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Biomedical subjects

F Klingberg

Publications and source records attributed to F Klingberg.

At least 37 records · Page 2Linked to original sources

Visually evoked responses in the primary cortex of rats are permanently changed by early postnatal treatment with monosodium-L-glutamate.

13 rats of the Long-Evans strain were treated from the first to the eleventh postnatal day (pd) with daily subcutaneous injections of 4 mg/g body weight monosodium-L-glutamate (MSG) in aqua dest. Further 13 rats were used as controls and received isotonic NaCl-solution on the same days. When rats were four months old, epidural electrodes were implanted on the visual cortex to investigate averaged evoked potential by flash (VEP) and by click stimuli (AEP). All VEP components of MSG rats were changed in their amplitudes and peak times. Mainly the early components were strongly reduced and irregularly split. AEP in the visual cortex of MSG rats were also significantly changed. Photically evoked afterdischarges (AD) were not statistically altered. The evoked potential analysis revealed great interindividual heterogeneity and their topographical distribution was also strongly modified. The postmortem macroscopic inspection of the brains resulted in strong atrophy of the optic nerves and the chiasma. During two-month observations we observed no restoration of the evoked potentials to normal values.

Acoustic Stimulation↗

Permanent changes of the visually evoked responses in the superior colliculus after early postnatal treatment with monosodium-L-glutamate.

10 rats of the Long-Evans strain were treated from the first to the eleventh postnatal day (pd) with daily subcutaneous injections of 4 mg/g body weight monosodium-L-glutamate (MSG) in aqua dest. 10 rats were used as controls and received isotonic NaCl-solution on the same days. When rats were 4 months old, electrodes were implanted in different depths of the superior colliculus (CS) to investigate averaged evoked potentials by flash (VEP) and by click stimuli (AEP). The VEP in the superficial layers of the CS of MSG rats were strongly reduced in their amplitudes and irregularly shaped with the most prominent result that the primary negative component N28 was missing. The deeper recordings were made, the less this polarity-reversed primary component was affected with still significant amplitude reduction in the deepest layer. Shape and peak times of the AEP from the same electrodes in different depths were not significantly changed. However, the amplitudes of the early negative-positive and the second negative-positive deflections were enhanced in all MSG treated rats, and the amplitude proportions between VEP and AEP were in favour of AEP, in contrast to the controls. Heteromodal interactions of paired click and flash with an interval of 100 ms resulted in nearly total suppression of the VEP, in contrast to controls in which VEP were rather uninfluenced by the preceding click. Also the behaviour-dependent reduction of VEP during grooming and exploratory behaviour was much stronger in MSG treated rats compared with controls. The evoked potential analyses revealed greater interindividual heterogeneity of VEP in MSG treated rats than in controls.

Acoustic Stimulation↗

Active avoidance is permanently abolished after lesions of the nucleus interpeduncularis in rat.

Active avoidance learning, retention and relearning were investigated before and after lesions of the interpeduncular nucleus (IP) of rat in a Y-maze and a jump test box. Preoperatively learnt active avoidance was abolished after the lesions and rats were not able to relearn it. Unconditioned escape responses remained unchanged in the Y-maze. Postoperative avoidance learning was impossible. Brightness discrimination in a goal alternation paradigm was learned or relearned, respectively, after IP lesions. The IP rats were hypoactive and showed diminished exploratory activity but had unchanged escape speed. The IP is evidently enclosed in a network controlling avoidance behaviour.

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Lesions of median raphe nucleus disrupt active avoidance behaviour.

Active avoidance of eighteen adult male hooded rats was investigated in an Y-maze and a jump test before and after small symmetric lesions of the median raphe nucleus (n. centralis superior, CES). Formation of conditioned avoidance responses (CAR) was impossible without preoperative experience. Retention of preoperatively learnt CAR was almost zero after lesions. Relearning was strongly delayed but possible in the jump test, however, not in the Y-maze. CES rats did not reach criterion in brightness discrimination. On the other hand, their spontaneous behaviour in the open field remained unchanged.

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Behaviour-dependent changes of the acoustically evoked potential in the frontal cortex of the freely moving rat and modulation by electrical basal forebrain stimulation.

