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J Mogensen

Publications and source records attributed to J Mogensen.

At least 37 records · Page 2Linked to original sources

Synaptic reorganisation of the mediodorsal thalamic nucleus in adult rat following chronic prefrontal cortical lesions.

Chronic changes in the thalamic mediodorsal nucleus (MD) after unilateral lesions of the prefrontal cortex were studied with the aid of quantitative light, and electron microscopic immunohistochemistry. Three months after the lesions, although the size of MD ipsilateral to the lesion did not change considerably, the neuronal density was significantly reduced. Conversely, as demonstrated by quantitative electron microscopy, the density of GABA immunostained axon terminals significantly increased in the lesioned side. It is suggested, that as MD does not contain GABA cells, the reactive hyperinnervation of the MD by GABA-containing axons is of extrinsic origin. This finding is also the morphological evidence of the potential of GABA-ergic nerve cells for reactive (induced) axonal sprouting.

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Retention and relearning of spatial delayed alternation in rats after ablation of the prefrontal or total non-prefrontal isocortex.

In the present study we addressed the question whether, within the isocortex, the prefrontal area of the rat is uniquely involved in mediation of delayed alternation. In one group of rats the dorsolateral isocortex, from the dorsomedial shoulder to the dorsal lip of the rhinal sulcus was removed bilaterally in a single surgical session. In these rats delayed alternation in a T-maze was significantly less impaired than in rats with one stage bilateral removal of the medial prefrontal cortex. The prefrontal cortex seems not to depend crucially on isocortical input for its medication of delayed alternation.

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The prefrontal cortex and variants of sequential behaviour indications of functional differentiation between subdivisions of the rat's prefrontal cortex.

In two separate experiments we addressed the involvement of the rat's prefrontal cortex in mediation of the sequential ordering of the "components of behaviour". In both experiments the animals were required to operate two different and spatially distant manipulanda sequentially. While in the first experiment a light cue signalled which response would at any moment be appropriate no sensory cues offered procedural guidance during the second experiment. Both experiments focused on postoperative retention performance. In the first experiment we studied the consequences of ablation of the dorsal anteromedial cortex, the total anteromedial cortex and the suprarhinal cortex as compared to a sham operated control group. In the second experiment we compared a sham operated group to a group subjected to ablation of the total anteromedial cortex. While the proficiency of task performance was evaluated on the basis of the number of reinforcements obtained and the percentage of bar presses to be reinforced, additional analysis of behaviour included registration of the individual behavioural components and the sequential orders in which these were observed. The major findings were: (1) lesions within the anteromedial, prefrontal cortex (especially if including the ventral part of this region) are associated with significantly impaired performance of both the presently investigated tasks. (2) The demonstrated association between the anteromedial cortex and the mediation of the sequential arrangement of behavioural components does not seem to be secondary to changes in neither quality nor frequency of any individual behavioural component. (3) In the first experiment--where a cue light signalled which response would at any point in time be adequate--lesions within all parts of the prefrontal cortex (the suprarhinal as well as the anteromedial cortex) were associated with overproduction of errors, which in the behavioural sequence analysis had been characterized as "type B". We tentatively interpret such errors as reflecting a failure to utilize the visual cue offered by the signal lamp. Since lesions within all parts of the prefrontal cortex seem to be associated with "cue utilization" failures while only lesions involving the anteromedial cortex are reflected in impaired sequential arrangement of behavioural components the present studies seem to reflect a certain degree of functional specialization within the prefrontal cortex of the rat.

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Effects of chronic imipramine on exploration, locomotion, and food/water intake in rats.

