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T Ott

Publications and source records attributed to T Ott.

At least 73 records · Page 4Linked to original sources

Functional plasticity in two afferent systems of the granule cells in the rat dentate area: frequency-related changes, long-term potentiation and heterosynaptic depression.

Monosynaptic evoked field potentials (MEFP) were recorded in the dentate gyrus of male Wistar rats upon stimulation of either the perforant path or the commissural system. While the perforant path potential exhibited in acute experiments a clear reversal point of the field excitatory postsynaptic potential (EPSP) and population spike when protruding the registration electrode from the hippocampal fissura to the hilus of the dentate gyrus, the simultaneously registered commissural potential elicited by stimulation of the contralateral hilus showed no reversal of the negative monophasic wave but merely an amplitude maximum 40 microns above the reversal point of the perforant path potential. Frequency-related changes of the MEFPs during short tetanic stimulation with 15 Hz both in acute and chronic experiments, revealed differences in the properties of the input systems in that the commissural potential exhibited a clear frequency potentiation whereas the perforant path potential showed frequency depression. Pronounced long-term potentiation of the perforant path potential induced by 4 trains of tetanizing stimuli and lasting up to 72 h was accompanied by a long-term heterosynaptic depression of the commissural potential for up to 7 days after tetanization. Both the different frequency-related changes of the inputs and the extremely long duration of the heterosynaptic depression are discussed with respect to their proposed functions in the mechanisms of functional plasticity.

Animals↗

The duration of long-term potentiation in the CA1 region of the hippocampal slice preparation.

The duration of long-term potentiation (LTP) of the monosynaptic excitatory Schaffer collateral-commissural input to hippocampal neurons of the CA1 region was examined in the in vitro slice. Relatively stable evoked potentials were obtained under conventional perfusion conditions at least for 10 hours. Tetanic stimulation (100 Hz, 1 sec) increased the population spike (pop-spike) amplitude by about 150% and the slope of the field-EPSP by about 30% over the pre-LTP baseline, whereas the latency and peak latency of the pop-spike decreased. In comparison to control experiments (same number of stimuli at 0.2 Hz) the differences were statistically significant for 2 hr (field-EPSP) and for greater than or equal to 10 hr (pop-spike), respectively. Repeated tetanization (3 X 100 Hz/1 sec), however, substantially prolongs EPSP-LTP (greater than or equal to 10 hr) and doubles the approximated half-life of pop-spike LTP. The threshold current intensity to elicit pop-spike responses decreased after the induction of LTP. Furthermore, the smaller field-EPSP values necessary to evoke near-threshold pop-spikes demonstrate an E-S potentiation (left-shift) at least in the low-intensity range. While the total duration of potentiation of the different parameters has not been determined, all the above mentioned effects could be observed at least 10 hr following the repeated tetanization. It is proposed that the slice preparation is suitable for the investigation of mechanisms of a postulated late phase of LTP if appropriate conditions are used.

Animals↗

Effects of beta-casomorphin on dentate hippocampal field potentials in freely moving rats.

Intracerebroventricular administration of 166 nmoles of the exogenic opioid beta-casomorphin (5) produced a potent and reversible depression of the compound action potential evoked in dentate granule cells by stimulation of the medial perforant path, whereas the extracellularly recorded excitatory postsynaptic potential is left unchanged. This in vivo effect of beta-casomorphin was obviously different from those observed previously in the CA 1 region in hippocampal slice experiments. The results suggest that more than one opioid mechanism determines the granule cell excitability. Some of the possible mechanisms involved in the effects of beta-casomorphins in the hippocampus are briefly discussed.

Animals↗

[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.

Animals↗

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.

Animals↗

Effect of the memory-improving substance methylglucamine orotate on paradoxical sleep in rats.

The effects of methylglucamine orotate (MGO) were studied on polygraphic sleep recordings in rats for 8 h per day between 8 a.m. and 4 p.m. MGO (225 mg/kg) was injected intraperitoneally immediately prior to the onset of recording. In the acute experiment, the effect of MGO was compared to pre- and post-drug control days. In the chronic experiment, a sequence of 5 control days, 10 days of MGO treatment, and a further 8 control days was tested. Both acute and chronic administration of MGO resulted in increased paradoxical sleep (PS) latency and a small, but significant, decrease in PS during the first 4 h after injection. This effect seems to be specific to PS, as no effects of MGO on waking or total sleep were found. With chronic administration, no PS rebound occurred within the 8-h recording time during the 8-day post-treatment control period. How the RNA precursor can decrease PS and whether this effect may play a role in the memory-improving action of the substance is discussed in terms of an interrelationship between macromolecular synthesis, sleep, and memory, respectively.