The behaviour-dependent and nucleus basalis magnocellularis (basal forebrain; bf) stimulation-induced modulatory influences on acoustically evoked potentials (AEP) in the medial frontal cortex (FC) of freely moving rats are described and compared. Bipolar stimulating electrodes were implanted within the bf and recording electrodes on the frontal cortex, area 10, the somatosensory cortex, area 3, the olfactory bulb, and in the nasal bone. Electrical single impulses with increasing intensities were applied within the bf 100 ms before or simultaneously with the click. The configuration of the FC-AEP and amplitudes of its components depending on spontaneous changes of the behavioural state. During grooming and exploration the prominent alterations in comparison to relaxed wakefulness are reductions of the amplitudes and shortening of the peak times of the AEP components. The bf stimulation simultaneously with the click caused amplitude reductions of all FC-AEP components. When the electrical stimuli were applied 100 ms before click, an amplitude reduction of the N21 component correlated with a shorter peak time of the N60 component was observed. These modulations are similar to AEP configuration during a certain type of spontaneous exploration. The bf-induced modulatory influences on the acoustic information processing within the FC are different immediately after bf stimulation and 100 ms later.

Acoustic Stimulation↗

Learning and retrieval are impaired after lesions of the ventral part of rat's nucleus reticularis pontis oralis.

Adult male hooded rats of the Long-Evans strain were investigated before and after lesions of the ventral nucleus reticularis pontis oralis (vRPO) in an open field test (OF) and in a Y-maze. The OF and the neurological findings were scarcely changed. Startle responses were strongly reduced and also horizontal head and body turning in the OF were significantly reduced. The retention of Y-maze avoidance tasks was reduced and relearning of the tasks relatively slow. Brightness discrimination remained unaffected by the lesion. The postoperative active avoidance learning of a new task in the jump test box was impossible. Postoperative learning of a thirst-motivated labyrinth task was significantly retarded compared with unoperated control rats. The vRPO lesion syndrome is quite different compared with 1 mm more dorsal (dRPO) and 1 mm more posterior (vRPC, dRPC) placed lesions and underlines the hypothesis of the functional heterogeneity of the pontine reticular formation.

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Evidence for cholinergic participation in frontal cortical potentials evoked by single impulse stimulation in the locus coeruleus area of freely moving rats.

Single impulse stimulation in the area of locus coeruleus (LC) in freely moving rats evokes bilateral symmetrical potentials (EP) in the frontal cortex. Threshold intensity for this potential was higher when the stimulus electrode was in the LC than in the cholinergic dorsal parabrachial nucleus lateral of LC. Amplitudes and peak times of this EP were constant during relaxed wakefulness, exploratory behavior and unaffected by beta-blockade (propranolol, 2.5 mg/kg i.p.). Their amplitudes were strongly decreased and the peak times of later negativity (N50) were prolonged during slow wave sleep and by muscarinic blockade with scopolamine (0.5 mg/kg i.p.) which induced active behavior and synchronized EEG. These data suggest a direct participation of cholinergic structures in cortical potential evoked by electrical LC stimulation. Relations between stimulus effect and behavior regulating systems are discussed.

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Modulatory effect of locus coeruleus stimulation on visually evoked potentials in freely moving rats.

Interactions between light-flash stimulation and electrical single impulse stimulation of locus coeruleus (LC) were investigated in 9 freely moving rats with chronically implanted electrodes during different behavioral states. The interaction of both showed different immediate and long-lasting effects. Simultaneous visual and electrical stimulation caused a clear decrease of trigger rate of photically evoked after-discharges from 60% to 15% and a reduction of the early primary component of visually evoked potentials (VEP) in area 17 compared with the values without LC stimulation during relaxed wakefulness (RW). On the contrary, the simultaneous LC stimulation was ineffective during exploratory behavioral states (E). At 100 ms stimulus interval and more there was no detectable LC stimulus effect on VEP components during RW, whereas the LC stimulation under beta-blockade (2.5 mg/kg propranolol i.p.) during RW-like behavior clearly reduced the early VEP component to 75% compared with values without LC stimulation. On the other hand, LC stimulation facilitated mainly the primary VEP component to about 160% during E compared with the flash response alone. This effect was observed from 100 to 300 ms after LC stimulus and was unaffected by muscarinic blockade (0.5 mg/kg scopolamine i.p.). We conclude from these data that the short-time effects are comparable with the influence of spontaneous behavioral activation and probably result from a costimulation of cholinergic neurons around LC, whereas the long-lasting effects may be attributed to the influence of noradrenergic LC cells. The noradrenergic-dependent facilitation of early VEP component counteracts the cholinergically-induced reduction.

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The mesencephalic reticular formation as a link in the cortical control of exploratory and goal-directed behaviour.

