Neocortical Ablations Research Articles

Learning impairments in monkeys with combined but not separate excitotoxic lesions of the anterior and mediodorsal thalamic nuclei

Clinical studies in humans and experiments in macaques suggest that damage to the anterior and the mediodorsal thalamus can induce a moderate amnesia, but a more dense impairment may result from substantial damage within the temporal lobes or their subcortical connections. Lesions of the anterior thalamus in macaques produce impairments which resemble those seen after lesions of the fornix–mamillary pathway, which carries projections from the hippocampus to the anterior thalamus, while lesions of the mediodorsal thalamus, which receives inputs from frontal and temporal cortex, produce moderate impairments on a wider range of memory tasks. In the present study, we have made bilateral excitotoxic lesions of either the anterior or the mediodorsal thalamus, or both, in marmoset monkeys. Monkeys with lesions of both thalamic nuclei were severely impaired on retention and new learning of examples of the visuospatial conditional task, a task which is specifically impaired by lesions of the fornix or hippocampus. They were not impaired on performance of a visuovisual conditional task on which monkeys with hippocampal lesions are impaired, nor were they impaired on any visual discrimination task, including the concurrent discrimination task on which monkeys with temporal neocortical ablations are impaired. Monkeys with separate lesions of either the anterior or the mediodorsal thalamus were not impaired on any of these tasks. These results suggest that the mediodorsal thalamus and the anterior thalamus are both involved in processing the output of the hippocampal–fornix–thalamic circuit. Dense amnesia may result from damage to circuits additional to the temporal lobe efferents to either the anterior or the mediodorsal nuclei.

Development of experimental allergic encephalomyelitis after neocortical brain ablations in left- and right-biased rats

Development of experimental allergic encephalomyelitis after neocortical brain ablations in left- and right-biased rats

Asymmetric increase in substance P immunoreactivity in the rat and guinea pig substantia nigra after unilateral neocortical ablation

Substance P was visualized in the rat and the guine pig basal ganglia, mesencephalon and spinal cord after surgical unilateral cortical ablation. An increased density in substance P-like immunoreactive patterns in the substantia nigra was observed ipsilaterally to the lesioned hemisphere. These results, together with previous observations in cases of Alzheimer's disease presenting with asymmetric cortical atrophy, suggest an influence of the corticostriatal pathway on substance P-like immunoreactivity in these subcortical structures. Finally, these experiments proved to be a reliable animal model for the study of the effects of neocortical lesions on the neuropeptidergic innervation of certain subcortical regions.

Contributions of hippocampus and neocortex to the expression of ethanol effects.

The distinctive effects of ethanol on behavior suggest that certain parts of the CNS may be especially sensitive to it. One of the primary candidates is the hippocampal formation. Damage to this structure mimics acute ethanol treatment across a wide variety of behavioral tasks and processes. The possibility of a hippocampal basis for ethanol psychopharmacology was examined in the present experiments. Chosen for behavioral analysis were relatively complex eight-arm radial maze tasks which have independently been shown to be sensitive to ethanol administration and hippocampal lesions. Measures included arm selection predictability, vigilance, and retardation of extinction. Bilateral hippocampal lesions or ethanol injection (1.5 g/kg, IP) produced similar effects. However, hippocampectomy did not disrupt ethanol's influence on any task. Comparatively, neocortical ablation, especially prefrontal, was quite effective in this respect. It blocked or reduced two of the drug's three behavioral effects examined here, without any strong influence of its own, and without altering blood alcohol concentration.

New evidence for distinct patterns of brain organization in rats differentiated on the basis of inherent laterality

The purpose of the present study was to search for possible relationships among diverse measures of behavioral laterality in a non-human species or to identify an index of laterality that was predictive of other non-lateralized functions. Several indices of behavioral laterality and open field activity were assessed in male and female rats before and after asymmetric neocortical ablations. Plasma adrenocorticotropin, corticosterone, and prolactin were measured following stress at sacrifice. Sex-dependent population-level lateral biases were observed preoperatively in the choice of arms in a T-maze and initial direction out of a corner of an open field. Unilateral left neocortical ablation induced a leftward bias in the T-maze in both male and female rats. The direction of rotation following the peripheral administration of amphetamine was correlated with: (a) the degree of sensitization to amphetamine; (b) preoperative open field activity in females; (c) the induction of hyperactivity following right neocortical ablation in males; (d) rotational responses to amphetamine in male rats sustaining bilateral ablations; and (e) the effect of left neocortical ablation on prolactin levels in males. We propose that these data provide new evidence for distinct patterns of brain organization in rats differentiated by a measure of inherent cerebral laterality.

