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Recovery in visual cortical neurons following total visual deafferentation
Brain Research, 74 (1974) 105-117
© Elsevier Scientific Publishing Company, Amsterdam- Printed in The Netherlands
RECOVERY IN VISUAL CORTICAL VISUAL D E A F F E R E N T A T I O N
NEURONS
FOLLOWING
105
TOTAL
TAKUJI KASAMATSU* ANDW. ROSS ADEY Department of Anatomy and Brain Research Institute, University of California at Los Angeles, Los Angeles, Calif. 90024 (U.S.A.)
(Accepted January 10th, 1974)
SUMMARY Long-term effects of total visual deafferentation on the functional organization of the visual cortex were studied in freely behaving adult cats. Single unit activity in control records was compared with findings immediately after bilateral enucleation and after one month. Neuronal activity one month after enucleation was intermediate between control records and those immediately after enucleation, as revealed in the pattern and rate in maintained unit activity, unit responsiveness to geniculate stimulation, and in firing correlates of ponto-geniculo-occipital waves. The results suggest restoration of some basic cortical organizations in terms of neural excitability changes in shifting states o f vigilance.
INTRODUCTION Clinical E E G studies have described abnormal electrical activity in both the congenitally blind and subjects blinded after birth. The abnormality most frequently reported was paroxysmal EEG activity in the occipital area 7,20,25. Substantial reduction in occipital alpha rhythm has also been observedT,9,13. Nevertheless, except in cases ofretinitis pigmentosa, for example, where other forms of congenital defect are common 21,2z, these blinded subjects appear to have normal brain functions apart from the defect in visual perception. On the other hand, it has been reported that subjects blinded in later life tend to retain visual dream imagery with accompanying REMs, while the congenitally blind and those blinded in early life do not have either visual * Present address: Max-Planck-Institut fiir biophysikalische Chemie, D-3400 G6ttingen-Niko lausberg Postfach 968, G.F.R.
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dreams or REMs, and the predominant sensory modality in their dreams is auditory 5,6. Recently a unique approach has demonstrated that blind subjects may have a substitute for spatial perception through visual inputs including an experience equivalent to the visuomotor senseZ, 3. In these studies tactile receptors on the skin of the back substituted for visual afferents. The visual information from a TV camera is conveyed to the CNS through tactile receptors. A basic assumption in explaining this ability is that the deafferented visual cortex itself still maintains, at least in part, the original neuronal networks responsible for visual sensation. It was previously suggested that in chronically blinded adult cats some compensatory or recovery process partly restored some basic neural organization in the visual cortex to offset an initial dysfunction following total visual deafferentation 19. It was also shown that neural activity in nonspecific sensory neurons of the mesencephalic reticular formation decreased immediately after total visual deafferentation but tended later to recover its original level 14. This report provides further data in support of the proposed possibility of reorganization of visual cortical neuron nets with respect to maintained and evoked single unit activity recorded in cats without visual inputs. Records were obtained from each animal first with the intact visual cortex, then immediately after the complete elimination of visual inputs, and finally 1 month after surgery. Some characteristics of visual cortical neurons which we may attribute to intracortical neural circuits showed definite trends toward restoration of original features but others involving the geniculocortical radiations did not. Results 1 month after enucleation are referred to as 'recovery' and those immediately after surgery as 'enucleated'. METHODS
Four adult cats were used. Bipolar electrodes were implanted under general anesthesia in the left sensorimotor cortex (SMC), the left visual cortex (VC) and the right lateral geniculate body (LGB). These electrodes monitored background EEGs. In order to hold a hydraulic microdrive a metal pedestal was also placed above the posterolateral gyrus in the right occipital area (its center located at AP, - - 2 to - - 4 mm; ML, 2 - 4 ram). In the present experiment recordings were made 30-41 days after surgical removal o f the eyes under barbiturate anesthesia. The animals received an injection of Bicillin (600,000 units) every other day for a week postoperatively. Tungsten microelectrodes insulated with Araldite 985E (Ciba) were used. At the conclusion of the experiment the animals were sacrificed under barbiturate anesthesia. The brains were fixed in 1 0 ~ formalin. Microelectrode tracks were reconstructed from serial histological sections 10/~m thick on the basis of both mierodrive readings and microlesions made at the lowest points of each penetration. The animal was kept in a dim-lit observation box during each recording session which lasted usually for several hours. They were unrestrained and able to move freely. Recording conditions were classed in 3 states described previously15-lv: (1) resting arousal (RA) with desynchronized EEG in the SMC. The cat sat or crouched quietly without vigorous body movements; (2) light sleep (LS) with high-amplitude synchronized cortical EEGs;
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Fig. 1. Three sample records of unit discharges (Unit) in the visually deafferented visual cortex in resting arousal. Unit records were obtained a month after bilateral eye enucleation, concurrently with EEGs from the contralateral visual cortex (VC) and the ipsilateral lateral geniculate body (LGB).
A: the unit tended to fire phasically in association with rhythmic slow wave bursts in the VC. B: the sustained discharge was blocked in association with rhythmic slow wave bursts in the VC. Note the trend for a short-burst firing pattern• C: no definite relation between unit firing and the EEG pattern in the VC. Time mark, 5 sec. (3) deep sleep (DS or REM) with desynchronized cortical EEGs and silent cervical E M G . Ponto-geniculo-occipital (PGO) waves were observed in the LGB and the VC. Details of experimental techniques were presented elsewhere 1~-1s. RESULTS
(1) Discharge pattern characteristics Our previous studies described characteristic changes in unit discharge patterns in the VC immediately after total visual deafferentation17,18. The visual cortical E E G during R A showed rhythmic synchronous slow wave bursts in an otherwise desynchronized record. These bursts were still observed 1 month after enucleation. However, the proportion of units which correlated with rhythmic slow wave bursts was lowered after 1 month, suggesting a decline in this hypersynchronous trend in the deafferented VC. In Fig. 1, 3 different correlates with slow E E G waves are shown, as with units tested immediately after enucleation. As exemplified in A and B, single unit activity had either an excitatory ( n = 4 units) or an inhibitory (n----3 units) relation with rhythmic slow wave bursts in the background. As seen in Fig. 1C, however, a majority o f
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Fig. 2. Coefficient of variation of interspike intervals in controls (left, N 28 units), immediately after enucleation (middle, N = 23 units) and in recovery stage (right, N = 20 units). Three behavioral states were recognized, i.e., resting arousal (RA), light sleep (LS) and deep sleep (DS). All units discharged rather fast (> l/sec) and were recorded long enough to count a minimum of 300 spikes per epoch. Mean (MEAN) and standard deviation (S.D.) are shown at the bottom of each axis. Note a general trend toward increased variability of firing in the early enucleated stage and its subsidence in later recovery.
deafferented units (24 o f 31 units) showed no definite correlation with rhythmic slow wave bursts. The proportion of non-related units in the recovery stage was significantly larger than in the enucleated stage (46 o f 97 units) (Z2 test, P < 0.01). This restorative feature in discharge patterns 1 month after deafferentation was also noted in the coefficient o f variation o f interspike intervals. Fig. 2 shows how the coefficient o f variation in unit discharge intervals fluctuates in the 3 behavioral states throughout the 3 experimental stages. As mentioned previously 17, no significant difference was noted in the overall mean interspike interval before and after enucleation. However, when we compare measures obtained in the same behavioral states during the 3 experimental stages, the coefficient o f variation o f discharge intervals tended to larger values immediately after enucleation and became smaller again in the recovery stage irrespective o f vigilance levels.
