Cortical Ablation Research Articles

Release of d-[ 3H]aspartic acid from the rat substantia nigra: effect of veratridine-evoked depolarization and cortical ablation

The spontaneous and veratridine-evoked release of radioactive d-aspartic acid, previously taken up by rat substantia nigra slices, was studied by using a superfusion system. Veratridine (25 μM, 1 min) markedly produced a 14-fold increase in d-[ 3H]aspartic acid release from nigral slices. Omission of Ca 2+ and increasing Mg 2+ concentration to 12 mM in the superfusion medium did substantially block d-[ 3H]aspartate release induced by veratridine depolarization. Nevertheless, veratridine was able to evoke [ 3H]amino acid release which seemed to be, at least, 30% Ca 2+-independent. Additional experiments showed that tetrodotoxin (0.01–0.1 μM), a blocker of voltage-dependent Na + channels, totally abolished veratridine-evoked release of d-[ 3H]aspartate from nigral slices. Lesion studies were performed in order to learn about the nature of the neuronal compartment in the substantia nigra upon which veratridine-depolarization acted to induce d-[ 3H]aspartate release. Unilateral ablation of the fronto-parietal cortex was accompanied by a significant decrease in the accumulation of nigral d-[ 3H]aspartate and by a large loss from ipsilateral nigral slices in d-[ 3H]aspartate release evoked by veratridine. In contrast, both the accumulation and veratridine-evoked release of [ 3H]dopamine, remained unchanged in the ipsilateral substantia nigra slices to the lesion. The findings reported suggest that d-[ 3H]aspartic acid may be taken up and then released, in a Ca 2+-dependent manner, by nerve terminals located in the substantia nigra. In addition, the results shown provide support to the view that l-glutamate and/or l-aspartate may act as neurotransmitters at the cortico-nigral neuronal pathway.

Altered local cerebral glucose utilization by unilateral frontal cortical ablations in rats

Alterations in local cerebral glucose utilization (LCGU) following ablations of the unilateral frontal cortex in rats were studied to elucidate the effect of the lesion on the functional activity in the related cerebral structures. Frontal cortical ablations (areas 2, 4, 6 and 10) were made by aspiration on the left side, and LCGU was evaluated at 7 days after the operation, using the [14C]deoxyglucose method. Significant decreases in LCGU in rats with unilateral frontal cortical ablations, were observed in the ipsilateral thalamic nuclei (ventroanterior-ventrolateral (VAL), ventrobasal (VB), reticular), red nucleus and pontine nucleus. The ipsilateral globus pallidus showed a significant LCGU increase. The contralateral cerebellar cortex showed a tendency toward a decrease in LCGU. The striatum, which receives direct projections from the frontal cortex, showed no LCGU change. These results indicated that ablations of unilateral frontal cortex in rats produced LCGU changes in the cerebral structures which have direct or indirect neuronal connections with the ablated area. These LCGU changes were, for the most part, brought about by alteration in the neuronal activity. Particularly, the LCGU increase in the globus pallidus which receives transsynaptic neuronal input from the frontal cortex, without changes in the striatum, which receives direct projection, was attributed to the functional alteration of the globus pallidus produced by the cortical ablation. Destructive lesion of a cerebral structure, therefore, does not necessarily cause functional depressions in the pertinent structures, but it may enhance the function of some structures, depending on the functional characteristics of each neuronal connection and functional organization of those structures.

Altered local cerebral glucose utilization by unilateral frontal cortical ablations in rats

Altered local cerebral glucose utilization by unilateral frontal cortical ablations in rats

Effect of cortico-striate pathway lesion on the activities of enzymes involved in synthesis and metabolism of amino acid neurotransmitters in the striatum.

The activities of several enzymes involved in the metabolism of aspartate and glutamate were measured in striatal (nucleus caudatus and putamen) homogenates 2-3, 6-7, and 35-40 days following frontoparietal and frontal cortical ablation. The activity of glutamine synthetase (GS) was substantially increased (46-48%) on the operated side 6-7 days following the lesion whereas smaller changes were observed at 2-3 and 35-40 days after lesion. In contrast, decreased levels of glutaminase and malate dehydrogenase (MDH) were observed by 6-7 days while no significant change was found at either 2-3 or 35-40 after the lesion. The activities of glutamate dehydrogenase (GDH) and glutamate decarboxylase (GAD) were elevated after 35-40 days whereas no changes in the levels of either GDH or aspartate aminotransferase (ASAT) were found at 2-3 or 6-7 days after the fronto-parietal decortication. When only the frontal cortex was removed quantitatively similar changes were observed in striatal GS and glutaminase activity. The content of glutamate and glutamine in the denervated striatum followed qualitatively the changes in glutaminase and GS. The results indicate that the degeneration of cortico-striatal terminals causes a profound glial reaction in the striatum, and both glutaminase and MDH are present in relatively high concentrations in the corticostriatal terminals.