The general accepted concept about the MRF as an unspecific ascending activating system concerns only one of its multiple functions. Investigations on more than 100 hooded rats of the Long-Evans strain with small bilateral symmetric lesions in dorsal, central and ventral subnuclei of the MRF brought out the following results pointing to further important functions: 1. Each lesion type produced a different syndrome of parameter changes of the spontaneous open field behavior with some common tendencies of reduced ambulatory and exploratory activities. 2. Visual placing responses were strongly reduced or totally abolished after lesions without tendencies of recovery. 3. Changes of locomotion and muscular tonus were quite different or even opposite in dorsal, central and ventral types of lesions. 4. In four tasks of postoperative active avoidance acquisition or retention and performance of preoperatively learned tasks the impairments were different related to the lesion type including a different loss in brightness discrimination. The results support the hypothesis that MRF subdivisions participate differently in information selection, tuning and coupling information with goal directed movements of different type. Lesions severely disturb the proper use of some information for a cue, especially visual cues when they are in the anterior part of the mesencephalon.

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Electrical stimulations of the basal forebrain and the nucleus cuneiformis differently modulate behavioural activation of freely moving rat.

Differences in inducing behavioural activation of two different cholinergic brain regions, the basal forebrain (nucleus basalis magnocellularis) and the mesencephalic nucleus cuneiformis were investigated in freely moving rats with electrodes in the hippocampus, the frontal cortex and olfactory bulb. Serial electrical stimulations with increasing intensities, a duration of 1 s and frequencies of 100 and 10 cps and single impulses were applied within both cholinergic regions. After lesions of the stimulated sites the tests were repeated. Serial stimulations of both cholinergic structures increased respiration rate, motor activity, and the trigger rate of slow hippocampal rhythm (theta rhythm) differently. However, the increase of these parameters of behavioural activation by stimulation of the basal forebrain were probably unspecific effects accompanying general behavioural activation because they remained unaffected by lesions of the stimulated sites. The nucleus cuneiformis modulates specifically respiration rate and motor activity. The duration of the behavioural activation by nucleus cuneiformis stimulation was longer compared with basal forebrain stimulation, and it was shortened by lesion of the nucleus cuneiformis. The frequency of the evoked slow hippocampal rhythm was higher with nucleus cuneiformis stimulation. The results indicate that the nucleus cuneiformis is a more homogeneous structure with regard to the modulation of these behavioural parameters whereas the basal forebrain showed more functional heterogeneity with 100 cps stimulation in all investigated parameters, with 10 cps stimulation only in the trigger rate of the slow hippocampal rhythm and the duration of evoked motor activity despite equal effects on the respiration rate and the intensity of motor activity. Functional heterogeneity was also observed in the induction of directed movements whereas with nucleus cuneiformis stimulation the directions of evoked movements were rather equal. Excessive behavioural excitement was only inducible with nucleus cuneiformis stimulation.

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Visually evoked potentials are differently modulated by the basal forebrain and the nucleus cuneiformis of freely moving rat.

Different modulatory influences on visually evoked potentials (VEPs) of freely moving rats from two different cholinergic brain regions, the basal forebrain (bf, nucleus basalis magnocellularis) and the mesencephalic parabrachial nucleus cuneiformis (Cnf) are described. Bipolar stimulating electrodes were implanted in both regions and recording electrodes on the visual cortex, the frontal cortex, the olfactory bulb, and in the nasal bone. Serial electrical stimulations with increasing intensities, a series duration of 1 s, and frequencies of 100 and 10 cps, and single impulses were applied within both cholinergic regions 100 ms before light flashes. Lesions of the stimulated sites were produced to test whether modulations disappear. The bf revealed heterogeneous effects on the evoked potentials depending on the stimulation modes and on the electrode localization inside the bf whereas the Cnf modulated the evoked potentials rather uniformly. All stimulation modes in the Cnf reduced the N 30-amplitude of the primary VEP in the visual cortex simultaneously with a decrease of their peak times, and reduced the trigger rate of photically evoked afterdischarges (PhAD). 100 and 10 cps stimulation of the Cnf decreased also the PhAD amplitude and the number of PhAD per flash when stimulation intensity was above the threshold of behavioural activation. The bf stimulation with 100 cps modulated all investigated parameters differently in their quantity: with 10 cps stimulation VEP amplitude and PhAD trigger rate were differently modulated. Single impulses within the bf 100 ms before flash were ineffective on the evoked potentials. No peak time alterations of the VEP were evoked with 10 cps stimulation within the bf in contrast to Cnf stimulation. The bf seems to be heterogeneous in its physiological effects on the visual cortex.