(2) Sampling incidence of the three types of VC units The 3 different types o f units were noted previously in the intact in and the deafferented VC 17 according to the correlation function between mean discharge rates in R A and changes in rate with shifts into LS. The correlation function was introduced to evaluate quantitatively, on the basis o f mean discharge rate o f individual neurons, the average responsiveness o f a neuron population to tonic central influences which determined the direction and the amount o f excitability changes o f individual neurons in shifting vigilance levels. Assumed that excitation or inhibition maintained by these tonic central mechanisms works on each cortical neuron in a similar way, the
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'i Fig. 3. Extent of change in unit discharge rates in shifting into light sleep (LS) as a function of the mean discharge rate in resting arousal (RA). Differences of mean discharge rates in RA and LS (ordinates) were plotted against mean discharge rates per sec in R A (abscissae) on a full logarithmic scale. A and B (for 77 intact units) and C and D (for 68 deafferented units) are taken from previous studies 16, xT. E and F show behavior of 43 deafferented units in the recovery stage. Note the presence of the 3 distributions (types I-III) which were estimated statistically by a 95 % density contour ellipse and a linear regression line throughout the 3 different experimental stages. In E, 16 units which discharged faster in R A than LS showed only one type of distribution (type I). F comprised 27 units which discharged faster in LS than RA. Two separate groupings were noted. One was almost superimposable on the distribution seen in E (an ellipse with dotted line in F is identical to that in E). The other had a quite different correlation function. Two of 8 points (i and k) which fell in the transition zone of both ellipses were determined finally to belong to the former (type II), based on comparison of the probability of belonging to either groupings. Remaining 6 points (f-h, j,1 and m) were grouped with the latter (type Ill). Number of units (N), correlation coefficient (C~)and regression coefficient (r) were shown for each type of distribution in each diagram.
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Fig. 4. Mean discharge rates (per sec) of deafferented visual cortical units in recovering stage on a logarithmic scale. All 43 units were observed throughout 3 states, i.e., resting arousal (RA), light sleep (LS) and deep sleep (DS). A: for 15 units which showed the highest rate in DS: 10 units (solid lines) increased the mean rate in a sequence LS < RA < DS; remaining 5 units (dotted lines) fell in a sequence RA < LS < DS. B: for 6 units with the highest rate in RA: mean rate shifted in sequences either LS < DS < RA (3 units, solid lines) or DS < LS < RA (3 units, dotted lines). C: for 22 units with the highest rate in LS: 14 units showed increasing rates in the gradation DS < RA < LS (solid lines) and 8 units had a gradation RA < DS < LS (dotted lines). Mean rate (MEAN) and standard deviation (S.D.) in each state are shown at the bottom of the 3 axes.
observed variety in correlation functions indicates the presence o f different neuron groups with different local neural networks. The behavior o f 43 units in the recovery stage is shown in Fig. 3E and F on the same type o f plot as for control records in Fig. 3A and B, and for records i m m e d i ately after enucleation (Fig. 3C and D). D a t a for control and enucleated plots are f r o m our previous studies16,17. Even though parameters which characterize these correlation functions in the recovery stage differed f r o m those in control records and immediately after enucleation, 3 similar groups o f units were still present in the recovery stage. In comparing the recovery records with control and enucleated data in Fig. 3, three points emerge. I m m e d i a t e l y after enucleation type III units (D) were predominant, whereas type I units prevailed in controls (A). First, the incidence o f types I and III units in the recovery stage (E and F) fell between numbers in control and enucleated stages. Reduction in the proportion o f type III units f r o m enucleated (32 o f 68 units) to recovery stages (11 o f 43 units) was statistically significant (Z z test, P < 0.05). The expected increase in type I units in the recovery stage was n o t obvious. The proportion o f type I units (16 o f 43 units) was still far less than in controls (46 o f 77 units).
DEAFFERENTED CORTICAL NEURONS
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Secondly, it is noteworthy, nevertheless, that the regression coefficient for type I units in the recovery stage (1.050, E) was very close to that in control records (1.009, A), and differed from that in the enucleated stage (1.348, C) which was quite close to that for type III units in controls (1.620, B). Third, the regression slope for type II units was little changed throughout the 3 stages (0.934 in B, 1.055 in D and 1.135 in F) but decreased systematically for type III units from the control level through the enucleated stage to the recovery level. All 6 possible patterns of gradation in discharge rate were observed between the 3 states. Fig. 4 was constructed for the same 43 units in the recovery stage shown in Fig. 3E and F. Fig. 4A comprises 15 units with highest activity in DS. Fig. 4C includes 22 units with highest activity in LS. Six units showed highest activity in RA (Fig. 4B). In comparing these diagrams with those in controls and immediately after enucleation 3 points characterized the recovery stage as intermediate between the control stage and immediately after enucleation. First, the proportion of units which increased their discharge rates in a sequence DS < RA < LS (Fig. 4C, solid lines) remained highest among the 6 possible patterns (14 of 43 units). This was smaller than the value immediately after enucleation (34 of 72 units) but was larger than in controls (9 of 79 units) (Zz test, P < 0.005). VC units with this gradation pattern in mean discharge rate were encountered throughout the 6 cortical layers in the recovery stage as was also the case immediately after enucleation. Secondly, the proportion of units with converse behavior, i.e., increased firing in a sequence LS < RA < DS (Fig. 4A, solid lines) was 23.3 ~o (10 of 43 units) in the recovery stage. This was slightly larger than immediately after enucleation (15 of 72 units, 20.8 ~ ) though it was still far smaller than in controls (35 of 79 units, 44.3 ~). Thirdly, the sampling incidence during recovery for units with the highest activity in RA (Fig. 4B) did not differ markedly from their occurrence in controls and immediately after enucleation. The average discharge rate for this group was intermediate between rates in Fig. 4A and C, irrespective of vigilance levels.