In vivo binding of N-n-propylnorapomorphine in the rat striatum: quantification after lesions produced by kainate, 6-hydroxydopamine and decortication.

The neuronal localization of in vivo N-n-propylnorapomorphine (NPA) binding in the rat striatum was studied using 3 types of lesions. Striatal dopamine (DA) receptor densities (Bmax) were estimated from the relationships between total striatal and cerebellar NPA accumulation. A Bmax of 26.9 +/- 1.6 fmol X mg-1 wet weight tissue was found in the striata of non-lesioned (unoperated) rats. Similar values were obtained for striata with 6-hydroxydopamine-lesioned dopaminergic fibres. Kainate (KA)-lesioned striata contained 4.6 +/- 0.5 fmol X mg-1 saturable NPA binding sites. After unilateral decortication the receptor densities were in both striata resulting in ipsi- and contralateral Bmax values of 23 and 36 fmol X mg-1 respectively. With a tracer dose of [3H]NPA less radioactivity accumulated in the KA-lesioned striatum, while after unilateral destruction of the dopaminergic pathway more radioactivity was found in the ipsilateral striatum and no bilateral differences in striatal radioactivity concentration were found after unilateral cortical ablation. These observations show that all in vivo saturable striatal NPA binding sites are situated on striatal neurons and cortico-striatal afferents and that the effects of lesions on striatal DA receptor densities cannot be predicted from bilateral differences in the accumulation of tracer doses of [3H]NPA.

Localization of [ 3H]N-propylnorapomorphine binding in mouse striatum

The anatomic localization of specific striatal [ 3H]N-propylnorapomorphine ([ 3H]PNA) binding was determined in male C57BL/6J mice. Striatal [ 3H]PNA binding was of high affinity and sensitive to guanine nucleotides. Frontal cortical ablation did not alter striatal [ 3H]PNA binding, but reduced [ 3H]spiperone binding by 36%. Kainic acid reduced and 6-hydroxydopamine elevated [ 3H]PNA binding. A combined frontal cortical ablation and striatal kainic acid lesion was similar to that of kainate alone. These data are consistent with a localization of [ 3H]PNA binding sites on neurons intrinsic to the mouse striatum.

An electron microscope study of the cortico-pretecto-olivary projection in the cat by a combined degeneration and horseradish peroxidase tracing technique

The anterior pretectal nucleus (PTA) of the cat was observed electron microscopically after motor cortical ablation and horseradish peroxidase (HRP) injection into the inferior olive of the same animal. Direct synaptic connections were found between degenerated cortico-pretectal axon terminals and dendrites of pretecto-olivary projection neurons retrogradely labeled with HRP in the ventrolateral part of the PTA. Therefore, this combined method revealed that the PTA is a relay station of the cortico-olivary projection.

Effect of regional cortical ablations on high-affinity d-aspartate uptake in striatum, olfactory tubercle, and pyriform cortex of the rat

The ablation of medial frontal cortex, but not of other separate cortical regions, was accompanied by a significant decrease in high affinity uptake of D-Asp in neostriatum, olfactory tubercle and pyriform cortex. The results indicate that the medial frontal cortex may be an important region for glutamergic/aspartergic cell bodies.

