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Biochemical plasticity in the superior colliculus of adult rats after chronic visual cortex ablation
Brain Research, 372 (1986) 189-192 Elsevier
189
BRE21528
Biochemical plasticity in the superior colliculus of adult rats after chronic visual cortex ablation VIGGO M. FOSSE and PER K. OPSTAD
Norwegian Defence Research Establishment, Division for Environmental Toxicology, N-2007 Kjeller (Norway) (Accepted January 14th, 1986)
Key words: visual cortex - - superior colliculus - - r~-Aspuptake - - glutamate decarboxylase - - noradrenaline - - plasticity - - rat
We have measured the changes of several neurochemical parameters in the adult rat superior colliculus (SC) 1.5-4 months after unilateral visual cortex ablation. High-affinity uptake of D-[3H]Aspwas increased by 22.5% and glutamate decarboxylase by 10% in the ipsilateral SC. This may be largely attributed to reactive synaptogenesis of intrinsic glutamatergic and GABAergic neurons, respectively. The noradrenaline content was increased by about 60 and 25% in the ipsi- and contralateral SCs, respectively. The latter probably reflects sprouting of noradrenergic fibres from the locus coeruleus.
Ablation of the visual cortex (VC) in adult rats brings forth a substantial increase in the number of noradrenaline (NA)-containing terminals in the lateral geniculate body (LGB) 25,31 as judged by histofluorescence. It is thought that this reflects plastic changes (sprouting) of ascending fibres from the locus coeruleus 25. Also, plastic changes with concomitant increased noradrenergic innervation has been demonstrated in the septal area after fimbria lesion 17 and in hippocampus after medial septal lesion in adult rats 14. Lesions have also been shown to provoke plastic changes in the superior colliculus (SC) 12'26 which were attributed to a 'pruning effect' of remaining axons. Previously, we have shown that VC ablation reduces high-affinity uptake of D-aspartate in SC by 30-35% in adult rats when measured one week postsurgery 7'z°'13. Thus, evidence has been obtained to suggest glutamate (and/or aspartate) as transmitter(s) of visual corticofugal afferents in SC. In addition, the SC harbors a considerable number of local (intrinsic) Glu-neurons 7 and G A B A neurons 16. Most likely, only a small fraction of the retinotectal fibres seem to employ Glu as their transmitter 7. In deafferented brain regions degeneration of
nerve terminals elicits hypertrophy, redistribution and some proliferation of astrocytes 3'23, which accumulate acidic amino acid neurotransmitters avidly ~,6. Moreover, in the hippocampus deafferentation provokes reactive synaptogenesis 3. In this study we have therefore investigated by biochemical methods to what extents catecholaminergic, glutamatergic, G A B A e r g i c and cholinergic parameters in the SC of adult rats were affected several months after VC ablation. This was done in order to monitor possible plastic changes in the SC after chronic deafferentation as judged by the biochemical criteria. Adult male Wistar rats, 160-180 g (M~llergaard Avlslaboratorium, Denmark) were employed. Surgical procedures and tissue preparation were similar to those described by Fosse and Fonnum 7, as were the methods to measure high-affinity uptake of D-[3H] aspartate (D-[3H]Asp), glutamate decarboxylase ( G A D ) , choline acetyltransferase (CHAT) and protein. Animals to be used for catecholamine (CA) analysis were killed by decapitation. The heads were chilled in liquid N2 and the visual part 8 of SC was dissected from 600-/~m-thick slices. The pia with adher-
Correspondence: V.M. Fosse. Present address: Norwegian Underwater Technology Center, P.O. Box 6, N-5034 Ytre Laksevfig, Bergen, Norway. 0006-8993/86/$03.50 © 1986 Elsevier Science Publishers B.V. (Biomedical Division)
190 TABLE I High-affinity uptake of o-[3H]Asp GAD and ChAT activities in the adult rat superior colliculus 3..5 months after unilateral visual cortex ablation.