(3) Evoked units activity In the intact VC, it was demonstrated that gradation of unit responsiveness to afferent synchronous volleys paralleled the mean discharge rate 16. This parallel was also noted for deafferented units immediately after enucleation 17 and in the recovery stage. However, the proportion of units with different gradation patterns of unit responsiveness in the recovery stage was closer to that in controls than immediately after enucleation. Units with highest responsiveness in LS, lowest in DS and intermediate in RA were not the most common type in the recovery stage (3 of 21 units, Fig. 5A), although this type of unit was predominant immediately after enucleation (9 of 12 units). This incidence in the recovery stage resembled that in controls (2 of 15 units). A majority of units studied in the recovery stage showed highest responsiveness in DS (14 of 21 units, Fig. 5B and C). The most common type increased responsiveness in the sequence RA < LS < DS as seen in Fig. 5C. This type formed the second commonest group in controls (4 of 15 units).
112
T. KASAMATSU AND W. R. ADEY
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Fig. 5. Sample records of evoked unit activity in response to geniculate stimulation in the deafferented visual cortex in the recovery stage. Three behavioral states were classed: resting arousal (RA), light sleep (LS) and deep sleep (DS) from left to right. Positivity, upward. The repetition rate of successive sweeps was once every 1.3 sec. Time mark, 2 msec (A and B) and 1 msec (C). A: an example from the third largest group in the recovery stage (3 of 21 units). The gradation of unit responsiveness was in the order DS < R A < LS with increasing sensitivity. Note the presence of a small unit which behaved similarly. B: a unit in the second largest group (6 units) which increased unit responsiveness in the order LS < R A < DS. C: a pair of units in largest group (8 units) increased unit responsiveness in the sequence R A < LS < DS. The small unit in the negative-positive configuration had a shorter response latency than the large unit with the positive-negative form.
Our previous study showed that following visual deafferentation, correlations were lost between mean discharge rate and response latency to geniculate stimulation due to drop out of short-latency units ( < 2 msec) 17. A similar correlation was therefore sought for 32 units in the recovery stage. Although half the units were distributed close to the regression line and were located within the 95 ~ density contour ellipse which estimated the two-dimensional distribution statistically obtained for control units, no meaningful correlation could be found between these two measures for the sampled population as a whole. This was again due to lack of short-latency units ( < 2 msec), and also to an enhanced proportion of units with moderate latency (3-5 msec) and widely varying mean discharge rates.
(4) Functions of PGO waves in deep sleep We have previously noted that total visual deafferentation brought about dramatic changes in the modulatory effect of PGO waves on unit activity in the VC tS. One of the most interesting changes was appearance of inhibitory interactions between single unit activity and PGO waves in the VC which was not observed in control records. Observations in the recovery stage revealed that units were still present with relations to PGO waves resembling those immediately after enucleation (Fig. 6). Several points characterized unit activity in the recovery stage as intermediate between control records and those immediately after enucleation.
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Fig. 6. Various temporal correlations between unit activity (Unit) and ponto-geniculo-occipital (PGO) waves in the visual cortex (VC) and the lateral geniculate body (LGB) in recovery stage. Some of PGO waves were dotted. Time mark, 5 sec. Type A: high correlation, excitatory. Three of 52 units studied started to fire in bursts immediately after the onset of PGO waves. Type B: moderate correlation, excitatory. Ten units increased discharge rate in association with PGO waves without timelocked relations to them. Type C: moderate correlation, inhibitory. A unit was found discharging more frequently in the lull of PGO waves. Type D: high correlation, inhibitory. A large unit exemplified a type which slowed firing immediately after the onset of PGO waves in the background EEG (identified as the wavy biphasic oscillation). Four units were of this type. Type E: non-related. For 34 of 52 units (65.4 %) there were no definite relations, either excitatory or inhibitory, between unit activity and PGO waves.
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First, it was noted that the proportion of units in which firing slowed during PGO waves (5 of 52 units, Fig. 6C and D) tended to be smaller in the recovery stage than immediately after enucleation (17 of 84 units, in Fig. 2C and D of the preceding paper 18) (g 2 test, P < 0.085). Second, because of the relative increase in PGO-nonrelated units (34 units, Fig. 6E) in the recovery stage from those seen immediately after enucleation (42 units), the proportion of units responding with enhanced firing (13 units, Fig. 6 A and B) also decreased slightly in the recovery stage from that immediately after enucleation. Further evidence of recovery from effects of enucleation was found in comparison of laminar distribution of units at various depth in striate and nonstriate cortical areas. Most deafferented units in the recovery stage were recorded either in layer IV (21 of 41 striate units) or in layer III (5 of 11 nonstriate units) as was the case in controls and immediately after enucleation. Apart from this sampling difference between the cortical laminae, the majority of nonstriate units in the intact VC had certain positive correlates with PGO waves, but not more than half the sampled striate units showed these relations with PGO waves 15. Furthermore, these differences in the proportion of PGO-related units became statistically insignificant immediately after enucleation even though the proportion in the nonstriate area (t0 of 18 units) was slightly larger than in the striate area (32 of 66 units) ~8. The present study showed that the disappearance of this regional difference immediately after enucleation was temporary and that the original pattern was re-emerging at the time we designated as the recovery stage. A majority of striate units had no correlation with PGO waves (29 of 41 units) while more than half the nonstriate units showed certain correlates with PGO waves (6 of 11 units) (Z2 test, P <~ 0.12). The proportion of units with enhanced activity in association with PGO waves (including types A and B in Fig. 6) also tended to be larger in the nonstriate area (5 of 11 units) than in striate cortex (8 of 41 units) (Z2 test, P < 0.089). DISCUSSION
The present study demonstrated that a deafferented VC neuron population maintained an ability to restore certain characteristics of spontaneous discharge patterns, unit responsiveness to afferent synchronous volleys and responses accompanying PGO waves in DS. After an interval, the significant changes following total visual deafferentation subsided and were replaced by a general trend toward recovery of original features in controls. A similar recovery or compensatory process was previously reported in postdeafferentation enhancement of VC evoked potentials 19, and also in changes of maintained unit activity in the mesencephalic reticular formation in chronically blinded cats 14. On the other hand, among several indices used in the present study to trace long-term changes following blinding, only a measure which concerned the geniculocortical radiation fibers rather than cortical neurons themselves, failed to show signs o f recovery. Following deafferentation, a significant correlation between the response latency to geniculate stimulation and the maintained discharge rate established for