Three groups of rats were subjected to 15 daily injections of imipramine (10 or 20 mg/kg) or vehicle control injections, respectively. During the treatment period, both imipramine groups failed to grow while the control group gained weight normally. Both dosages of imipramine suppressed food intake significantly, while water intake was only reduced by 20 mg/kg of imipramine and only during the first 5 days of treatment. Twenty-four hours after the last imipramine injection, the animals were subjected to a test battery designed to demonstrate potential changes in locomotion and/or exploration. While locomotion appeared unaffected by both dosages of imipramine, the group receiving 20 mg/kg of imipramine demonstrated a significantly reduced exploration. The exploration of the group receiving imipramine in the concentration of 10 mg/kg was only marginally changed. The temporal pattern of exploration of the animals receiving 20 mg/kg of imipramine revealed that chronic imipramine treatment was associated with an initial "hyperexploration" followed by an "overhabituation," resulting in an overall reduction of exploration during a 15-min period.

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Electroconvulsive stimulations, learning, and protein changes in the rat brain.

Two groups of rats were subjected to 17 training sessions on an operant task demanding the sequential operation of two manipulanda, while two other groups were left with no training experience. Within both the trained and passive groups one was exposed to a series of 12 electroconvulsive stimulations. The series of training and stimulation sessions were concurrent but arranged in such a way that at least 24 h always separated training and stimulation. Upon completion of the behavioural part of the experiment the concentrations of the marker proteins neural cell adhesion molecule (NCAM), D3, synaptophysin, and S100 were estimated in the prefrontal and occipital parts of the cortex, the hippocampus, and in the total forebrain. The electroconvulsively stimulated animals demonstrated severe impairment of learning. The pattern of marker protein concentrations indicated that acquisition and/or performance of the task and exposure to electroconvulsive stimulation were both accompanied by similar patterns of synaptic changes: an increased concentration of small synaptic vesicles in both the prefrontal cortex and the total forebrain and an increased synaptic remodulation in the prefrontal cortex.

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Absence of transsynaptic transport in cerebello-thalamo-cortical path of the rat.

Attempts to visualize the cerebello-thalamo-cortical path in the rat were made with different approaches. We tried (1) double labelling with somatopetal tracing from the motor cortex and somatofugal from the cerebellar nuclei, (2) transmembrane labelling by depositing biocytin or wheat germ agglutinin (WGA) into the motor cortex or cerebellum. WGA was either iodinated with 125I or conjugated with horseradish peroxidase (HRP). The double labelling technique showed an overlap of the tracers in the same thalamic region but no evidence of transsynaptic transport in either direction was obtained. Our results indicate a difference in the organization of this system in primates and rodents, since transsynaptic labelling in the cerebellar nuclei after injections of WGA-HRP conjugate in the monkey motor cortex has been found.

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Cortical area in the rat that mediates visual pattern discrimination.

In Experiment I, bilateral ablations of the caudolateral cortex involving Krieg's area 36 impaired discrimination of visual patterns but not delayed alternation. In Experiment II, the same type of lesions retarded postoperative learning to discriminate embedded visual patterns. In rats from the Experiment II tracers of axonal transport gave no signs of damage of the connections of the primary visual cortex. In agreement with this, Nissl stain of the dorsal lateral geniculate nuclei showed no neuronal loss or gliosis. These results suggest that caudo-lateral cortex in rats corresponds to the inferotemporal cortex of primates.

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Electrical sensitization of the meso-limbic dopaminergic system in rats: a pathogenetic model for schizophrenia.

To study whether it was possible to modify mesolimbic dopaminergic activity by intermittent electrical stimulations (IES), 44 rats were either electrically stimulated or sham-stimulated in the ventral tegmental area (VTA) once daily for 70 days. This was done through chronically implanted intracranial electrodes. The intensity of electrical stimulation was determined by the lowest current that elicited a definite motor response. Stimulated rats demonstrated a significantly potentiated behavioral response after 70 stimulations. Seven months after IES rats still demonstrated an increased sensitivity to electrical stimulations in the VTA. A new stimulation period only resulted in a modest additional fall in threshold values. There was a highly significant difference between the current needed to provoke a given response in sensitized rats and in sham-stimulated rats. The behavioral response to stimulation was suppressed both by the dopamine (DA) D2 receptor antagonists haloperidol and raclopride and by the DA D1 receptor antagonist SCH 23390. Furthermore, stimulated rats showed an enhanced response to stimulation with amphetamine and to a lesser extent with apomorphine. Between stimulation periods sensitized animals demonstrated a reduced social interaction. In conclusion intermittent electrical stimulations of the VTA resulted in a syndrome characterized by a hypersensitive response to electrical and pharmacological DA provocation combined with abnormal social interaction. This animal model has points of resemblance with recent interpretations of the DA hypothesis for schizophrenia.