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Lesions of the caudal pontine reticular nucleus reduce spontaneous behavioural activity of rats differently in dorsal and ventral parts of the nucleus.

Four groups of 8 adult male hooded rats of the Long-Evans strain were investigated before and after lesions of the dorsal or the ventral subdivisions of the caudal pontine reticular nucleus (RPC) in an open field test (OF) and in a neurological test program. After dorsal (d) RPC lesions all labyrinthine reflexes were extremely slowed, tactile and visual placing responses strongly reduced and the startle reflex abolished, whereas ventral (v) RPC lesions did not alter the neurological status. The dRPC rats showed strongly reduced drinking from water bottles, did not eat pellets in their home cages and lost 5% of their body weight per day. This could be prevented by a supply with a cornflake pap. The ventral RPC lesion revealed no influence on food and water intake. Ambulatory activity in the OF was strongly reduced by dorsal lesions but not by ventralones. The habituation quotient increased only after ventral RPC lesions. Both lesion types increased the duration of immobilization. Exploratory activity was also reduced after both lesion types, but significantly stronger after dorsal lesions. In a centrophobia test the dRPC rats were 6 times slower than before lesion, whereas vRPC rats remained unchanged compared with their preoperative values. The negativism-test revealed strong enhancement after dRPC lesions, but not so strong after vRPC lesions. The results indicate specialized subdivisions of the pontine reticular formation controlling differently spontaneous behaviour.

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Learning and retention of active avoidance are differently impaired after dorsal and ventral lesions of the nucleus reticularis pontis caudalis of rats.

Four groups of 8 adult male hooded rats of the Long-Evans strain were investigated before and after bilateral symmetric lesions of the nucleus reticularis pontis caudalis (RPC) in a Y-maze and in a jump test box. After dorsal (d) RPC lesions the retention of preoperatively learnt simple tasks in the Y-maze or in the jump test was not impaired whereas brightness discrimination in the Y-maze was neither retained nor relearned. Postoperative acquisition without preoperative experience was impossible for dRPC rats in any of the tests. After ventral (v) RPC lesions there was no retention of active avoidance response in the Y-maze but rather normal retention of the jump test performance. The retention of brightness discrimination, however, was not impaired in the Y-maze after vRPC lesions. The relearning of the impaired active avoidance in the Y-maze was impossible for vRPC rats; though these rats showed intrasessional improvement, there was no retention between sessions. After retention of the simple jump test task the vRPC rats were not able to learn a go/no-go task in the jump test box. Acute extinction to the non-reinforced 2.5 KHz tone was prolonged. Intertrial responses in the jump test were reduced to zero after dRPC lesions, but significantly enhanced after vRPC lesions. The results indicate that CAR response initiation was reduced after dRPC lesions, but in vRPC rats the suppression of incorrect responses was reduced in the jump test. The lesions differently impair the control of learnt motor programs.

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Active avoidance is impaired correlated with changes of spontaneous behaviour after lesions of the lateral parabrachial nucleus of rat.

Open field (OF) behaviour, active avoidance (CAR) acquisition and the neurological status of 14 male hooded rats of the Long-Evans strain were compared before and after bilateral electrocoagulation of the lateral parabrachial nucleus (PB1). The PB1 lesion syndrome was characterized by significantly more square crossings in spite of more grooming and significant longer duration for immobility in the OF. The exploratory activity was strongly reduced. PB rats moved more quickly, whenever they performed ambulation. The habituation quotient for ambulatory activity was insignificantly decreased but for exploratory activity significantly increased. PB rats were able to reproduce preoperatively learnt CAR in the Y-maze but not in the jump test and could not postoperatively acquire a new avoidance stereotype. The results indicate an important participation of PB1 in response selection and CAR acquisition.

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Lesions of anterior thalamic nuclei impair acquisition of new and changing of preoperatively learnt active avoidance stereotypes.

Six-month-old male Long-Evans rats reproduced their preoperatively learnt active avoidance responses (CAR) in a Y-maze and in a jump test box after bilateral symmetric lesions of thalamic anterior ventral (AV) and anterior medial (AM) nuclei without significant changes. However, when the test sequence was changed in a way that transitions from high success probability (low error probability) to low success probability (high error probability) were taken into account, then problems with time limit and increased punishments were not overcome by lesioned rats. Transitions in the opposite direction were better mastered. All AV-AM rats were unable to acquire a new CAR stereotype in a W-like maze in which the first phase had a low success probability. Rats without lesions were rarely influenced by various test sequences. The lesioned rats showed purely arrest behaviour and did not develop learned helplessness in successless sessions and were transiently hyperactive in the open field test. The data support the hypothesis that the anterior thalamic nuclei as part of the Papez circuit participate in the analysis of success probability and preferent consolidation of correct responses, when stereotype behaviour has to be changed.