Results are presented as nmol.g protein-l.h-~ for D-[3H]Asp and as/~mol.g protein-Lh -1 for GAD and CHAT. Values are means _+ S.E.M. Differences between non-operated (control) and operated (deafferented) sides: * P < 0.001 (Student's t-test). Activities in SC on the non-operated side did not differ significantly from those in the SC of non-operated animals of the same age. Control
D-[3H]Asp 525 _+ 19 GAD 245 + 3 ChAT 22.5_+ 0.8
Deafferented
% Change
n
644 __+16" 270 + 2* 23.1 + 0.4
+22.5 +10.1 + 3.2
11 6 6
ing vasculature and b l o o d were r e m o v e d from the tissue by immersion in ice-cold 0.32 M sucrose. Subsequently each slice (ca. 10 mg) was transferred to 1 m l ice-cold 0.2 M perchloric acid ( P C A ) , homogenized by hand in a glass-glass h o m o g e n i z e r and extracted for 15 rain on ice. C A concentrations in the extracts were d e t e r m i n e d by a radioenzymatic m e t h o d 4,2°. P o s t m o r t e m changes of C A s were not a p r o b l e m in this study in light of the relatively short time interval (i.e. less than 5 min) from decapitation to P C A - e x traction 24. In Table I is shown that 3.5 months after VC ablation D-[aH]Asp and G A D in h o m o g e n a t e s of the deafferented SC was increased by 22.5 and 10.9%, respectively, relative to the contralateral SC. The
TABLE II Effects of chronic VC ablation on content of NA and DA in the adult rat superior coUiculus
Results are presented as pmol/mg protein (mean + S.E.M.). Numbers in parentheses underneath the values are the % change relative to unoperated controls of the same age. Differences between operated and non-operated animals were: * P < 0.05, ** P < 0.001 and *** P < 0.0001 (Student's t-test).
NA
Time after lesion
Non-operated side
Operated side
n
- (control 1.5 months
22.3 _+0.6 26.9 _ 1.8" (+21%) 29.0 + 2.4* (+30%) 9.3 +_ 1.1 10.9 + 0.2 10.6 + 0.6
35.7 ___2.7** (+60%) 36.7 + 1.4"** (+65%) 11.6 +_0.3 10.8 + 0.7
6 6
4 months DA
- (control) 1.5 months 4 months
5 6 6 5
change in C h A T activity was only marginal and not statistically significant. In contrast, 6 months after unilateral enucleation D-[3H]Asp in the contralateral SC was reduced by 26% relative to the control SC. G A D was reduced by 10%, whereas C h A T was not affected (unpublished observation). The contents of N A and d o p a m i n e ( D A ) in the SC of n o n - o p e r a t e d adult rats were 22.3 and 9.3 p m o l ' g protein -1, respectively (Table II). The adrenaline content was 1.15 pmol/mg protein. Changes in the content of catecholamines were measured in the SC of adult rats at two time-points after unilateral VC ablation. The control values of n o n - o p e r a t e d adult rats were obtained from animals of the same age as those with chronic visual cortex ablations. In the ipsilateral SC N A was increased by 60% c o m p a r e d to the controls (Table II). In the contralateral SC N A was increased as well, but only by 2 0 - 3 0 % . The changes found after 1.5 months were retained or slightly increased 4 months postsurgery. In contrast, the D A content was not affected significantly by VC ablation (Table 1I), nor was the adrenaline content affected. In previous studies we have found that short-term (i.e. 1 week) VC ablation reduces D-[3H]Asp uptake in the ipsilaterai SC by 3 0 - 4 0 % 1(1'13, which was attributed to degeneration of glutamatergic corticofugal terminals 7. H e r e we find, however, that after long survival times homogenates of the deafferented SC accumulate D-[3H]Asp more avidly than the controls, i.e. non-deafferented SC. The reason for this is not immediately a p p a r e n t and may be the result of several factors. It is known from other visual areas that synaptic reorganization takes place after long-term deafferentation 26'2s'29. Most likely, dendritic sprouting of intrinsic neurons contribute in this process 5'28'29. The SC harbors intrinsic Glu and G A B A neurons 7'16'21 and possibly glutamatergic corticofugal afferents of extravisual origin 15. Sprouting of Gtu and G A B A terminals may contribute to the increased D-[3H]Asp uptake and G A D activities, respectively, after chronic decortication. Increased capacity for G A B A synthesis has been observed in deafferented hippocampus 19 which most likely reflects reactive synaptogenesis of intrinsic G A B A neurons 3. Thus, reactive synaptogenesis of intrinsic Glu and G A B A neurons may also take place in the SC after chronic deafferentation.
