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H Rüthrich

Publications and source records attributed to H Rüthrich.

At least 19 recordsLinked to original sources

Activation of the dentate gyrus by stimulation of the contralateral perforant pathway: evoked potentials and long-term potentiation after ipsi- and contralateral induction.

Rats were chronically implanted with stimulation electrodes in the perforant pathway (pp) bilaterally and a recording electrode in the dentate gyrus (DG) unilaterally. Evoked field potentials (EPs) were recorded upon alternating stimulation of the pp on both sides, and long-term potentiation (LTP) was induced. Besides the EP after ipsilateral stimulation, an EP with a latency of approximately 5.5-6.5 ms was also seen upon stimulation of the contralateral pp. This potential was reversibly abolished during pentobarbital anesthesia and irreversibly after lesioning of the ipsilateral angular bundle. Paired-pulse facilitation and paired-pulse depression, depending on interstimulus interval and intensity, were also observed. Therefore, this long-latency potential could be characterized as polysynaptic and induced perhaps by transsynaptic activation via the ipsilateral entorhinal cortex. Ipsilateral tetanization induced strong E/S potentiation of both the ipsilaterally and contralaterally evoked EP, but with different time courses. Tetanization of the contralateral pp did not induce LTP of the ipsilaterally induced EP in the first 4 h. But afterwards a late and slowly developing potentiation occurred. The contralaterally induced EP also showed potentiation of the population spike, which was not immediately detectable but developed slowly over time. The results can be interpreted such that, after stimulation of the pp, the DG on the opposite side cannot only be activated via the weak crossed entorhinal projection but also transsynaptically via an entorhino/entorhinal connection.

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Development of long-lasting potentiation effects in the dentate gyrus during pentylenetetrazol kindling.

In the present study kindling was induced in rats by repeated intraperitoneal injection of pentylenetetrazol (PTZ) once every 48 h. The resulting seizure stages were registered after each PTZ application. The development of PTZ-induced kindling and the time course of possible potentiation effects in the dentate gyrus were examined. The efficacy of perforant pathway transmission to the granule cells was tested in every second kindling session by measuring the monosynaptic evoked field potentials recorded in the dentate gyrus following single test stimuli of the perforant pathway at different times after PTZ injection in freely moving animals. The data suggest that establishment of a PTZ kindling is associated with the development of long-lasting potentiation of the field potentials. After completion of kindling it was demonstrated that kindled rats also show a diminished learning performance. The relationship between the development of potentiation phenomena in hippocampal substructures and learning impairment is discussed.

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Repeated long-term potentiation induces mossy fibre sprouting and changes the sensibility of hippocampal granule cells to subconvulsive doses of pentylenetetrazol.

Electrical and chemical kindling induces sprouting of the mossy fibre system and potentiation of evoked field potentials in the dentate gyrus. It has been postulated that such changes may also be induced by repeated induction of long-term potentiation (LTP) with tetanic stimulation of the perforant pathway. LTP was induced in rats chronically implanted with stimulation electrodes in the ipsilateral and contralateral angular bundles and with a recording electrode in the ipsilateral dorsal dentate gyrus. The animals were stimulated 10 times on 10 consecutive days but with different tetanization strengths. Sprouting of the mossy fibres terminating in the CA3 region was significantly induced only in the group of 'strongly' tetanized animals, but not in that of 'weakly' tetanized animals, or in low-frequency stimulated animals. Additionally, a novel form of potentiation which was previously found in pentylenetetrazol (PTZ)-kindled animals was also observed in the group of 'strongly' and 'weakly' tetanized rats. Differences in duration of this potentiation were found between the two groups of animals tetanized with different strengths. The results further demonstrate that morphological and functional changes in the hippocampus, similar to those seen after kindling, can also occur in an activation paradigm leading to long-lasting synaptic plasticity but not accompanied by seizure activity.

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Effects of piracetam on pentylenetetrazol-kindling development, hippocampal potentiation phenomena and kindling-induced learning deficit.