Direct and indirect visual inputs to superficial layers of cat superior colliculus: a current source-density analysis of electrically evoked potentials

1. The spatiotemporal pattern of visual inputs to the stratum griseum superficiale (SGS) and stratum opticum (SO) of the cat superior colliculus (SC) has been determined by an analysis of the current sinks occurring during postsynaptic activity following stimulation of each optic nerve (ON) and the optic chiasm (OX). Electrolytic lesions were used to determine the locations of the five major current sinks. 2. Direct SC afferents from the contralateral ON induced three current sinks whose maxima were located a) in the upper part of the SGS, b) in the middle part of the SGS, and c) in the lower part of the SGS and upper part of the SO. These three sinks were generated by three afferent fiber groups conducting in the optic nerve with modal and maximum velocities, respectively, of a) 4 and 5 m/s (slow W-group), b) 7 and 10 m/s (fast W-group), and c) 32 and 43 m/s (Y-group). 3. Indirect SC inputs from the contralateral ON via the ipsilateral visual cortex were identified by comparing the pattern of current sinks generated by OX stimulation before and after cortical ablation. The most prominent and fastest indirect sink (Y-group) was found in ;the lower half of the SGS and uppermost part of the SO. Low-amplitude, long-latency indirect current sinks were also found in the upper and lower thirds of the SGS. 4. The principal conclusions of this report are first, that the SGS is divisible into three physiologic regions according to the spatiotemporal pattern of excitatory synaptic activity generated by the afferent inputs and second, that there is a spatiotemporal matching of the direct collicular afferents from the contralateral retina and the indirect retinal afferents relaying through the ipsilateral visual cortex.

Altered activity in the hippocampus is more detrimental to classical conditioning than removing the structure.

Hippocampal ablation has no effect on the acquisition of the rabbit's classically conditioned nictitating membrane response. Systemic administration of scopolamine, which alters hippocampal neuronal activity, severely retards acquisition of the conditioned response in normal animals and those with cortical ablations. In animals with hippocampal ablations, however, scopolamine has no effect on conditioning. These findings suggest that altered neuronal activity in the hippocampus is more detrimental to conditioning than removing the structure.

Glutamate uptake, glutamate decarboxylase and choline acetyltransferase in subcortical areas after sensorimotor cortical ablations in the cat

High affinity glutamate uptake (HAGU), glutamate decarboxylase (GAD) and choline acetyltransferase (CAT) activities were measured from subcortical nuclei in the cat brain after ipsilateral ablation of the sensorimotor cortex. Results showed a drop in HAGU in all the structures assayed except the subthalamic nucleus. These changes in HAGU are generally accompanied by a decrease in GAD while CAT is unaffected. However, in the red nucleus the drop in HAGU is concomitant to an increase in GAD and CAT. In the subthalamic nucleus HAGU and CAT are increased while GAD is decreased. These results are consistent with the concept that most corticofugal fibres to subcortical structures use glutamate as their neurotransmitter. Results concerning GAD suggest that GABAergic subcortical neurons are under a cortical influence. This influence seems to be weak on cholinergic neurons.

Intracellular study of presumed interneurons in the ventrobasal complex of cats with chronic cortical ablations.

In a ventrobasal neuronal population surviving chronic ablation of somatosensory and motor cortices, the input-output properties of cells activated by ML fibers and showing functional characteristics of interneurons (large peripheral receptive fields, convergence of different types of receptor afferents, repetitive discharge) were studied. Since intracellular recordings showed the presence of excitatory and inhibitory postsynaptic potentials, it is argued that inhibitory interneurons also receive inhibitory inputs, suggesting that data processing in VB is more complex than hitherto postulated.

Cortical modulation of cholinergic neurons in the striatum

Previous reports suggest the existence of a cortico-striatal pathway which might use glutamate as the transmitter. In the present study, the possible influence of this pathway on striatal cholinergic neurons was investigated. Two weeks following surgical destruction of the cerebral cortex, the high affinity uptake of glutamate and choline into striatal synaptosomes was significantly reduced whereas GABA uptake was unaffected. In acute experiments (1 hour following decortication), only choline uptake was significantly reduced while the uptake of glutamate and GABA were not altered. Acute injection (2 minutes) of kainic acid into the striatum, 1 hour after decortication, reversed the effect of the decortication on choline uptake, perhaps by simulating an excitatory input to the striatum which was presumably removed by the cortical ablation. These observations are consistent with the existence of a cortical input (perhaps glutamatergic) to the striatum and suggest that striatal cholinergic neurons can be influenced by this cortico-striatal pathway.