Alcohol aversion generalization in rats: specific disruption of taste and odor cues with gustatory neocortex or olfactory bulb ablations.

Rats with ablations of the gustatory neocortex (Experiment 1) and rats with olfactory bulb ablations (Experiment 2) were compared with normal rats for aversion generalization to both single taste solutions (sucrose, sodium chloride, quinine hydrochloride, hydrochloric acid) and compound taste solutions (pairs of the four single tastants) following alcohol aversion training. All rats acquired equal and strong alcohol aversions. Control rats showed consistent aversion generalization to both the sucrose + quinine and the sucrose + hydrochloric acid solutions; no significant generalization occurred to the single tastants except a weak generalization to sucrose in Experiment 2. Rats with gustatory neocortical ablations failed to show aversion generalization to any of the taste solutions. Rats with olfactory bulbectomies displayed the same aversion generalization functions as control rats but exhibited significantly faster extinction of the alcohol aversion than did the trained control rats. Results from the present experiments suggest that during alcohol aversion learning, rats lacking gustatory neocortex use odor cues (no taste generalization), whereas rats lacking olfactory bulbs utilize taste cues (normal taste generalization).

Consequences of Bilateral Brain Neocortical Ablation on Imuthiol‐Induced Immunostimulation in Micea

Consequences of Bilateral Brain Neocortical Ablation on Imuthiol‐Induced Immunostimulation in Mice^a

Substantia nigra stimulation evoked antidromic responses in rat neostriatum.

Electrical stimulation of the substantia nigra of rats elicits a burst of small amplitude waves with a latency of 4-6 ms that may last for 10-15 ms throughout much of the neostriatum. Frontal cortex stimulation also elicits a burst response, which can occlude the substantia nigra response. The substantia nigra evoked burst response was still present after chronic neocortical ablation or thalamic transection or both treatments combined. The response corresponds to the first sharp negative wave of the substantia nigra evoked neostriatal field potential. Single substantia nigra evoked action potentials were recorded in neostriatum with a mean latency of 9.8 ms, ranging from 4-22 ms. These action potentials were considered to be antidromic because they were occluded during appropriate collision intervals by orthodromic action potentials elicited by frontal cortex stimulation. Subthreshold frontal cortex conditioning stimulation did not alter the threshold for activation from substantia nigra. The refractory period for the axon was at least as long as that for the soma and ranged between 0.8-2.0 ms. The antidromic responses failed to follow low frequency stimulation (less than 40 Hz for 3000 ms). This failure occurred in the axon between substantia nigra and globus pallidus. The burst response and first sharp negative wave of the field potential probably represent the antidromic activation of the ubiquitous and densely packed medium spiny neostriatal projection neurons. These responses occur at the same latency, respond in the same manner to twin pulse and repetitive stimulation and are occluded by frontal cortex stimulation in the same manner as antidromic action potentials.

Ingestive responses to homeostatic challenges in rats with ablations of the anterolateral neocortex.

Because rats with either anterolateral neocortical or lateral hypothalamic (LH) damage initially display similar feeding and drinking deficits and recovery patterns, the possibility that anterolateral neocortical ablations would also produce similar chronic ingestive impairments to glucoprivic and hydrational challenges was examined. In general, rats with anterolateral neocortical ablations exhibited normal feeding responses to food deprivation and glucoprivation induced by insulin or moderate doses of 2-deoxy-D-glucose (2-DG), but their response to a high dose (500 mg/kg) of 2-DG was impaired. These animals also drank normally in response to hypertonic saline injections and following water deprivation, but only if food was available during the test session, results indicating that they drank prandially. Results indicate that although the anterolateral neocortex and LH are anatomically related, these brain regions appear to be functionally dissimilar in terms of the regulation of ingestion.