Kindling is a generally accepted model for studying epilepsy development in the context of overexpression of processes of neuronal plasticity. In previous studies we have shown that establishment of kindling by repeated application of subconvulsive doses of pentylenetetrazol (PTZ) also led to marked changes in hippocampal excitability and an impairment in learning behaviour. With the intention of further investigating the relationship between kindling development, kindling-induced changes in excitability and learning deficits, rats were chemically kindled under pretreatment with the nootropic drug piracetam. Furthermore, we tested acute piracetam effects on developed kindling seizures, the learning deficit and potentiation effects. At the investigated dose piracetam did not influence the kindling development. The kindling-induced potentiation of hippocampal field potentials was significantly diminished in piracetam-pretreated rats. Piracetam acutely injected completely antagonized this potentiation effect. Piracetam brought about a significant improvement in impaired learning performance in rats pretreated during kindling induction and acutely injected before the learning experiment, respectively. Possible correlations between the suppressing of the kindling related potentiation in hippocampal structures by piracetam and its beneficial effect on learning impairment are discussed as antagonizing overexpression of potentiation in the course of kindling.

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Effects of nicardipine, an antagonist of L-type voltage-dependent calcium channels, on kindling development, kindling-induced learning deficits and hippocampal potentiation phenomena.

Kindling is considered to be a useful experimental model for investigating drug effects on the convulsive component of epilepsy and related alterations at the behavioural level. It was demonstrated that pentylenetetrazol (PTZ)-kindled rats show diminished learning performance in shuttle-box training. We used this model to study the influence of nicardipine, an antagonist of L-type voltage-dependent calcium channels, on kindling seizure development as well as related learning impairments. Additionally, we tested the influence of nicardipine on kindling-induced potentiation, a special form of long-term enhancement of evoked potentials in the dentate gyrus after kindling. Therefore, monosynaptic evoked field potentials in the dentate area upon test stimuli to the perforant pathway were recorded in freely moving kindled and control rats at different times after injection of PTZ. The results indicate that the blockade of L-type voltage-dependent Ca2+-channels during the kindling procedure attenuates PTZ-kindling, antagonizes a kindling-induced learning deficit in an active avoidance test and decreases a novel form of kindling-related potentiation, the long-lasting amplitude enhancement of the monosynaptic evoked field potential in the dentate gyrus after injection of a small test dose of PTZ. This potentiation can also be prevented in kindled animals by nicardipine injection in an acute experiment.

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Do dentate area transplants take the function of damaged dentate area neurons in the rat brain after having replaced them?

Colchicine eliminates selectively dentata area granular cells after topical microinjections. In rats treated this way it was impossible to evoke field potentials by perforant parth stimulation and the animals were unable to learn if perforant path stimulation was used as conditioned signal. After colchicine lesion neonatal dentate area tissue was grafted into the lesioned region. Between 4 and 10 weeks after grafting it was again possible to evoke potentials after perforant path stimulation and the rats were able to learn, whereas colchicine-treated rats without grafts failed. The histological investigation showed well on grown neurons within the grafts. The grafts were well integrated. It was shown that the mossy fibers from the grafts innervated the deserted CA3 sector, and that the grafted neurons were innervated by nervous fibers from the recipient brain. It can be supposed that the granular cells from the grafts were able to taken the function of the damaged granular cells of the colchicine treated dentate area.

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Orotate improves memory and enhances synaptic long-term potentiation in active avoidance behaviour in rats with perforant path stimulation as the conditioned stimulus.