191 Shrinkage (i.e. atrophy) of the SC could also contribute to the o b s e r v e d increases of D-Jail]Asp uptake, G A D and N A . H o w e v e r , this is an unlikely explanation. Otherwise C h A T and D A would also be expected to increase. Conceivably, the increased D-[3H]Asp uptake could also be due to the presence of reactive astrocytes which proliferate and redistribute in the terminal area after deafferentation 23'31 and which have a high capacity for amino acid u p t a k e 1. H o w e v e r , the astrocytic reaction is an early response which occurs during the first two weeks after deafferentation 3"23. Most likely, they are not responsible for the increase in D-[aH]Asp uptake. R a t h e r , they may supply trophic factors which p r o m o t e terminal sprouting 3. The possibility that ingrowth of vascular sympathetic axons 2'11'3° and increased vascularization 25 contribute to increased D-[3H]Asp u p t a k e and N A content of the deafferented SC can not be entirely excluded. Since the D A and N A innervation of cerebral vessels is still elusive 27 it is at present difficult to discuss this point. The n o r a d r e n e r g i c p r o j e c t i o n from L C arises very early in development, and retains a m a r k e d propensity to form axon collaterals in response to cellular injury also in a d u l t h o o d TM. The L C afferents have a diffuse topographic distribution whereas the D A fibres a p p e a r m o r e topographically restricted and less responsive to injury TM, which c o r r o b o r a t e s our finding that only the N A system was affected in the rat SC after chronic VC ablation (Table II). Also, the per-
1 Balcar, V.J., Borg, J. and Mandel, P., High affinity uptake of L-glutamate and L-aspartate by glial cells, J. Neurochem., 28 (1977) 87-93. 2 Boast, C.A., Reid, S.A., Johnson, P. and Zornetzer, S.F., A caution to brain scientists: unsuspected hemorrhagic vascular damage resulting from more electrode implantation, Brain Research, 103 (1976) 527-534. 3 Cotman, C.W. and Nadler, J.V., Reactive synaptogenesis in the hippocampus. In C.W. Cotman (Ed.), Neuronal Plasticity, Raven, New York, (1978) pp. 227-271. 4 Da Prada, M. and Ziircher, G., Simultaneous radioenzymatic determination of plasma and tissue adrenalin, noradrenaline and dopamine within the femtomole range, Life Sci., t9 (1976) 1161-1174. 5 Eysel, U. Th., Functional reconnection without new axonal growth in a partially denervated visual relay nucleus, Nature (London), 299 (1982) 442-444. 6 Fonnum, F., Glutamate: a neurotransmitter in mammalian brain, J. Neurochem., 42 (1984) 1-11. 7 Fosse, V.M. and Fonnum, F., Effects of kainic acid, and
sistence of the increased N A content for several months after surgery c o r r o b o r a t e d previous observations in L G B 25. By the histofluorescence technique no increase in N A terminals was seen in the SC after VC ablation 31 although the visual part of SC receives a relatively dense noradrenergic innervation from the locus coeruleus TM. The increase in N A may, however, have been m a s k e d by the relatively intense fluorescence of the superficial SC 31 and the bilateral increase in N A content (Table II). M o r e o v e r , Stenevi et al. 31 did only examine the decorticated animals after short survival times, i.e. 2 - 4 weeks. As shown in Table II there was a small, but still significant, increase of N A in the contralateral non-deafferented SC, also. Similarly, sprouting of LC fibres have been observed in the contralateral L G B in response to the more extensive unilateral visual cortex lesions 25. As yet, we can not conclude that there was a direct causal relationship b e t w e e n the observed changes in the noradrenergic system of the adult rat SC and the increased D-[3H]Asp uptake and G A D activity after deafferentation. O u r d a t a do, however, provide biochemical evidence for long-term plastic changes in the rat SC after chronic visual cortex ablation which presumably reflects sprouting of intrinsic neurons and u n d a m a g e d afferents. The increased density of noradrenaline terminals p r o b a b l y serves to enhance activity of remaining intrinsic neurons, as has been d e m o n s t r a t e d in the L G B 9'22'25.