DEAFFERENTED CORTICAL NEURONS
115
some intact VC neurons was lost, through disappearance of units with short-latency responses. This persisted unchanged throughout later observations in the recovery stage. There are two other lines of evidence which would support this finding. First, Sakakura and Iwama 27 studied effects of bilateral eye enucleation on spontaneous and evoked unit activity in the LGB of adult cats and were unable to detect any notable differences a month later from those seen immediately after enucleation. They found that both the mean and distribution range for maintained discharge rates in LGB relay neurons were definitely smaller after deafferentation than before. Second, it appears that a specific type o f LGB unit may cease to function following deafferentation. Recently, Sherman e t al. 28 reported a marked reduction in the sampling incidence of Y-cells in the LGB of visually deprived young cats. These cells send fast conduction velocity fibers to the VC. Though visual afferent inputs to high visual centers were eliminated by quite different ways in the two studies referred to, both results suggest strongly that at least one type o f neuron in the LGB is heavily dependent on visual afferent inputs and highly susceptible to their withdrawal. It appears that this holds also for VC neurons. Recent neurophysiological studies in the visual system support the view that there are different groups of cells at each level of the visual pathway and that specific cell types at each level are connected to each other by specific fiber types in terms of their conduction velocityl~, 80. Granted that there is a gradual mobilization of reorganizing or recovery processes in the deafferented VC, how could this be achieved ? Previous authors noted that tetanization of the optic tract served to suppress the postdeafferentation potentiation o f VC evoked potentials in blinded monkeys and cats before degeneration of optic nerve terminals was complete 10. Under natural conditions, however, as noted previously the relatively silent optic radiation fibers in chronically blinded preparations do not bear a flood of impulses as in normal preparations19, 27. Mesencephalic or thalamic reticular neurons represent a major source of nonspecific inputs to the VC~,S,~, 29. The former exhibited significant dysfunction immediately after enucleation and showed signs of slow recovery about a month later 14. The maintained activity of the latter also appeared to decrease after enucleation 24. Therefore, it seems reasonable to look for additional or compensatory inputs to visually deafferented VC neurons from sources within the VC which might compensate for lack of specific inputs essential for normal operation o f neural circuits in the VC. It has been suggested that the impairment o f a sensory channel forces the animal to use and depend on other sensory modalities resulting in a greater development in the corresponding cerebral cortex both morphologically and chemically 4. However, it was not previously known that inflow from peripheral and central sources serving other sensory modalities increases in the visually deafferented VC. A probable explanation may lie in anatomical studies which suggested that in the CNS active afferent terminals are able to take over degenerating neighboring synaptic sites to establish new contacts at the expense of their previous specificity23,26. If this is only one important factor at degenerating terminals in the VC, the mode of reorganization would largely depend on the local microenvironment and would be expected to duplicate synaptic contacts that had remained active. However, as the
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p r e s e n t physiological a n d previous long-term a n a t o m i c a l o b s e r v a t i o n s by the L u n d s 23 showed, characteristics o f the deafferented n e u r o n p o p u l a t i o n c a m e to resemble closely, but n o t completely, those o f intact neurons. This m a y m e a n t h a t in a d d i t i o n to the general t r o p h i c influence o f degenerating p r e s y n a p t i c t e r m i n a l s on n e i g h b o r i n g active ones as suggested by R a i s m a n 26, there are also certain p r e d e t e r m i n e d o r quite selective mechanisms set in action in a d u l t m a m m a l s to minimize the d i s o r g a n i z a t i o n o f neural n e t w o r k s following deafferentation. F u r t h e r m o r e , the a b o v e hypothesis might help us in at least a p a r t i a l u n d e r s t a n d ing o f why previous a u t h o r s were unable to o b t a i n clearly positive results on effects o f visual d e p r i v a t i o n in a d u l t cats. T h e y n o t e d the severely limited recovery, behavioral a n d physiological, after visual d e p r i v a t i o n o f kittens in early life 31. Intrinsic selfpreservative mechanisms a p p e a r well established in the cortex o f a d u l t animals a n d are m a i n t a i n e d by the rich fabric o f neural contacts which r e m a i n active t h r o u g h cont i n u o u s excitation in the b a c k g r o u n d activity o f the system, irrespective o f the final f o r m o f these neural circuits established in the adult, which w o u l d largely d e p e n d on sensory experience in early life.
REFERENCES 1 AKIMOTO, H., UNO CREUTZFELDT, O., Reaktionen von Neuronen des optischen Cortex nach elektrischer Reizung unspezifischer Thalamuskerne, Arch. Psychiat. Nervenkr., 196 (1957/58) 494-519. 2 BAcH-Y-RITA, P., Neurophysiological basis of a tactile vision-substitution system, IEEE Trans. on man-machine systems, MMS, 11 (1970) 108-110. 3 BACH-Y-RITA, P., COLLINS,C.C., SAUNDERS,F. A., WHITE, B., AND SCADDEN,L., Vision substitution by tactile image projection, Nature (Lond.), 221 (1969) 963-964. 4 BENNETT,E., DIAMOND,M., KRECH,D., ANDROSENZWEIG,M., Chemical and anatomical plasticity of brain, Science, 146 (1964) 610-619. 5 BERGER, R., OLLEY, P., AND OSWALD, I., LEG and eye-movements and dreams of the blind, Electroenceph. clin. Neurophysiol., 13 (1961) 827. 6 BLANK, H. R., Dreams of the blind, Psychoanal. Quart., 27 (t958) 158-174. 7 COHEN,J., BOSHES,L. D., AND SNIDER, R. S., Electroencephalographicchanges following retrolental fibroplasia, Electroenceph. clin. Neurophysiol., 13 (1961) 914-922. 8 CREUTZFELDT,O., SPEHLMANN,R., UND LEHMANN,D., Ver~inderungen der Neuronaktivit~it des visuellen Cortex durch Reizung des Substantia reticularis mesencephali. In R. Jon6 UND H. KORNHUEER (Eds.), Neurophysiologie unclPsychophysik des visuellen Systems, Springer, Berlin, 1961, pp. 351-363. 9 DREVER, J., Some observations on the occipital alpha rhythm, Quart. J. exp. Psychol., 7 (1955) 91-97. 10 FENTRESS,J. C., AND DOTY, R. W., Effects of tetanization and enucleation upon excitability of visual pathways in squirrel monkeys and cats, Exp. Neurol., 30 (1971) 535-554. 11 FUSTER,J. M., Excitation and inhibition of neuronal firing in visual cortex by reticular stimulation, Science, 133 (1961) 2011-2012. 12 HOFFMANN, K.-P., AND STONE, J., Conduction velocity of afferents to cat visual cortex: a correlation with cortical receptive field properties, Brain Research, 32 (1971) 460466. 13 JEAVONS, P. M., The LEG in blind children, Brit. J. OphthaL, 48 (1964) 83-101. 14 KASAMATSU, T., Effects of visual deafferentation on mesencephalic reticular activity in freely behaving cats, Exp. NeuroL, 29 (1970) 251-267. 15 KASAMATSU,T., AND ADEY, W. R., Visual cortical units associated with phasic activity in REM sleep and wakefulness, Brain Research, 55 (1973) 323-331. 16 KASAMATSU,T., AND ADEY, W. R., Excitability changes in various types of visual cortical units in freely behaving cats, Physiol. Behav., (1974) in press.