Male Wistar rats were trained in an active avoidance task with stimulation of the perforant path with impulse trains of 15 Hz as the conditioning stimulus. Immediately after the first training session, methylglucamine orotate (225 micrograms), a memory improving drug, was injected intraventricularly. The retention of the learned behaviour was determined on the following day in a relearning session. Field potentials evoked in the dentate area by test stimuli from the perforant path electrode were recorded at different times after learning and relearning sessions to determine whether there were functional changes in the perforant path-granular cell synapses, which are involved in the conditioning pathway. Untreated control animals exhibited a so-called 'postconditioning potentiation', expressed as a long-lasting increase of both the excitatory postsynaptic potential (EPSP) and the population spike of the granular cells of the evoked test potentials. This finding reproduces previously published results. Methylglucamine orotate-treated rats showed significantly more conditioned reactions in the relearning sessions compared with untreated controls and a significantly more pronounced potentiation of the population spike, whereas the postconditioning potentiation of the field EPSP remained unaffected by the treatment. When both the control animals and the methylglucamine orotate-treated rats were divided into subgroups of good and poor learners according to their learning scores from the first training session, differences between the effect of the drug became evident. In good learners, the treatment with methylglucamine orotate after the learning session slightly, but significantly, improved retention compared with that of untreated good learners.(ABSTRACT TRUNCATED AT 250 WORDS)

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Incorporation of [3H]fucose in rat hippocampal structures after conditioning by perforant path stimulation and after LTP-producing tetanization.

The contribution of glycoprotein synthesis to functional synaptic changes and to the formation of memory traces was investigated by autoradiographic determination of the incorporation of [3H]fucose into the hippocampal structures of rats. In the first experiment, the fucose incorporation was measured after induction of post-tetanic long-term potentiation (LTP) in granular cell synapses by repeated tetanization (200 cps) of the perforant path, and after stimulation of this hippocampal input by the same number of impulses with very low frequency (0.2 cps) not producing LTP. In the second experiment, the incorporation of fucose was determined after an active avoidance training using the stimulation of the perforant path by impulse trains of 15 cps as conditioning stimuli, and after a session of corresponding unpaired stimulations of the perforant path. Unstimulated animals were used in both experiments to measure the basal glycosylation. LTP-producing tetanization resulted only in a slight increase of incorporation into the ipsilateral hippocampal structures without significant differences to similar changes after the corresponding control stimulation with single impulses. After a session of unpaired stimulation of the perforant path with impulse trains of 15 cps only slight and inconsistent changes of incorporation occurred in the hippocampus too. However, after conditioning by the corresponding perforant path stimulation as conditioned stimulus, considerable increases of incorporation were observed in all structures of the ipsilateral hippocampus, when compared to the unpaired control stimulation. An enhanced labeling occurred also in some structures of the contralateral hippocampus mainly receiving commissural inputs. The results suggest again, that the activation of one single hippocampal afferent, even if producing LTP, would not be sufficient to induce an increased glycosylation of neuronal proteins. The increase of glycoprotein formation seems to require the convergence of several inputs, which can be assumed to occur during learning. Therefore, LTP of a single synaptic population seems not to represent the complete long-lasting memory trace, but only one of its components, or a preceding transient storage mechanism.

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Colchicine-induced lesion of rat hippocampal granular cells prevents conditioned active avoidance with perforant path stimulation as conditioned stimulus, but not conditioned emotion.

Successful acquisition of active avoidance by rats with low frequency (15 cps) stimulation of the perforant path as a conditioning stimulus is correlated with a slowly developing long-term enhancement of perforant path-granular cell synapses. After selective destruction of granular cells of the stimulated side by unilateral microinjection of 1.6 micrograms/0.2 microliter colchicine into the dentate area, field potentials could no longer be evoked by test stimuli and animals subsequently failed to acquire the conditioned active avoidance with perforant path stimulation as a CS. However, colchicine-treated animals showed the same development of conditioned emotional responses as saline controls and they could also successfully be conditioned with light and tone as the CS. These results suggest that the granular cells are necessarily involved in the conditioning pathway for the active avoidance with perforant path stimulation as the CS. Other targets of the perforant path, e.g., ipsi- and contralateral CA1 pyramidal cells and contralateral granular cells, or antidromic activation of the entorhinal cortex seem an insufficient substitute for granular cells in the pathway for this conditioned active avoidance, but would probably participate in the conditioned emotional responses. The results additionally support our hypothesis, that post-conditioning LTP in granular cell synapses contribute to the acquisition and/or the storage of a memory trace.