other excitotoxins, in the rat superior colliculus: relations to visual corticofugal afferents, Brain Research, submitted. 8 Fosse, V.M., Heggelund, P., Iversen, E. and Fonnum, F., Effects of Area 17 ablation on neurotransmitter parameters in efferents to Area 18, the lateral geniculate body, pulvinar and superior colliculus in the cat, Neurosci. Lett., 52 (1984) 323-328. 9 Kayama, Y., Negi, T., Sugitani, M. and Iwama, K., Effects of locus coeruleus stimulation on neuronal activities of dorsal lateral geniculate nucleus and perigeniculate reticular nucleus of rat, Neuroscience, 7 (1982) 655-666. 10 Kvale, I., Fosse, V.M. and Fonnum, F., Development of neurotransmitter parameters in lateral geniculate body, superior colliculus and visual cortex of the albino rat, Dev. Brain Res., 7 (1983) 137-145. 11 Le Gros Clark, W.E., The problem of regeneration in the central nervous system. 1. The influence of spinal ganglia and nerve fragments grafted in the brain, J. Anat., 77 (1942) 20-48. 12 Lund, R.D. and Lund, J.S., Synaptic adjustment after de-
192 afferentation of the superior colliculus of the rat, Science, 171 (1971) 804-807. 13 Lund-Karlsen, R. and Fonnum, F., Evidence for glutamate as a neurotransmitter in the corticofugal fibres to the dorsal lateral geniculate body and the superior coUiculus in rats, Brain Research, 151 (1978) 457-467. 14 Madison, R. and Davis, J.N., Sprouting of noradrenergic fibers in hippocampus after medial septal lesions: contributions of the central and peripheral system, Exp. Neurol., 80 (1983) 167-177. 15 Matute, C., Waldvogel, H.J., Streit, P. and Cuenod, M., Selective retrograde labeling following D-[3H]aspartate and [3H]GABA injections in the albino rat superior colliculus, Neurosci. Lett., Suppl. 18 (1984) S 190. 16 Mize, R.R., Spencer, R.F. and Sterling, P., Two types of GABA-accumulating neurons in the superficial grey layer of the cat superior colliculus, J. Comp. Neurol., 206 (1982) 180-192. 17 Moore, R.Y., Bjrrklund, A. and Stenevi, U., Plastic changes in the adrenergic innervation of the rat septal area in response to denervation, Brain Research, 33 (1971) 13-35. 18 Moore, R.Y. and Bloom, F.E., Central catecholamine neuron system: anatomy and physiology of the norepinephrine and epinephrine systems, Annu. Rev. Neurosci., 2 (1979)
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19 Nadler, J.V., Cotman, C.W. and Lynch, G.S., Biochemical plasticity of short-axon interneurons: increased glutamate decarboxylase activity in the denervated area of rat dentate gyrus following entorhinal lesion, Exp. Neurol., 45 (1974) 403-412. 20 Opstad, P.K., Aakvaag, A. and Rognum, T.O., Altered hormonal response to short-term bicycle exercise in young men after prolonged physical strain, caloric deficit, and sleep deprivation, Eur. J. Appl. Physiol., 45 (1980) 51-62. 21 Ottersen, P.P. and Storm-Mathisen, J., Neurons containing or accumulating transmitter amino acids. In A. Bjrrklund, T. Hrkfelt and M.J. Kuhar, (Eds.), Handbook
29
30
31
of Chemical Neuroanatomy, Vol. 3, Classical transmitters and transmitter receptors in the CNS Part II, Elsevier, Amsterdam, 1984, pp. 141-246. Rogowski, M.A. and Aghajanian, G.K., Activation of lateral geniculate neurons by norepinephrine: mediation by an a-adrenergic receptor, Brain Research. 182 (1980) 345-359. Rose, G., Lynch, G.S. and Cotman, C.W., Hypertrophy and redistribution of astrocytes in the deafferented dentate gyrus, Brain Res. Bull., 1 (1976) 87-92. Roubein, I.F. and Embree, L.J., Post mortem stability of catecholamines in discrete regions of rat brain, Res. Comm. Chem. Pathol. Pharmacol. , 23 (1979) 143-153. Sakaguchi, R., Shirokawa, T. and Nakamura, S., Changes in projection from locus coeruleus to lateral geniculate nucleus following ablation of visual cortex in adult rats, Brain Research, 321 (1984) 319-322. Schneider, G.E., Early lesions of superior colliculus: factors affecting the formation of abnormal retinal projections, Brain Behav. Evol., 8 (1973) 73-109. Siesjr, B.K. and Ingvar, M., Blood flow. In A. Lajtha (Ed.), Handbook of Neurochemistry, Vol. 3, Metabolism in the Nervous System, Plenum, New York, 1983, pp. 653-688. Somogyi, J., H~mori, J. and Silakov, V.L., Free postsynaptic sites in the lateral nucleus of adult cats following chronic decortication, Cell Tiss. Res., 225 (1982) 437-442. Somogyi, J., H~imori, J. and Silakov, V.L., Synaptic reorganization in the lateral geniculate nucleus of the adult cat following chronic decortication, Exp. Brain Res., 54 (1984) 485-498. Stenevi, U. and Bjrrklund, A., Growth of vascular sympathetic axons into the hippocampus after lesions of the septohippocampal pathway: a pitfall in brain lesion studies, Neurosci. Lett., 7 (1978) 219-224. Stenevi, U., Bjrrklund, A. and Moore, R.Y., Growth of intact central adrenergic axons in the denervated lateral geniculate body, Exp. Neurol., 35 (1972) 290-299.