2-Deoxyglucose uptake in the thalamus of awake rats after neocortical ablations

Local, temporary or permanent depressions and elevations in 2-deoxy[ 14C]glucose (2-DG) uptake were obseved in the brains of unanesthetized, freely moving rats that 3 days to 1 year earlier had sustained large unilateral posterior neocortical ablations. Some of the differences in metabolic activity between the normal and damaged hemispheres, in both cortical and subcortical regions, were attributed to cell death and gliosis, and surgical trauma. In addition, it appeared that certain metabolic changes provided a physiologic correlate of diaschisis, a temporary impairment in function which von Monakow hypothesized to occur in neurons denervated by a lesion. We concluded that the 2-DG technique is a useful tool for examining the widespread effects of brain damage, and that when employed in the manner exemplified by this and a previous study, the technique can disentangle the changes in neural activity which occur after brain damage from the changes in glial activity which accompany them.

Detour problem-solving behavior in rats with neocortical and hippocampal lesions: A study of response flexibility

Young rats previously subjected to discrete neocortical ablations or hippocampal electrolytic lesions received five trials on each of three “climbing” detour problems. Performance on Trial 1 (a measure of response flexibility) of each problem was significantly impaired in those groups with frontal, parietal, or hippocampal lesions; the group with occipital lesions was impaired on only one problem. Performance on Trials 2–5 (a measure of detour habit formation) of each problem was significantly impaired only in the hippocampal group; the neocortical groups showed either no impairment or a mild impairment on these trials. These results suggest that the solution of detour problems on the first trial may require a cognitive process that is qualitatively different from that required on subsequent trials.

2-Deoxyglucose uptake and histologic changes in rat thalamus after neocortical ablations

2-Deoxy[ 14C]glucose (2-DG) uptake was examined in pentobarbital-anesthetized rats that 3 days to 2 years earlier had sustained large posterior neocortical ablations. At 2 weeks postoperatively 2-DG uptake was pronounced in those thalamic nuclei with cortical projection zones included in the ablated region. At shorter postoperative intervals (3 to 4 days) there appeared to be no increases in 2-DG uptake in these thalamic nuclei and at longer postoperative intervals (>1 month) increases were only discernible in calcified sites. Both temporal and spatial postoperative variations in 2-DG uptake were found to coincide almost perfectly with glial cell proliferation and staining in the affected regions.

Laterization of spatial preference in the female rat

Female rat pups were either left undisturbed in infancy and raised in lab cages or were handled in infancy and raised in enriched environments. In adulthood, animals underwent brain surgery consisting of: 1) a right neocortical ablation, 2) a left neocortical ablation, 3) a sham operation, or 4) no surgery. After recovering, they were tested for the initial direction of movement (left or right) in the open field. Nonhandled intact females were biased to move leftward indicating an asymmetrical brain organization. The intact handled-enriched group was unbiased. The right and left lesions caused the animals to move ipsilateral to the lesion, but there was no difference in the magnitude or response in either early experience group. Thus, early experience in the female rat has a different effect then in the male, and the nature of the brain organization in the two sexes is markedly different.

Handling in infancy, brain laterality and muricide in rats

Rats were handled for the first 20 days of life or were not disturbed. Between 21 and 50 days approximately half of each group was reared in enriched environments while the remainder was group reared in laboratory cages. When adult, four males from each litter received a right neocortical ablation, a left ablation, a sham operation, or no surgery. They were tested for mouse killing between 9–12 months of age. Intact non-handled controls without enrichment experience had a 96% incidence of muricide. Handling and enrichment treatments independently and additively reduced the rate of mouse killing in animals with intact brains. There was no evidence of brain laterality for animals which received no extra stimulation in early life. In contrast, the brains of handled animals were lateralized, with the left lesion group having a higher killing response than the right. Non-lesioned handled rats had approximately the same level of muricide as those with a right hemisphere lesion, leading to the inference that in the intact brain the left hemisphere inhibits the killing response of the right.