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17 KASAMATSU,T., AND ADEY, W. R., Immediate effects of total visual deafferentation on single unit activity in the visual cortex of freely behaving cats I: Tonic excitability changes, Exp. Brain Res., (1974) in press. 18 KASAMATSU,T., AND ADEY, W. R., Immediate effects of total visual deafferentation on single unit activity in the visual cortex of freely behaving cats II: Rhythmic EEG bursts and PGO waves, Exp. Brain Res., (1974) in press. 19 KASAMATSU,T., K1YONO,S., AND IWAMA,K., Electrical activities of the visual cortex in chronically blinded cats, Tohoku J. exp. Med., 93 (1967) 139-152. 20 KELLAWAY,P., BLOXSOM,A., AND MACGREGOR,M., Occipital spike foci associated with retrolental fibroplasia and other forms of retinal loss in children, Electroenceph. din. Neurophysiok, 7 (1955) 469-470. 21 KRILL, A. E., AND STAMPS, F. W., The electroencephalogram in retinitis pigmentosa, Amer. J. Ophthal., 49 (1960) 762-773. 22 LENSe, I., EEG study in retinitis pigmentosa with a specific reference to the slow waves blocked by eye opening, Electroenceph. clin. NearophysioL, 13 (1961) 139. 23 LUND. R. D., AND LUND, J. S., Synaptic adjustment after deafferentation of the superior colliculus of the rat, Science, 171 (1971) 804-807. 24 MUKHAMETOV,L. M., RIZZOLATTI,G., AND TRADARDI,V., Spontaneous activity of neurones of nucleus reticularis thalami in freely moving cats, J. Physiol. (Lend.), 210 (1970) 651-667. 25 PAP,MELEE, A. H., JR., FISKE, C. E., AND WRIGHT, R. H., The development of ten children with blindness as a result of retrolental fibroplasia, Amer. J. Dis. Child., 98 (1959) 198-220. 26 RAISMAN,G., Neuronal plasticity in the septal nuclei of the adult rat, Brain Research, 14 (1969) 25-48. 27 SAKAI~tJRA,H., AND IWAMA, K., Effects of bilateral eye enucleation upon single unit activity of the lateral geniculate body in free behaving cats, Brain Research, 6 (1967) 667-678. 28 SHERMAN,S. M., HOFFMANN,K.-P., AND STONE, J., Loss of a specific cell type from dorsal lateral geniculate nucleus in visually deprived cats, J. Neurophysiol., 35 (1972) 532-541. 29 SKREBrrsKv, V. G., Nonspecific influences on neuronal firing in the central visual pathway, Exp. Brain Res., 9 (1969) 269-283. 30 STONE,J., AND DREHER, B., Projection of X- and Y-cell of the cat's lateral geniculate nucleus to area ' 17 and 18 of visual cortex, J. NeurophysioL, 36 (1973) 551-567. 31 WtESEL, T. N., AND HUa~L, D. H., Extent of recovery from the effects of visual deprivation in kittens, J. NeurophysioL, 28 (1965) 1060-1072.
© Elsevier Scientific Publishing Company, Amsterdam- Printed in The Netherlands
RECOVERY IN VISUAL CORTICAL VISUAL D E A F F E R E N T A T I O N
NEURONS
FOLLOWING
105
TOTAL
TAKUJI KASAMATSU* ANDW. ROSS ADEY Department of Anatomy and Brain Research Institute, University of California at Los Angeles, Los Angeles, Calif. 90024 (U.S.A.)
(Accepted January 10th, 1974)
SUMMARY Long-term effects of total visual deafferentation on the functional organization of the visual cortex were studied in freely behaving adult cats. Single unit activity in control records was compared with findings immediately after bilateral enucleation and after one month. Neuronal activity one month after enucleation was intermediate between control records and those immediately after enucleation, as revealed in the pattern and rate in maintained unit activity, unit responsiveness to geniculate stimulation, and in firing correlates of ponto-geniculo-occipital waves. The results suggest restoration of some basic cortical organizations in terms of neural excitability changes in shifting states o f vigilance.
INTRODUCTION Clinical E E G studies have described abnormal electrical activity in both the congenitally blind and subjects blinded after birth. The abnormality most frequently reported was paroxysmal EEG activity in the occipital area 7,20,25. Substantial reduction in occipital alpha rhythm has also been observedT,9,13. Nevertheless, except in cases ofretinitis pigmentosa, for example, where other forms of congenital defect are common 21,2z, these blinded subjects appear to have normal brain functions apart from the defect in visual perception. On the other hand, it has been reported that subjects blinded in later life tend to retain visual dream imagery with accompanying REMs, while the congenitally blind and those blinded in early life do not have either visual * Present address: Max-Planck-Institut fiir biophysikalische Chemie, D-3400 G6ttingen-Niko lausberg Postfach 968, G.F.R.
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dreams or REMs, and the predominant sensory modality in their dreams is auditory 5,6. Recently a unique approach has demonstrated that blind subjects may have a substitute for spatial perception through visual inputs including an experience equivalent to the visuomotor senseZ, 3. In these studies tactile receptors on the skin of the back substituted for visual afferents. The visual information from a TV camera is conveyed to the CNS through tactile receptors. A basic assumption in explaining this ability is that the deafferented visual cortex itself still maintains, at least in part, the original neuronal networks responsible for visual sensation. It was previously suggested that in chronically blinded adult cats some compensatory or recovery process partly restored some basic neural organization in the visual cortex to offset an initial dysfunction following total visual deafferentation 19. It was also shown that neural activity in nonspecific sensory neurons of the mesencephalic reticular formation decreased immediately after total visual deafferentation but tended later to recover its original level 14. This report provides further data in support of the proposed possibility of reorganization of visual cortical neuron nets with respect to maintained and evoked single unit activity recorded in cats without visual inputs. Records were obtained from each animal first with the intact visual cortex, then immediately after the complete elimination of visual inputs, and finally 1 month after surgery. Some characteristics of visual cortical neurons which we may attribute to intracortical neural circuits showed definite trends toward restoration of original features but others involving the geniculocortical radiations did not. Results 1 month after enucleation are referred to as 'recovery' and those immediately after surgery as 'enucleated'. METHODS
Four adult cats were used. Bipolar electrodes were implanted under general anesthesia in the left sensorimotor cortex (SMC), the left visual cortex (VC) and the right lateral geniculate body (LGB). These electrodes monitored background EEGs. In order to hold a hydraulic microdrive a metal pedestal was also placed above the posterolateral gyrus in the right occipital area (its center located at AP, - - 2 to - - 4 mm; ML, 2 - 4 ram). In the present experiment recordings were made 30-41 days after surgical removal o f the eyes under barbiturate anesthesia. The animals received an injection of Bicillin (600,000 units) every other day for a week postoperatively. Tungsten microelectrodes insulated with Araldite 985E (Ciba) were used. At the conclusion of the experiment the animals were sacrificed under barbiturate anesthesia. The brains were fixed in 1 0 ~ formalin. Microelectrode tracks were reconstructed from serial histological sections 10/~m thick on the basis of both mierodrive readings and microlesions made at the lowest points of each penetration. The animal was kept in a dim-lit observation box during each recording session which lasted usually for several hours. They were unrestrained and able to move freely. Recording conditions were classed in 3 states described previously15-lv: (1) resting arousal (RA) with desynchronized EEG in the SMC. The cat sat or crouched quietly without vigorous body movements; (2) light sleep (LS) with high-amplitude synchronized cortical EEGs;
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Fig. 1. Three sample records of unit discharges (Unit) in the visually deafferented visual cortex in resting arousal. Unit records were obtained a month after bilateral eye enucleation, concurrently with EEGs from the contralateral visual cortex (VC) and the ipsilateral lateral geniculate body (LGB).