189
BRE21528
Biochemical plasticity in the superior colliculus of adult rats after chronic visual cortex ablation VIGGO M. FOSSE and PER K. OPSTAD
Norwegian Defence Research Establishment, Division for Environmental Toxicology, N-2007 Kjeller (Norway) (Accepted January 14th, 1986)
Key words: visual cortex - - superior colliculus - - r~-Aspuptake - - glutamate decarboxylase - - noradrenaline - - plasticity - - rat
We have measured the changes of several neurochemical parameters in the adult rat superior colliculus (SC) 1.5-4 months after unilateral visual cortex ablation. High-affinity uptake of D-[3H]Aspwas increased by 22.5% and glutamate decarboxylase by 10% in the ipsilateral SC. This may be largely attributed to reactive synaptogenesis of intrinsic glutamatergic and GABAergic neurons, respectively. The noradrenaline content was increased by about 60 and 25% in the ipsi- and contralateral SCs, respectively. The latter probably reflects sprouting of noradrenergic fibres from the locus coeruleus.
Ablation of the visual cortex (VC) in adult rats brings forth a substantial increase in the number of noradrenaline (NA)-containing terminals in the lateral geniculate body (LGB) 25,31 as judged by histofluorescence. It is thought that this reflects plastic changes (sprouting) of ascending fibres from the locus coeruleus 25. Also, plastic changes with concomitant increased noradrenergic innervation has been demonstrated in the septal area after fimbria lesion 17 and in hippocampus after medial septal lesion in adult rats 14. Lesions have also been shown to provoke plastic changes in the superior colliculus (SC) 12'26 which were attributed to a 'pruning effect' of remaining axons. Previously, we have shown that VC ablation reduces high-affinity uptake of D-aspartate in SC by 30-35% in adult rats when measured one week postsurgery 7'z°'13. Thus, evidence has been obtained to suggest glutamate (and/or aspartate) as transmitter(s) of visual corticofugal afferents in SC. In addition, the SC harbors a considerable number of local (intrinsic) Glu-neurons 7 and G A B A neurons 16. Most likely, only a small fraction of the retinotectal fibres seem to employ Glu as their transmitter 7. In deafferented brain regions degeneration of
nerve terminals elicits hypertrophy, redistribution and some proliferation of astrocytes 3'23, which accumulate acidic amino acid neurotransmitters avidly ~,6. Moreover, in the hippocampus deafferentation provokes reactive synaptogenesis 3. In this study we have therefore investigated by biochemical methods to what extents catecholaminergic, glutamatergic, G A B A e r g i c and cholinergic parameters in the SC of adult rats were affected several months after VC ablation. This was done in order to monitor possible plastic changes in the SC after chronic deafferentation as judged by the biochemical criteria. Adult male Wistar rats, 160-180 g (M~llergaard Avlslaboratorium, Denmark) were employed. Surgical procedures and tissue preparation were similar to those described by Fosse and Fonnum 7, as were the methods to measure high-affinity uptake of D-[3H] aspartate (D-[3H]Asp), glutamate decarboxylase ( G A D ) , choline acetyltransferase (CHAT) and protein. Animals to be used for catecholamine (CA) analysis were killed by decapitation. The heads were chilled in liquid N2 and the visual part 8 of SC was dissected from 600-/~m-thick slices. The pia with adher-
Correspondence: V.M. Fosse. Present address: Norwegian Underwater Technology Center, P.O. Box 6, N-5034 Ytre Laksevfig, Bergen, Norway. 0006-8993/86/$03.50 © 1986 Elsevier Science Publishers B.V. (Biomedical Division)
190 TABLE I High-affinity uptake of o-[3H]Asp GAD and ChAT activities in the adult rat superior colliculus 3..5 months after unilateral visual cortex ablation.
