, E. (1988) A cellular analogue of visual cortical plasticity. Nature, 333: 367 - 370. Galambos, R., Norton, T.T. and Frommer, G.P. (1967) Optic tract lesions sparing pattern vision in cats. Exp. Neurol., 18: 8 - 25. Harvey, A.R. (1980) The afferent connections and laminar distribution of cells in area 18 of the cat. J. Physiol. (Lond.), 302: 483 - 507. Heinen, S.J. and Skavenski, A.A. (1991) Recovery of visual responses in foveal V1 neurons following bilateral foveal lesions in adult monkey. Exp. Brain Res., 83: 670-674. Hirsch, V.H.B. (1985) The tunable seer. Activity - dependent development of vision. In: E.M. Blass (Ed.), Handbook of Behavioral Neurobiology, Vol. 8, Plenum, New York, pp. 237 - 295. Hirsch, V.H.B. and Leventhal, A.G. (1978) Functional modificationof the developing visual system. In: M. Jacobson (Ed.), Development of Sensory Systems, Springer Verlag, Berlin, pp. 279 - 335. Hirsch, V.H.B. and Tieman, S.B. (1987) Perceptual development and experience-dependent changes in cat visual cortex. In: M. Bornstein and N.J. Hillsdale (Eds.), Sensitive Periods in Development: Interdisciplinary Perspectives, Lawrence Erlbaum, NJ, pp. 39-79.

Hubel, D.H. and Wiesel, T.N. (1962) Receptive fields, binocular interaction and functional architecture in the cat’s visual cortex. J. Physiol. (Lond.), 160: 106- 154. Hubel, D.H. and Wiesel, T.N. (1965) Receptive fields and functional architecture in two nonstriate visual areas (18 and 19) of the cat. J. Neurophysiol., 28: 229 - 289. Hubel, D.H. and Wiesel, T.N. (1970)Theperiodof susceptibility to the physiological effects of unilateral eye closure in kittens. J. Physiol. (Lond.), 206: 419 -436. Imbert, M. and Buisseret, P. (1975) Receptive field characteristics and plastic properties of visual cortical cells in kittens reared with and without visual experience. Exp. Brain Res., 22: 25 - 36. Jacobson, S.G., Eames, R.A., Evans, M. J. and McDonald, W.I. (1978) Optic nerve lesions sparing spatial vision in adult cats. Presented at the Association for Research in Vision and Ophthalmology Meeting, Saragosa, FL. Jacobson, S.G., Eames, R.A. andMcDonald, W.I. (1979) Optic nerve fibre lesions in adult cats: pattern of recovery of spatial vision. Exp. Brain Res., 36: 491 - 508. Kaas, J.H., Krubitzer, L.A., Chino, Y.M., Langston, A.L., Polley, E.H. and Blair, N. (1990) Reorganization of retinotopic cortical maps in adult mammals after lesions of the retina. Science, 248: 229 - 231. Lepore, F. andGuillemot, J.P. (1982) Visual receptive field properties of cells innervated through the corpus callosum in the cat. Exp. Brain Res., 46: 413 - 424. Maffei, L. and Fiorentini, A. (1976) Asymmetry of motility of the eyes and change of binocular properties of cortical cells in adult cats. Brain Res., 105: 73-78. Merzenich, M.M., Recanzone, G., Jenkins, W.M., Allard, T.T. and Nudo, R.J. (1988) Cortical representational plasticity. In: P. Rakic and W. Singer (Eds.), Neurobiology of Neocortex S. Bernhard Dahlem Konferenzen, Wiley, New York, pp. 41 - 67. Milleret, C. and Buser, P . (1984) 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: 73 - 81. Milleret, C., Gary-Bobo, E. and Buisseret, P. (1988) Comparative development of cell properties in cortical area 18 of normal and dark-reared kittens. Exp. Brain Res., 71: 8 -20. Movshon, J.A. and Van Sluyters, R.C. (1981) Visual neural development. Annu. Rev. Psychol., 32: 477 - 522. Miiller, C.M. and Best, J. (1989) Ocular dominance plasticity in adult cat visual cortex after transplantation of cultured astrocytes. Nature, 342: 427 - 430. Myers, R.E. (1955) Interocular transfer of pattern discrimination in cats following section of crossed optic fibres. J. Comp. Physiol. Psychol., 48: 470-473. Norton, T.T., Galambos, R. and Frommer, G.P. (1967) Optic tract lesions destroying pattern vision in cats. Exp. Neurol., 18: 26-37. Olson, C.R. and Freeman, R.D. (1980) Profile of the sensitive

269

period for monocular deprivation in kittens. Exp. Brain Res., 39: 17-21. Orban, G.A., Kennedy, H. and Maes, H. (1980) Functional change across the 17 - 18 border in the cat. Exp. Brain Res., 39: 177- 186. Otsuka, R. and Hassler, R. (1962) Uber Aufbau und Gliederung der corticalen Sehsphare bei der Katze. Psychiat. Nervenkrankh., 203: 212-234. Payne, B.R. (1990) Representation of the ipsilateral visual field in the transition zone between areas 17 and 18 of the cat’s cerebral cortex. Visual Neurosci., 4: 445 -474. Payne, B.R., Siwek, D.F. and Lomber, S.G. (1991) Complex transcallosal interactions in visual cortex. VisualNeurosci.,6: 283 - 289. Riesen, A.H. (1965) Effects of visual deprivation on perceptual function and the neural substrate. In: Deafferentation Experimentale et Clinique - Symposium Be1 Air II, Masson, Paris, pp. 47- 297. Sherman, S.M. and Spear, P.D. (1982) Organization of visual pathways in normal and visually deprived cats. Physiol. Rev., 62: 738 - 855. Singer, W., Tretter, F. and Yinon, U. (1982) Evidence for longterm functional plasticity in the visual cortex of adult cats. J. Physiol. (Lond.), 324: 239 - 248.

Tusa, R.J., Rosenquist, A.C. and Palmer, L.A. (1979) Retinotopic organization of areas 18 and 19 in the cat. J. Comp. Neurol., 185: 657 - 678. Vakkur, G.J., Bishop, P.O. and Kozak, W. (1963) Visual optics in the cat including posterior nodal distance and retinal landmarks. Vision Res., 3: 289-314. Vesbaesya, C., Whitteridge, D. and Wilson, M.E. (1967) Callosal connections of the cortex representing the area centralis. J. Physiol. (Lond.), 191: 79 - 80. Wiesel, T.N. and Hubel, D.H. (1963) Single-cell responses in striate cortex of kittens deprived of vision in one eye. J. Neurophysiol., 26: 1003 - 1017. Yinon, U. (1980) Monocular deafferentation effects on responsiveness of cortical cells in adult cats. Brain Res., 199: 299 - 306. Yinon, U. and Hammer, A. (1985) Optic chiasm split and binocularity diminution in cortical cells of acute and chronic operated adult cats. Exp. Brain Res., 58: 552-558. Yinon U . and Milgram, A. (1990) The ocular dominance and receptive field properties of visual cortex cells of cats following long-term transection of the optic chiasm and monocular deprivation during adulthood. Behav. Brain Res., 38: 163 - 173.