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[The effect of the systemic and intraventricular application of orotic acid on monosynaptic evoked potentials in the dentate gyrus in free-moving rats].

In 20 freely moving Wistar rats the influence of systemically and intraventricularly applied orotic acid derivatives on monosynaptically evoked field potentials registered in the dentate gyrus on the stimulation of the medial entorhinal cortex was investigated. Both, methylglucamine-orotate and tris-orotate led to an increase of the amplitude of the population spike. The slope function of the field EPSP, however, remained unchanged. The effect has been observed to begin 2 h after application and had a duration of 6-10 h. The data obtained in a monosynaptic pathway targeting on a brain structure which is known to play a crucial role in memory formation support earlier findings of a transient effect of orotic acid on cerebral excitation processes. An influence on mechanisms of spike generation or other postsynaptic membrane processes might be assumed.

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Autoradiographic assessment of [3H]proline uptake by neurons of epileptogenic mirror focus.

Epileptogenic mirror focus was produced in the left parietal area of the rat brain by cobalt implantation into the contralateral hemisphere. On the 14th day after cobalt implantation [3H]proline was injected into both experimental and control rats (without cobalt). The incorporation of [3H]proline in neurons of layers III and V of the parietal brain cortex and neurons of the nucleus lateralis thalami was investigated by the autoradiography technique. A statistically reliable increase in [3H]proline uptake was observed in neurons of layer III (31%) and in neurons of layer V (41%) of the epileptogenic mirror focus. The other neuronal types revealed no reliable changes. The morphological and functional aspects of the altered protein metabolism during epileptogenesis are discussed.

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Monosynaptic activation of the hippocampus as a conditioned stimulus: behavioral effects.

The aim of the present study with rats was to show that electrical stimulation of a monosynaptic pathway, whose high plastic potency is well-known, can serve as a conditioned stimulus (CS) in a learning paradigm. Using chronic rats, stimulation of the perforant pathway, which activates the entorhinal cortex input to the dentate gyrus of the hippocampus, was used as the CS in a footshock motivated two-way avoidance task (shuttle box). Among the different stimulation parameters tested, only trains of at least 15 Hz were shown to be effective as a CS, whereas the application of single impulses with a frequency of 1,7 Hz did not result in the establishment of conditioned behavior. Using the 15 Hz-paradigm, in "good learners," the development of reliable conditioned responses started at the end of the first training session (40 trials) and become fairly stable during a further training session, given on the following day. The application of stimulation trains with 100 Hz as a CS led to the development of a high rate of conditioned responses, however, there was also a high level of intertrial reactions. Considering the critical importance of the frequency parameters of the perforant pathway stimulation for the development of conditioned behavior the possible involvement of hippocampal long-term potentiation in behavioral plasticity is discussed. Additionally, it is concluded that this new learning paradigm offers the advantage of concurrent analysis of plastic processes both at the behavioral level and at the level of the synaptic population.

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[Relationship between the changes of spontaneous activity and responses of cortical neurons under microiontophoretic administration of glutamic acid].

In neurons of the gyrus sigmoideus posterior of cats, the influence of microiontophoretic application of varying doses of glutamic acid upon the reaction of those neurons to stimulations of the ischiadic nerve and clicks, and the changes of spontaneous activity were studied. The application of glutamic acid led, in 97% of the 90 neurons studied, to a dose-dependent increase in the mean firing rate; in 34% of neurons, to effectuation of click responses, and affected the reaction to stimulation of the ischiadic nerve to a varying extent. With increasing doses of glutamic acid, there was a linear correlation between the logarithm of spontaneous activity and the activity of excitatory responses with considerable differences in the steepness of the resulting straight lines for the individual neurons.

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