A: the unit tended to fire phasically in association with rhythmic slow wave bursts in the VC. B: the sustained discharge was blocked in association with rhythmic slow wave bursts in the VC. Note the trend for a short-burst firing pattern• C: no definite relation between unit firing and the EEG pattern in the VC. Time mark, 5 sec. (3) deep sleep (DS or REM) with desynchronized cortical EEGs and silent cervical E M G . Ponto-geniculo-occipital (PGO) waves were observed in the LGB and the VC. Details of experimental techniques were presented elsewhere 1~-1s. RESULTS
(1) Discharge pattern characteristics Our previous studies described characteristic changes in unit discharge patterns in the VC immediately after total visual deafferentation17,18. The visual cortical E E G during R A showed rhythmic synchronous slow wave bursts in an otherwise desynchronized record. These bursts were still observed 1 month after enucleation. However, the proportion of units which correlated with rhythmic slow wave bursts was lowered after 1 month, suggesting a decline in this hypersynchronous trend in the deafferented VC. In Fig. 1, 3 different correlates with slow E E G waves are shown, as with units tested immediately after enucleation. As exemplified in A and B, single unit activity had either an excitatory ( n = 4 units) or an inhibitory (n----3 units) relation with rhythmic slow wave bursts in the background. As seen in Fig. 1C, however, a majority o f
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deafferented units (24 o f 31 units) showed no definite correlation with rhythmic slow wave bursts. The proportion of non-related units in the recovery stage was significantly larger than in the enucleated stage (46 o f 97 units) (Z2 test, P < 0.01). This restorative feature in discharge patterns 1 month after deafferentation was also noted in the coefficient o f variation o f interspike intervals. Fig. 2 shows how the coefficient o f variation in unit discharge intervals fluctuates in the 3 behavioral states throughout the 3 experimental stages. As mentioned previously 17, no significant difference was noted in the overall mean interspike interval before and after enucleation. However, when we compare measures obtained in the same behavioral states during the 3 experimental stages, the coefficient o f variation o f discharge intervals tended to larger values immediately after enucleation and became smaller again in the recovery stage irrespective o f vigilance levels.
(2) Sampling incidence of the three types of VC units The 3 different types o f units were noted previously in the intact in and the deafferented VC 17 according to the correlation function between mean discharge rates in R A and changes in rate with shifts into LS. The correlation function was introduced to evaluate quantitatively, on the basis o f mean discharge rate o f individual neurons, the average responsiveness o f a neuron population to tonic central influences which determined the direction and the amount o f excitability changes o f individual neurons in shifting vigilance levels. Assumed that excitation or inhibition maintained by these tonic central mechanisms works on each cortical neuron in a similar way, the
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Fig. 4. Mean discharge rates (per sec) of deafferented visual cortical units in recovering stage on a logarithmic scale. All 43 units were observed throughout 3 states, i.e., resting arousal (RA), light sleep (LS) and deep sleep (DS). A: for 15 units which showed the highest rate in DS: 10 units (solid lines) increased the mean rate in a sequence LS < RA < DS; remaining 5 units (dotted lines) fell in a sequence RA < LS < DS. B: for 6 units with the highest rate in RA: mean rate shifted in sequences either LS < DS < RA (3 units, solid lines) or DS < LS < RA (3 units, dotted lines). C: for 22 units with the highest rate in LS: 14 units showed increasing rates in the gradation DS < RA < LS (solid lines) and 8 units had a gradation RA < DS < LS (dotted lines). Mean rate (MEAN) and standard deviation (S.D.) in each state are shown at the bottom of the 3 axes.
observed variety in correlation functions indicates the presence o f different neuron groups with different local neural networks. The behavior o f 43 units in the recovery stage is shown in Fig. 3E and F on the same type o f plot as for control records in Fig. 3A and B, and for records i m m e d i ately after enucleation (Fig. 3C and D). D a t a for control and enucleated plots are f r o m our previous studies16,17. Even though parameters which characterize these correlation functions in the recovery stage differed f r o m those in control records and immediately after enucleation, 3 similar groups o f units were still present in the recovery stage. In comparing the recovery records with control and enucleated data in Fig. 3, three points emerge. I m m e d i a t e l y after enucleation type III units (D) were predominant, whereas type I units prevailed in controls (A). First, the incidence o f types I and III units in the recovery stage (E and F) fell between numbers in control and enucleated stages. Reduction in the proportion o f type III units f r o m enucleated (32 o f 68 units) to recovery stages (11 o f 43 units) was statistically significant (Z z test, P < 0.05). The expected increase in type I units in the recovery stage was n o t obvious. The proportion o f type I units (16 o f 43 units) was still far less than in controls (46 o f 77 units).
DEAFFERENTED CORTICAL NEURONS
111
Secondly, it is noteworthy, nevertheless, that the regression coefficient for type I units in the recovery stage (1.050, E) was very close to that in control records (1.009, A), and differed from that in the enucleated stage (1.348, C) which was quite close to that for type III units in controls (1.620, B). Third, the regression slope for type II units was little changed throughout the 3 stages (0.934 in B, 1.055 in D and 1.135 in F) but decreased systematically for type III units from the control level through the enucleated stage to the recovery level. All 6 possible patterns of gradation in discharge rate were observed between the 3 states. Fig. 4 was constructed for the same 43 units in the recovery stage shown in Fig. 3E and F. Fig. 4A comprises 15 units with highest activity in DS. Fig. 4C includes 22 units with highest activity in LS. Six units showed highest activity in RA (Fig. 4B). In comparing these diagrams with those in controls and immediately after enucleation 3 points characterized the recovery stage as intermediate between the control stage and immediately after enucleation. First, the proportion of units which increased their discharge rates in a sequence DS < RA < LS (Fig. 4C, solid lines) remained highest among the 6 possible patterns (14 of 43 units). This was smaller than the value immediately after enucleation (34 of 72 units) but was larger than in controls (9 of 79 units) (Zz test, P < 0.005). VC units with this gradation pattern in mean discharge rate were encountered throughout the 6 cortical layers in the recovery stage as was also the case immediately after enucleation. Secondly, the proportion of units with converse behavior, i.e., increased firing in a sequence LS < RA < DS (Fig. 4A, solid lines) was 23.3 ~o (10 of 43 units) in the recovery stage. This was slightly larger than immediately after enucleation (15 of 72 units, 20.8 ~ ) though it was still far smaller than in controls (35 of 79 units, 44.3 ~). Thirdly, the sampling incidence during recovery for units with the highest activity in RA (Fig. 4B) did not differ markedly from their occurrence in controls and immediately after enucleation. The average discharge rate for this group was intermediate between rates in Fig. 4A and C, irrespective of vigilance levels.