Results are presented as nmol.g protein-l.h-~ for D-[3H]Asp and as/~mol.g protein-Lh -1 for GAD and CHAT. Values are means _+ S.E.M. Differences between non-operated (control) and operated (deafferented) sides: * P < 0.001 (Student's t-test). Activities in SC on the non-operated side did not differ significantly from those in the SC of non-operated animals of the same age. Control
D-[3H]Asp 525 _+ 19 GAD 245 + 3 ChAT 22.5_+ 0.8
Deafferented
% Change
n
644 __+16" 270 + 2* 23.1 + 0.4
+22.5 +10.1 + 3.2
11 6 6
ing vasculature and b l o o d were r e m o v e d from the tissue by immersion in ice-cold 0.32 M sucrose. Subsequently each slice (ca. 10 mg) was transferred to 1 m l ice-cold 0.2 M perchloric acid ( P C A ) , homogenized by hand in a glass-glass h o m o g e n i z e r and extracted for 15 rain on ice. C A concentrations in the extracts were d e t e r m i n e d by a radioenzymatic m e t h o d 4,2°. P o s t m o r t e m changes of C A s were not a p r o b l e m in this study in light of the relatively short time interval (i.e. less than 5 min) from decapitation to P C A - e x traction 24. In Table I is shown that 3.5 months after VC ablation D-[aH]Asp and G A D in h o m o g e n a t e s of the deafferented SC was increased by 22.5 and 10.9%, respectively, relative to the contralateral SC. The
TABLE II Effects of chronic VC ablation on content of NA and DA in the adult rat superior coUiculus
Results are presented as pmol/mg protein (mean + S.E.M.). Numbers in parentheses underneath the values are the % change relative to unoperated controls of the same age. Differences between operated and non-operated animals were: * P < 0.05, ** P < 0.001 and *** P < 0.0001 (Student's t-test).
NA
Time after lesion
Non-operated side
Operated side
n
- (control 1.5 months
22.3 _+0.6 26.9 _ 1.8" (+21%) 29.0 + 2.4* (+30%) 9.3 +_ 1.1 10.9 + 0.2 10.6 + 0.6
35.7 ___2.7** (+60%) 36.7 + 1.4"** (+65%) 11.6 +_0.3 10.8 + 0.7
6 6
4 months DA
- (control) 1.5 months 4 months
5 6 6 5
change in C h A T activity was only marginal and not statistically significant. In contrast, 6 months after unilateral enucleation D-[3H]Asp in the contralateral SC was reduced by 26% relative to the control SC. G A D was reduced by 10%, whereas C h A T was not affected (unpublished observation). The contents of N A and d o p a m i n e ( D A ) in the SC of n o n - o p e r a t e d adult rats were 22.3 and 9.3 p m o l ' g protein -1, respectively (Table II). The adrenaline content was 1.15 pmol/mg protein. Changes in the content of catecholamines were measured in the SC of adult rats at two time-points after unilateral VC ablation. The control values of n o n - o p e r a t e d adult rats were obtained from animals of the same age as those with chronic visual cortex ablations. In the ipsilateral SC N A was increased by 60% c o m p a r e d to the controls (Table II). In the contralateral SC N A was increased as well, but only by 2 0 - 3 0 % . The changes found after 1.5 months were retained or slightly increased 4 months postsurgery. In contrast, the D A content was not affected significantly by VC ablation (Table 1I), nor was the adrenaline content affected. In previous studies we have found that short-term (i.e. 1 week) VC ablation reduces D-[3H]Asp uptake in the ipsilaterai SC by 3 0 - 4 0 % 1(1'13, which was attributed to degeneration of glutamatergic corticofugal terminals 7. H e r e we find, however, that after long survival times homogenates of the deafferented SC accumulate D-[3H]Asp more avidly than the controls, i.e. non-deafferented SC. The reason for this is not immediately a p p a r e n t and may be the result of several factors. It is known from other visual areas that synaptic reorganization takes place after long-term deafferentation 26'2s'29. Most likely, dendritic sprouting of intrinsic neurons contribute in this process 5'28'29. The SC harbors intrinsic Glu and G A B A neurons 7'16'21 and possibly glutamatergic corticofugal afferents of extravisual origin 15. Sprouting of Gtu and G A B A terminals may contribute to the increased D-[3H]Asp uptake and G A D activities, respectively, after chronic decortication. Increased capacity for G A B A synthesis has been observed in deafferented hippocampus 19 which most likely reflects reactive synaptogenesis of intrinsic G A B A neurons 3. Thus, reactive synaptogenesis of intrinsic Glu and G A B A neurons may also take place in the SC after chronic deafferentation.