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Ontogenetic development of avoidance learning in rats after eye opening.

Five male and one female group of 8 pups were selected from 8 liters on the second postnatal day and returned to 6 dams. The animals were investigated in two subsequent tests; first, in a peripheral field avoidance test using a 60 x 75 x 22 cm open field subdivided into 20 equal squares of 15 x 15 cm with separate floor grids for electrical punishment and, second, in a W-like maze with a start arm falling into a common alley from which left and right each two goal arms branched off. Four qualities were measured in the first test: finding out that only central fields remained unpunished; the stay duration in central fields indicating passive avoidance; the response to a conditioned stimulus, when they entered peripheral fields indicating active avoidance; the quality of extinction. The differences of these qualities changed significantly from week to week as the acquisition speed and the consolidation increased, the extinction was rapid in the third week, very slow in the fourth week and adult-like in the fifth week. The self-chosen strategy of pups showed dominance of escape with subsequent motor inhibition in the third week, dominance of trials and active avoidance in the fourth week, dominance of passive avoidance in the fifth week. We found no difference between males and females, or between blind and control rats. The W-maze test revealed additionally that reversal learning from left goal to right goal was still difficult in the fourth week and that brightness-cued alteration of goals in which wrong choices were punished when a time limit was overcome could not be learned before the sixth week and not consolidated before the end of the seventh week. The results suggest that various brain processes are involved in the development of avoidance and learning strategies which mature unevenly and reach their peaks at different ages.

Aging↗

Postnatal application of p-chloroamphetamine or fenfluramine reduces response selection during early ontogenetic development of rat avoidance behaviour.

The influence of one single intraperitoneal application of 50 mumol/kg fenfluramine (FF) or 50 mumol/kg parachloroamphetamine (PCA), respectively, on the 8th postnatal day upon avoidance learning in the early ontogenesis was compared with vehicle-injected controls (NaCl solution). The intoxicated groups were unable to learn a self-shaped avoidance behaviour in a peripheral field avoidance test. They did not find out during the third postnatal week that only central fields of an open field remained unpunished; escape responses along walls were not inhibited in favour of escape into central fields as in controls. The passive avoidance component which is expressed by increasing stay duration in central fields was not developed in FF and PCA rats. The active avoidance component expressed by CS-induced escape before UCS did also not increase in the intoxicated rats. There were no differences of passive avoidance between groups, however, in the fourth week. In the W-maze test after weaning differences between intoxicated groups and controls were evident in the first session and when the schedule was changed. In the reversal learning session the intoxicated groups made more errors. The results support the view that serotoninergic neuron groups participate in the inhibition of incorrect responses and differentiation learning. This early postnatal deficiency may be partly compensated in further development.

Aging↗

Lesions in the mesencephalic reticular formation change open field and thirst motivated labyrinth behaviour of rats.

Open field behaviour and thirst motivated running through two labyrinth variants were compared before and after bilateral symmetric lesions of the anterior part of the dorsolateral parabrachial nucleus (PBl) and in the anterior mesencephalic area cuneiformis (CU), both n = 9, on 4-month-old male Long-Evans rats. CU-rats were characterized by abolished visual placing responses, aphagia or hypophagia which was limited up to the 15th postoperative day, ambulatory hyperactivity, reduced climbing and grooming, but enhanced rearing. Their preoperatively learnt thirst motivated labyrinth passage remained unimpaired but their drinking behaviour was persistently changed. They interrupted drinking several times and regularly did not empty the cups. Thirst motivation was evidently reduced after CU-lesions. PBl-rats were ambulatory hypoactive and slowed with accelerated habituation, reduced climbing and changed incline-plane behaviour. A slight hypophagia was generally overcome after the 5th postoperative day. Labyrinth performance of PBl-rats was evidently changed with significantly slower runs and impaired differentiation of the second labyrinth type in which passage duration, errors and even duration of licking were enhanced. Water intake was less reduced than in CU-rats. Both nuclei include parts of the "mesencephalic locomotor region", but contribute differently to the regulation of spontaneous and goal-directed behaviour.

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