(3) Evoked units activity In the intact VC, it was demonstrated that gradation of unit responsiveness to afferent synchronous volleys paralleled the mean discharge rate 16. This parallel was also noted for deafferented units immediately after enucleation 17 and in the recovery stage. However, the proportion of units with different gradation patterns of unit responsiveness in the recovery stage was closer to that in controls than immediately after enucleation. Units with highest responsiveness in LS, lowest in DS and intermediate in RA were not the most common type in the recovery stage (3 of 21 units, Fig. 5A), although this type of unit was predominant immediately after enucleation (9 of 12 units). This incidence in the recovery stage resembled that in controls (2 of 15 units). A majority of units studied in the recovery stage showed highest responsiveness in DS (14 of 21 units, Fig. 5B and C). The most common type increased responsiveness in the sequence RA < LS < DS as seen in Fig. 5C. This type formed the second commonest group in controls (4 of 15 units).
112
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Our previous study showed that following visual deafferentation, correlations were lost between mean discharge rate and response latency to geniculate stimulation due to drop out of short-latency units ( < 2 msec) 17. A similar correlation was therefore sought for 32 units in the recovery stage. Although half the units were distributed close to the regression line and were located within the 95 ~ density contour ellipse which estimated the two-dimensional distribution statistically obtained for control units, no meaningful correlation could be found between these two measures for the sampled population as a whole. This was again due to lack of short-latency units ( < 2 msec), and also to an enhanced proportion of units with moderate latency (3-5 msec) and widely varying mean discharge rates.
(4) Functions of PGO waves in deep sleep We have previously noted that total visual deafferentation brought about dramatic changes in the modulatory effect of PGO waves on unit activity in the VC tS. One of the most interesting changes was appearance of inhibitory interactions between single unit activity and PGO waves in the VC which was not observed in control records. Observations in the recovery stage revealed that units were still present with relations to PGO waves resembling those immediately after enucleation (Fig. 6). Several points characterized unit activity in the recovery stage as intermediate between control records and those immediately after enucleation.
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Fig. 6. Various temporal correlations between unit activity (Unit) and ponto-geniculo-occipital (PGO) waves in the visual cortex (VC) and the lateral geniculate body (LGB) in recovery stage. Some of PGO waves were dotted. Time mark, 5 sec. Type A: high correlation, excitatory. Three of 52 units studied started to fire in bursts immediately after the onset of PGO waves. Type B: moderate correlation, excitatory. Ten units increased discharge rate in association with PGO waves without timelocked relations to them. Type C: moderate correlation, inhibitory. A unit was found discharging more frequently in the lull of PGO waves. Type D: high correlation, inhibitory. A large unit exemplified a type which slowed firing immediately after the onset of PGO waves in the background EEG (identified as the wavy biphasic oscillation). Four units were of this type. Type E: non-related. For 34 of 52 units (65.4 %) there were no definite relations, either excitatory or inhibitory, between unit activity and PGO waves.
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T. K A S A M A T S U A N D W . R. A D E Y
First, it was noted that the proportion of units in which firing slowed during PGO waves (5 of 52 units, Fig. 6C and D) tended to be smaller in the recovery stage than immediately after enucleation (17 of 84 units, in Fig. 2C and D of the preceding paper 18) (g 2 test, P < 0.085). Second, because of the relative increase in PGO-nonrelated units (34 units, Fig. 6E) in the recovery stage from those seen immediately after enucleation (42 units), the proportion of units responding with enhanced firing (13 units, Fig. 6 A and B) also decreased slightly in the recovery stage from that immediately after enucleation. Further evidence of recovery from effects of enucleation was found in comparison of laminar distribution of units at various depth in striate and nonstriate cortical areas. Most deafferented units in the recovery stage were recorded either in layer IV (21 of 41 striate units) or in layer III (5 of 11 nonstriate units) as was the case in controls and immediately after enucleation. Apart from this sampling difference between the cortical laminae, the majority of nonstriate units in the intact VC had certain positive correlates with PGO waves, but not more than half the sampled striate units showed these relations with PGO waves 15. Furthermore, these differences in the proportion of PGO-related units became statistically insignificant immediately after enucleation even though the proportion in the nonstriate area (t0 of 18 units) was slightly larger than in the striate area (32 of 66 units) ~8. The present study showed that the disappearance of this regional difference immediately after enucleation was temporary and that the original pattern was re-emerging at the time we designated as the recovery stage. A majority of striate units had no correlation with PGO waves (29 of 41 units) while more than half the nonstriate units showed certain correlates with PGO waves (6 of 11 units) (Z2 test, P <~ 0.12). The proportion of units with enhanced activity in association with PGO waves (including types A and B in Fig. 6) also tended to be larger in the nonstriate area (5 of 11 units) than in striate cortex (8 of 41 units) (Z2 test, P < 0.089). DISCUSSION
The present study demonstrated that a deafferented VC neuron population maintained an ability to restore certain characteristics of spontaneous discharge patterns, unit responsiveness to afferent synchronous volleys and responses accompanying PGO waves in DS. After an interval, the significant changes following total visual deafferentation subsided and were replaced by a general trend toward recovery of original features in controls. A similar recovery or compensatory process was previously reported in postdeafferentation enhancement of VC evoked potentials 19, and also in changes of maintained unit activity in the mesencephalic reticular formation in chronically blinded cats 14. On the other hand, among several indices used in the present study to trace long-term changes following blinding, only a measure which concerned the geniculocortical radiation fibers rather than cortical neurons themselves, failed to show signs o f recovery. Following deafferentation, a significant correlation between the response latency to geniculate stimulation and the maintained discharge rate established for
DEAFFERENTED CORTICAL NEURONS