A comparison of lateral peristriate and striate neocortical ablations in the rat

The effects of striate, lateral peristriate and sham ablations upon the postoperative reacquisition of visual discriminations were studied in two experiments. The results of Experiment 1 indicated that lesions restricted to the lateral peristriate neocortex rendered the rat incapable of resolving an oblique stripe discrimination. Seven of the 9 rats with striate ablations were unable to form the discrimination. The histological findings indicated that the deficit following lateral peristriate injury was not due to interruption of the geniculostriate system. However, the behavioral impairment in destriate rats corresponded to the degree of unintentional injury in lateral peristriate neocortex, but not medial peristriate tissue. In Experiment 2, the effects of these lesions were studied upon the postoperative reacquisition of either a non-reversal or reversal of a preoperatively acquired brightness discrimination. Animals with striate damage demonstrated considerable savings on the non-reversed brightness discrimination, and they acquired the reversal at a rate equal to that seen in animals with sham ablations. Rats with peristriate ablations showed no savings on the non-reversed brightness habit, and they required more extensive training than both the striate and sham groups on the reversal. These findings suggest that the frequently reported loss of a preoperative brightness habit following large posterior neocortex ablations is due to damage in the lateral peristriate neocortex rather than damage of the geniculostriate system. These results, taken with other literature, suggest an important role of the lateral peristriate neocortex in visuospatial sensory function.

Effects of bilateral and unilateral neocortical lesions on schedule-induced polydipsia in rats

Fifteen adult female rats were subjected to one of the following surgical procedures: (1) bilateral neocortical ablation; (2) unilateral neocortical ablation; or (3) sham surgery. Following recovery, all rats were tested on a fixed-time 1-min food schedule for acquisition of schedule-induced polydipsia. Contrary to a previous report by Bigler, Fleming and Shearer [1], no attenuation of polydipsia was seen in either group of rats with neocortical damage.

Forebrain catecholamine concentrations in the rat after neocortical and hippocampal lesions

Spectrofluorometric procedures were used to measure forebrain content of dopamine and norepinephrine in rats after either dorsolateral neocortical ablation, or combined neocortical-hippocampal ablations. The concentration of both of these catecholamines was significantly higher in the ablated rats than in uninjured control rats. However, there was no difference between the rats receiving only neocortical lesions and the rats with combined lesions on this measure.

Rapid forgetting of individual spatial reversal problems in rats with parafascicular lesions

Rats with posteromedial thalamic lesions were impaired in learning position reversal problems in a T maze. Test trials given after learning each reversal problem disclosed defective retention in the posteromedial thalamic group. Neither bilateral amygdaloid lesions nor unilateral neocortical ablations had any remarkable effects on learning or retention of this spatial task. Analyses of lesion placements suggest that damage to the parafascicular region is critical for the appearance of these learning and retention defects. It is proposed that the parafascicular region contributes to consolidation of spatial memory traces.

Conditioned inhibition of the nictitating membrane response in decorticate rabbits

Rabbits with substantial neocortical ablation were trained in a Pavlovian conditioned inhibition task using a light as the reinforced conditioned stimulus (CS) and the same light compounded with a tone as the non-reinforced CS. The conditioned response was the nictitating membrane response, and the unconditioned stimulus was paraorbital shock. Training began 4–14 months posteperatively. With a number of procedural variations across 4 experiments, there was little evidence of impaired conditioned inhibition by decorticates compared to control animals. These results are consistent with earlier reports on Pavlovian discrimination learning and reversal involving single-element CSs from different sense modalities. Hence, they extend the basic conclusion that neocortex is not essential for Pavlovian inhibition to the conditioned inhibition paradigm. Consideration of these findings in the light of previous investigations of conditioned inhibition in rabbits, involving mesencephalic or hippocampal lesions, supports the hypothesis that the crucial neural elements for Pavlovian inhibition may be located in the brain stem.

Differential fornix ablations and the circadian rhythmicity of adrenal corticosteroid secretion

Suction ablations of the medial or lateral fornix were performed in order to transect selectively the medial corticohypothalamic tract (mcht) which originates in the anteroventral subiculum and travels in the lateral fornix terminating in the basal hypothalamus. The circadian rhythmicity of plasma adrenal corticosteroid levels was assessed in individual animals 1--2 weeks postoperatively. Ablation of the lateral fornix disrupted the periodicity of corticosteroid secretion which is normally synchronized with the light--dark cycle, whereas medial fornix ablation or neocortical ablation caused no such disruption. Group mean levels of plasma adrenal corticoids were higher in the lateral fornix-ablated animals than in the medial fornix-ablated, neocortically ablated, or intact control animals. These findings suggest that the anteroventral subiculum is important in the regulation of adrenal corticosteroid rhythmicity, and that it exerts an inhibitory influence upon corticosteroid release.