Amphetamine↗

Behavioural effects of ablation of the pigeon-equivalent of the mammalian prefrontal cortex.

Six pigeons were trained to perform delayed alternation and brightness discrimination. Three of them underwent ablation of the posterodorsolateral neostriatum (PDLNS) which is believed to correspond to the mammalian prefrontal cortex. In the other three pigeons hyperstriatal lesions were induced by local injections of ibotenic acid. Ablation of PDLNS impaired performance of delayed alternation much more than did the hyperstriatal lesion. In brightness discrimination, a mild impairment occurred only on the first postoperative session and only in the PDLNS group. We conclude that the ablation of PDLNS in pigeons and of the prefrontal cortex in mammals induce similar impairments. Thus, the prefrontal cortex appears not to be a privilege of mammals, but may appear in different architectonic variants in all "higher" vertebrates.

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Contralateral somatosensory neglect in unrestrained rats after lesion of the parietal cortex of the left hemisphere.

Three groups of rats were studied: a sham operated control group and two groups in which the parietal "association" cortex had been ablated in the left and right hemispheres respectively. Twenty-four hours and 8 days postoperatively the animals were subjected to a test in which their responsiveness to lateralized somatosensory stimuli was measured while the rats were left unrestrained. Additionally, an activity cage locomotion test followed immediately upon both tests of somatosensory responsiveness. Twenty-four hours postoperatively the animals in which the parietal cortex of the left hemisphere had been ablated demonstrated a significant contralateral neglect of somatosensory stimuli while the group in which the right parietal cortex had been ablated only exhibited a non-significant tendency to a contralateral neglect. While the activity cage test did not reveal an overall difference in the activity level of the three groups the latency to initiate locomotion in the activity cage was found to be significantly decreased in both ablated groups. Eight days postoperatively both ablated groups appeared fully recovered. It is concluded that ablations of the parietal "association" cortex of the rat are associated with a syndrome of contralateral somatosensory neglect that can even be demonstrated if the animals are left unrestrained during testing.

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Retention and relearning of spatial delayed alternation in rats after combined or sequential lesions of the prefrontal and parietal cortex.

Lesions of the medial prefrontal cortex strongly impaired rats' delayed alternation behaviour in a T-maze, both when the lesion was inflicted after the initial acquisition of the task and when the lesion was added after criterion performance had been reattained following an ablation of the parietal cortex. Lesions of the parietal cortex did not impair this behaviour, either when the parietal lesion was inflicted after the initial acquisition of the task or when it was added to a prefrontal lesion after criterion performance had been reattained. Combined, one stage, parietal and prefrontal lesions did not have stronger effect on delayed alternation than did prefrontal lesions alone. These results indicate that in spite of the strong anatomical connectivity between the prefrontal and parietal "association" cortex the latter is not necessary for the recovery of delayed alternation after prefrontal lesions. In comparison with the parietal cortex, the prefrontal cortex seems to be uniquely involved in mediation of delayed alternation.

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Cortical projections of the thalamic mediodorsal nucleus in the rat. Definition of the prefrontal cortex.

Deposits of somatopetal tracers, that filled the entire dorsolateral cortex of one hemisphere, labelled only a few cell bodies in the thalamic mediodorsal nucleus (MD). Further experiments served to confirm the existence of strong projections from MD to the mesial and suprarhinal areas of the frontal cortex. Thus, only a very small proportion of the MD neurones in the rat projects outside the cortical areas described first by Leonard (1969). We conclude that at least in the rat, cortical projections of the MD are selective enough to be used as the basis for definition of the prefrontal cortex.