A Model for Oral Dyskinesia in Rats

Rats subjected to bifrontal cortical ablations developed vacuous chewing movements and jaw tremors that began 22 weeks after surgery, reached a peak rate of 4 to 8 per minute, and remained stable for an 8-week observation period. Chronic haloperidol administration to rats with bifrontal cortical ablations produced 15 to 20 movements per minute that persisted for 7 weeks after drug withdrawal. Drugs given to decrease dopaminergic, cholinergic, and gamma-aminobutyric acid (GABA)-ergic neurotransmission suppressed the movements, whereas cholinergic agonists increased them. This model of oral dyskinesia in rats may be useful in developing drugs for the treatment of facial dyskinesias in humans.

Operant behavioral analysis of memory loss in monkeys with prefrontal lesions

The effects of dorsolateral prefrontal cortical ablation were examined in rhesus monkeys preoperatively trained to perform two versions of an indirect spatial delayed-response task. In one task (DR I), the stimulus keys that signaled the position of the reward were accessible throughout a trial. Thus, the monkeys could orient to the positive side (‘rehearse’) by continuing to press the correct key during the delay. The other task, DR II, was designed to disrupt bodily orientation and to prevent ‘rehearsal’. In this task the monkeys were required to press an extraneous upper key during the delay. After bilateral ablation of the prefrontal cortex, 3 out of the 4 monkeys easily regained preoperative levels of performance on the DR I task, but all subjects were markedly impaired in the DR II task on which they exhibited strong position preferences. These deficits were ameliorated by eliminating the position biases through training with short delay intervals followed by gradual increments in delay length. Analysis of the location of key presses during each phase of delayed-response trials showed that the monkeys press the correct key in the cue period even when they subsequently made incorrect responses. A consistent finding was that operated monkeys shifted their response to the incorrect key early in the delay period regardless of its duration, whenever the correct side was the nonpreferred side. These results support the idea that delayed-response deficits in monkeys with prefrontal lesions may be due in part to a defect in registering or encoding the correct spatial position in memory rather than to a loss in storage or retrieval processes.

Effects of caudate nuclear or frontal cortical ablation in neonatal kittens or adult cats on the spontaneous firing of forebrain neurons

In this paper we have determined the long-lasting consequences of caudate and frontal cortical lesions on spontaneous neuronal firing. Lesions were made both in neonatal and adult cats. All recordings were made in adults. Qualitatively, the effects of the caudate ablations were similar whether they had been carried out in kittens or in adult cats. Caudate lesions produced long-lasting (≥ 1 year) decreases in the spontaneous firing of cortical neurons. These changes were more pronounced when made in neonates than in adults. The distributions of mean interspike intervals were also altered by these caudate lesions in the pallidum and in the ventral lateral nucleus of the thalamus. Again these effects were more marked if the animals were lesioned as neonates than as adults. Frontal cortical lesions inflicted upon adult cats produced more widespread changes in spontaneous firing rates than similar lesions made in neonates. In both groups frontal lesions slowed spontaneous firing and changed the distributions of mean interspike intervals of caudate neurons. These effects were long-lasting (≥ 1 year in neonatally-ablated animals). Cortical lesions made in adult cats markedly altered thalamic and pallidal spontaneous activity. Similar lesions made in neonates produced relatively small changes in thalamic and pallidal activity.

N-methyl-C-aspartate-type receptors mediate striatal 3H-acetylcholine release evoked by excitatory amino acids.

Several lines of evidence suggest that striatal cholinergic inter-neurones receive an excitatory input from the cerebral cortex which utilizes an excitatory amino acid, L-glutamate or L-aspartate, as its neurotransmitter. Cortical ablation reduces striatal high-affinity glutamate uptake1,2 and concomitantly decreases acetylcholine turnover3. The destruction of cholinergic, as well as other, neurones of the striatum by the rigid glutamate analogue kainic acid seems to require a functional excitatory amino acid innervation4,5. Furthermore, electron microscopic studies6 suggest the existence of a cortical input to the aspiny dendrites of neurones morphologically similar to the presumed striatal cholinergic interneurones7,8. The recent discovery of preferential antagonists of amino acid-induced excitation in the vertebrate central nervous system has led to the classification of excitatory amino acid receptors into three subtypes: the N-methyl-D-aspartate (NMDA), the quisqnalate-and the kainate-preferring receptors9. We have now attempted to characterize the receptor(s) mediating the excitatory amino acid influence on striatal cholinergic neurones by investigating the effects of specific excitatory amino acid receptor agonists and antagonists on the release of 3H-acetylcholine from slices of the rat corpus striatum. We find that excitatory amino acid analogues evoke a tetrodotoxin-sensitive release of 3H-acetylcholine from rat striatal slices superfused in Mg2+-free medium, NMDA and ibotenate being the most potent and kainate and quisqualate the least potent. This effect is antagonized by Mg2+ and by (−)2-amino-7-phosphonoheptanoate (−APHept) and (±)2-amino-5-phosphonopentanoate (±APPent) but not by glutamic acid diethyl ester (GDEE). These data suggest the involvement of a NMDA-type receptor in the excitatory amino acid influence on striatal acetylcholine release.