191 Shrinkage (i.e. atrophy) of the SC could also contribute to the o b s e r v e d increases of D-Jail]Asp uptake, G A D and N A . H o w e v e r , this is an unlikely explanation. Otherwise C h A T and D A would also be expected to increase. Conceivably, the increased D-[3H]Asp uptake could also be due to the presence of reactive astrocytes which proliferate and redistribute in the terminal area after deafferentation 23'31 and which have a high capacity for amino acid u p t a k e 1. H o w e v e r , the astrocytic reaction is an early response which occurs during the first two weeks after deafferentation 3"23. Most likely, they are not responsible for the increase in D-[aH]Asp uptake. R a t h e r , they may supply trophic factors which p r o m o t e terminal sprouting 3. The possibility that ingrowth of vascular sympathetic axons 2'11'3° and increased vascularization 25 contribute to increased D-[3H]Asp u p t a k e and N A content of the deafferented SC can not be entirely excluded. Since the D A and N A innervation of cerebral vessels is still elusive 27 it is at present difficult to discuss this point. The n o r a d r e n e r g i c p r o j e c t i o n from L C arises very early in development, and retains a m a r k e d propensity to form axon collaterals in response to cellular injury also in a d u l t h o o d TM. The L C afferents have a diffuse topographic distribution whereas the D A fibres a p p e a r m o r e topographically restricted and less responsive to injury TM, which c o r r o b o r a t e s our finding that only the N A system was affected in the rat SC after chronic VC ablation (Table II). Also, the per-
1 Balcar, V.J., Borg, J. and Mandel, P., High affinity uptake of L-glutamate and L-aspartate by glial cells, J. Neurochem., 28 (1977) 87-93. 2 Boast, C.A., Reid, S.A., Johnson, P. and Zornetzer, S.F., A caution to brain scientists: unsuspected hemorrhagic vascular damage resulting from more electrode implantation, Brain Research, 103 (1976) 527-534. 3 Cotman, C.W. and Nadler, J.V., Reactive synaptogenesis in the hippocampus. In C.W. Cotman (Ed.), Neuronal Plasticity, Raven, New York, (1978) pp. 227-271. 4 Da Prada, M. and Ziircher, G., Simultaneous radioenzymatic determination of plasma and tissue adrenalin, noradrenaline and dopamine within the femtomole range, Life Sci., t9 (1976) 1161-1174. 5 Eysel, U. Th., Functional reconnection without new axonal growth in a partially denervated visual relay nucleus, Nature (London), 299 (1982) 442-444. 6 Fonnum, F., Glutamate: a neurotransmitter in mammalian brain, J. Neurochem., 42 (1984) 1-11. 7 Fosse, V.M. and Fonnum, F., Effects of kainic acid, and
sistence of the increased N A content for several months after surgery c o r r o b o r a t e d previous observations in L G B 25. By the histofluorescence technique no increase in N A terminals was seen in the SC after VC ablation 31 although the visual part of SC receives a relatively dense noradrenergic innervation from the locus coeruleus TM. The increase in N A may, however, have been m a s k e d by the relatively intense fluorescence of the superficial SC 31 and the bilateral increase in N A content (Table II). M o r e o v e r , Stenevi et al. 31 did only examine the decorticated animals after short survival times, i.e. 2 - 4 weeks. As shown in Table II there was a small, but still significant, increase of N A in the contralateral non-deafferented SC, also. Similarly, sprouting of LC fibres have been observed in the contralateral L G B in response to the more extensive unilateral visual cortex lesions 25. As yet, we can not conclude that there was a direct causal relationship b e t w e e n the observed changes in the noradrenergic system of the adult rat SC and the increased D-[3H]Asp uptake and G A D activity after deafferentation. O u r d a t a do, however, provide biochemical evidence for long-term plastic changes in the rat SC after chronic visual cortex ablation which presumably reflects sprouting of intrinsic neurons and u n d a m a g e d afferents. The increased density of noradrenaline terminals p r o b a b l y serves to enhance activity of remaining intrinsic neurons, as has been d e m o n s t r a t e d in the L G B 9'22'25.
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