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Behavioural changes after ablation of subdivisions of the rat prefrontal cortex.

Sham operated controls and four groups of rats subjected to ablation of various parts of their frontal cortex were compared in food and water intake and four behavioural tasks. The ablations were aimed at removing (1) the ventral prefrontal cortex, (2) the dorsal part of the medial prefrontal cortex, (3) the total medial prefrontal cortex, and (4) the anterior dorsolateral (non-prefrontal) cortex. Only two groups had a significantly impaired food and water intake: the ventral prefrontal and the non-prefrontal anterolateral. The latter group was not adipsic. Two variants of spontaneous alternation were administered in a T-maze: a non-cued version in which both arms were grey and a cued version in which one arm was white and the other black. While all ablated groups behaved like the control group on the non-cued test, the number of perseverative responses of the total anteromedial group was significantly increased in the cued version of the test. Significant group differences could be seen neither in a test of conditioned taste aversion nor in extinction of operantly conditioned bar presses. Finally, in a vertical hole-board exploration test the only significant group difference was a prolongation of the mean visit duration of the ventrally lesioned animals in comparison with all other groups. The results of the present study further indicate functional differentiation within the prefrontal cortex of the rat.

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Fast one-step procedure for the detection of nucleic acids in situ by primer-induced sequence-specific labeling with fluorescein-12-dUTP.

We provide fast, simple, one-step procedures for sequence-specific detection of nucleic acids in situ. Tandem repeat sequences in DNA are stained within 30 min, and mRNA is stained within 2 h. The procedures are based on the incorporation of the newly available fluorescein-labeled dUTP into DNA synthesized in situ by primed in situ labeling, with denatured fragments of cloned DNA or oligonucleotides as primers. The extreme speed and simplicity of the reaction make it attractive for automatization in routine laboratory procedures and opens up new diagnostic possibilities.

DNA↗

Catecholamines and DOPAC in cortical and neostriatal regions during rats' learning of delayed alternation.

Dopamine, norepinephrine and DOPAC were measured in two cortical areas (the medial prefrontal and the posterolateral, Te2) and in the anterior and posterior neostriatum in rats which were exposed to three different experiences for three different lengths of time. One group learned delayed alternation and the two others served as controls. Throughout the training period all animals were housed in single cages. There was no significant effect of the kind of experience on any measure, but the length of exposure did affect some values: the amount of non-precursor dopamine was decreased significantly in both neostriatal samples. A significant increase of dopamine turnover and amount of norepinephrine was found in the Te2 area and in the posterior neostriatal sample. The observed changes are attributed to isolation stress. We conclude that although, as it has been described earlier, dopamine transmission is necessary for mediation of behavioural functions of the prefrontal system, it does not change quantitatively in the system during specific activity.

3,4-Dihydroxyphenylacetic Acid↗

Influences of the rearing conditions on functional properties of the rat's prefrontal system.

For a period of 42 days, starting on their 22nd day of life, rats were housed either in an 'enriched' maze-like environment in which acquisition of food and water was occasionally conditioned upon solution of spatial problems, or under 'impoverished' conditions with minimal stimulation and food and water always available. The animals were subsequently tested for initial acquisition and retention of spatial delayed alternation and a visual pattern discrimination. Finally, the effect of ablation of the medial prefrontal cortical area on the performance of the two tasks was investigated. The results showed an interaction between the rearing conditions and the order of the task presentation: the enriched environment clearly affected performance in the first task only. Thus, the group which started with delayed alternation was better in this task than any other group: the group which started with the visual discrimination performed worse in that task than any other group. The rearing conditions seemed to have no effects on the degree of impairment produced by a prefrontal cortical lesion. It is suggested that the presently used enriched environment initially biases the rats towards application of spatial hypotheses during problem solving behaviour and against the use of a visual hypothesis.

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