The distribution of lateral funicular and cortical fibers to the dorsal column, Z and X nuclei in the prosimian Galago

The distribution of lateral funicular and cerebral corticofugal fibers to the dorsal column, Z and X nuclei were studied in the prosimian primate Galago senegalensis. Lesions of the lateral funiculus resulted in a differential distribution pattern of preterminal degeneration within the nuclei studied. In the nucleus gracilis, spinal lesions produced moderate amounts of debris in ventral cell nest and rostral areas. Diffuse degeneration was present in both the dorsal cell nest area of the nucleus gracilis and the rostral nucleus cuneatus. Extremely dense debris was present within both ipsilateral Z and X nuclei. Cortical ablations of predominantly hind-limb motor-sensory areas resulted in degeneration throughout most of the longitudinal and transverse extent of the contralateral dorsal column nuclei. Degeneration appeared to be more concentrated in ventral nuclear areas. The distribution of cortical fibers to the rostral gracile and Z nuclei was essentially the inverse of that observed for lateral funicular fibers. The contralateral nucleus Z received only a sparse corticobulbar input while the rostral gracile contained more moderate amounts of preterminal degeneration. The results are in agreement with previous reports on the morphology and fiber connections of the dorsal column, Z and X nuclei in Galago and other animals. They support the concept that the Z and X nuclei are functional components of the dorsal column nuclear system.

Effect of motor and premotor cortex ablation on concentrations of amino acids, monoamines, and acetylcholine and on the ultrastructure in rat striatum. A confirmation of glutamate as the specific cortico-striatal transmitter.

At 1, 2, and 4 weeks after unilateral premotor and motor cortex ablation in rats, a significant and lasting decrease in glutamate levels in the ipsilateral versus contralateral striatum was observed. A significant corresponding fall in aspartate was seen only after 1 week. In contrast, there was a large increase in the striatal concentrations of lysine, threonine, alanine, and glutamine 1 week after the cortical ablation. This correlates with the extensive glial proliferation in the deafferented ipsilateral striatum. Four weeks after cortical ablation the GABA concentration was significantly increased. There was no decrease in other putative transmitters (dopamine, serotonin, acetylcholine, glycine and taurine), nor was a glutamate decrease observed in the hippocampus or in the hypothalamus, which do not receive direct premotor and motor cortical inputs. Both biochemical and morphological evidence for a minor contralateral cortico-striatal projection was obtained. Correlating with the fall in glutamate, ultrastructural observations indicated the degeneration of two types of striatal synapses, i.e., those of the axo-spinous type III and of the axo-dendritic type VII. Frontal cortex ablation clearly affects, in opposite directions, the metabolism of various striatal amino acids but not that of acetylcholine and the monoamine transmitters. The results strongly support the view that glutamate is the transmitter of the cortico-striatal fibers.

The effect of entorhinal cortical ablation on the distribution of muscarinic cholinergic receptors in the rat hippocampus

Removal of the entorhinal cortical projection to the hippocampus in adult rats decreased the density of muscarinic cholinergic receptors in the denervated dentate gyrus outer molecular layer at two days postlesion. Thirty days following the lesion (in adults and neonates) there is a small receptor density increase in the outer molecular layer (may be due to tissue shrinkage), and a larger increase in the lacunosum-moleculare. The receptor density decrease seen two days postlesion suggests the presence of presynaptic muscarinic receptors on the lost entorhinal cortical fibers. The distribution and extent of the receptor changes seen at 30 days postlesion are inconsistent with the cholinergic fiber reorganization which follows an entorhinal cortical lesion, but are consistent with a proposed model of non-cholinergic afferent mediated control of muscarinic receptor density in the rat hippocampus.