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some intact VC neurons was lost, through disappearance of units with short-latency responses. This persisted unchanged throughout later observations in the recovery stage. There are two other lines of evidence which would support this finding. First, Sakakura and Iwama 27 studied effects of bilateral eye enucleation on spontaneous and evoked unit activity in the LGB of adult cats and were unable to detect any notable differences a month later from those seen immediately after enucleation. They found that both the mean and distribution range for maintained discharge rates in LGB relay neurons were definitely smaller after deafferentation than before. Second, it appears that a specific type o f LGB unit may cease to function following deafferentation. Recently, Sherman e t al. 28 reported a marked reduction in the sampling incidence of Y-cells in the LGB of visually deprived young cats. These cells send fast conduction velocity fibers to the VC. Though visual afferent inputs to high visual centers were eliminated by quite different ways in the two studies referred to, both results suggest strongly that at least one type o f neuron in the LGB is heavily dependent on visual afferent inputs and highly susceptible to their withdrawal. It appears that this holds also for VC neurons. Recent neurophysiological studies in the visual system support the view that there are different groups of cells at each level of the visual pathway and that specific cell types at each level are connected to each other by specific fiber types in terms of their conduction velocityl~, 80. Granted that there is a gradual mobilization of reorganizing or recovery processes in the deafferented VC, how could this be achieved ? Previous authors noted that tetanization of the optic tract served to suppress the postdeafferentation potentiation o f VC evoked potentials in blinded monkeys and cats before degeneration of optic nerve terminals was complete 10. Under natural conditions, however, as noted previously the relatively silent optic radiation fibers in chronically blinded preparations do not bear a flood of impulses as in normal preparations19, 27. Mesencephalic or thalamic reticular neurons represent a major source of nonspecific inputs to the VC~,S,~, 29. The former exhibited significant dysfunction immediately after enucleation and showed signs of slow recovery about a month later 14. The maintained activity of the latter also appeared to decrease after enucleation 24. Therefore, it seems reasonable to look for additional or compensatory inputs to visually deafferented VC neurons from sources within the VC which might compensate for lack of specific inputs essential for normal operation o f neural circuits in the VC. It has been suggested that the impairment o f a sensory channel forces the animal to use and depend on other sensory modalities resulting in a greater development in the corresponding cerebral cortex both morphologically and chemically 4. However, it was not previously known that inflow from peripheral and central sources serving other sensory modalities increases in the visually deafferented VC. A probable explanation may lie in anatomical studies which suggested that in the CNS active afferent terminals are able to take over degenerating neighboring synaptic sites to establish new contacts at the expense of their previous specificity23,26. If this is only one important factor at degenerating terminals in the VC, the mode of reorganization would largely depend on the local microenvironment and would be expected to duplicate synaptic contacts that had remained active. However, as the
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T. KASAMATSU A N D W . R. ADEY
p r e s e n t physiological a n d previous long-term a n a t o m i c a l o b s e r v a t i o n s by the L u n d s 23 showed, characteristics o f the deafferented n e u r o n p o p u l a t i o n c a m e to resemble closely, but n o t completely, those o f intact neurons. This m a y m e a n t h a t in a d d i t i o n to the general t r o p h i c influence o f degenerating p r e s y n a p t i c t e r m i n a l s on n e i g h b o r i n g active ones as suggested by R a i s m a n 26, there are also certain p r e d e t e r m i n e d o r quite selective mechanisms set in action in a d u l t m a m m a l s to minimize the d i s o r g a n i z a t i o n o f neural n e t w o r k s following deafferentation. F u r t h e r m o r e , the a b o v e hypothesis might help us in at least a p a r t i a l u n d e r s t a n d ing o f why previous a u t h o r s were unable to o b t a i n clearly positive results on effects o f visual d e p r i v a t i o n in a d u l t cats. T h e y n o t e d the severely limited recovery, behavioral a n d physiological, after visual d e p r i v a t i o n o f kittens in early life 31. Intrinsic selfpreservative mechanisms a p p e a r well established in the cortex o f a d u l t animals a n d are m a i n t a i n e d by the rich fabric o f neural contacts which r e m a i n active t h r o u g h cont i n u o u s excitation in the b a c k g r o u n d activity o f the system, irrespective o f the final f o r m o f these neural circuits established in the adult, which w o u l d largely d e p e n d on sensory experience in early life.
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17 KASAMATSU,T., AND ADEY, W. R., Immediate effects of total visual deafferentation on single unit activity in the visual cortex of freely behaving cats I: Tonic excitability changes, Exp. Brain Res., (1974) in press. 18 KASAMATSU,T., AND ADEY, W. R., Immediate effects of total visual deafferentation on single unit activity in the visual cortex of freely behaving cats II: Rhythmic EEG bursts and PGO waves, Exp. Brain Res., (1974) in press. 19 KASAMATSU,T., K1YONO,S., AND IWAMA,K., Electrical activities of the visual cortex in chronically blinded cats, Tohoku J. exp. Med., 93 (1967) 139-152. 20 KELLAWAY,P., BLOXSOM,A., AND MACGREGOR,M., Occipital spike foci associated with retrolental fibroplasia and other forms of retinal loss in children, Electroenceph. din. Neurophysiok, 7 (1955) 469-470. 21 KRILL, A. E., AND STAMPS, F. W., The electroencephalogram in retinitis pigmentosa, Amer. J. Ophthal., 49 (1960) 762-773. 22 LENSe, I., EEG study in retinitis pigmentosa with a specific reference to the slow waves blocked by eye opening, Electroenceph. clin. NearophysioL, 13 (1961) 139. 23 LUND. R. D., AND LUND, J. S., Synaptic adjustment after deafferentation of the superior colliculus of the rat, Science, 171 (1971) 804-807. 24 MUKHAMETOV,L. M., RIZZOLATTI,G., AND TRADARDI,V., Spontaneous activity of neurones of nucleus reticularis thalami in freely moving cats, J. Physiol. (Lend.), 210 (1970) 651-667. 25 PAP,MELEE, A. H., JR., FISKE, C. E., AND WRIGHT, R. H., The development of ten children with blindness as a result of retrolental fibroplasia, Amer. J. Dis. Child., 98 (1959) 198-220. 26 RAISMAN,G., Neuronal plasticity in the septal nuclei of the adult rat, Brain Research, 14 (1969) 25-48. 27 SAKAI~tJRA,H., AND IWAMA, K., Effects of bilateral eye enucleation upon single unit activity of the lateral geniculate body in free behaving cats, Brain Research, 6 (1967) 667-678. 28 SHERMAN,S. M., HOFFMANN,K.-P., AND STONE, J., Loss of a specific cell type from dorsal lateral geniculate nucleus in visually deprived cats, J. Neurophysiol., 35 (1972) 532-541. 29 SKREBrrsKv, V. G., Nonspecific influences on neuronal firing in the central visual pathway, Exp. Brain Res., 9 (1969) 269-283. 30 STONE,J., AND DREHER, B., Projection of X- and Y-cell of the cat's lateral geniculate nucleus to area ' 17 and 18 of visual cortex, J. NeurophysioL, 36 (1973) 551-567. 31 WtESEL, T. N., AND HUa~L, D. H., Extent of recovery from the effects of visual deprivation in kittens, J. NeurophysioL, 28 (1965) 1060-1072.