Animals↗

Anisomycin blocks the late phase of long-term potentiation in the dentate gyrus of freely moving rats.

Freely moving rats, chronically implanted with stimulation electrodes in the medial entorhinal cortex and recording electrodes in the dentate gyrus, received two 400 micrograms intraventricular injections of anisomycin during a tetanization procedure that induced a long-lasting potentiation (72 hours) of the monosynaptic field potential. Inhibition of protein synthesis during the tetanization procedure did not immediately influence the induction of long-term potentiation (LTP). However, 3-4 hours after the beginning of tetanization the potentiation effect decayed progressively and was abolished totally during the remaining 7 day observation period. In control experiments anisomycin did not affect the slope of field EPSP's and produced a reversible depression of the population spike amplitude. These data indicate a relatively specific effect of the protein synthesis inhibitor on mechanisms involved in a late phase of LTP stabilization.

Animals↗

Localization of entorhinal cortex neurons projecting to the dorsal hippocampal formation--a stereotaxic tool in three dimensions.

After topical injection of horseradish peroxidase into the dorsal hippocampal formation, the distribution of retrogradely labelled neurons of the entorhinal cortex was investigated. The distribution of these cells, which are projecting to the dorsal hippocampal formation, is demonstrated by drawings representing series of frontal, sagittal and horizontal sections and including stereotaxic coordinates. These drawings can be used as a morphological and stereotaxic tool in neurobiological research. Controversial opinions as to the dividing of the entorhinal cortex into subfields are discussed.

Afferent Pathways↗

Identification of neurons of origin providing the dopaminergic innervation of the hippocampus.

It was proved if there is an innervation of the hippocampus by dopaminergic neurons of the ventral tegmental area. Methods of labeling neurons by intrahippocampal injections of retrograde tracers were combined with fluorescence histochemical investigations of the same cells. An innervation of the hippocampus by the dopaminergic cell groups "A-9" and "A-10" could not be verified whereas, in the sphere of the raphe nuclei besides serotoninergic cells retrogradely labeled neurons were found exhibiting a dopamine like aminergic fluorescence.

Animals↗

Aminergic blockade modulates long-term potentiation in the dentate gyrus of freely moving rats.

Long-term potentiation (LTP) was induced in the dentate gyrus of freely moving rats by tetanic stimulation of the medial entorhinal cortex under conditions of catecholamine depletion by 200 mg/kg alpha-Methyl-para-tyrosine (AMPT) or blockade of alleged dopamine receptors by 0.5 mg/kg haloperidol. Both substances did not change significantly the normal excitability of the glutamatergic perforant pathway, but affected the establishment of LTP. Whereas the potentiation effect on the EPSP component of the monosynaptic field potential was not changed by both substances when compared to the potentiation of controls, the potentiation of the population spike was prolonged and enhanced. These results point to an effect of catecholaminergic blockade on postsynaptic membranes of the target cells or on other components of the neuronal network but not to a specific influence on the homosynaptic mechanisms of LTP.

Animals↗

[Evidence for transmitter-specific modulation of slow, rhythmic activity of the hippocampus].

In freely moving male Wistar rats the hippocampal EEG was recorded by using chronically implanted "chemitrodes" (combination of guide cannula and bipolar recording electrodes). A part of the animals received additionally stimulating electrodes in the dorsomedial hypothalamus. In order to characterize specific effects of presumable transmitter substances the hippocampal rhythmic slow activity (RSA) was divided into two types: (1.) slow RSA (5.0 to 7.5 Hz) which occurred spontaneously during orienting behaviour of the animals and (2.) fast RSA (7.5-12.0 Hz) which could be evoked by 100-Hz-stimulation of the hypothalamus. The intrahippocampal depletion of norepinephrine, dopamine, and serotonin did not influence both types of RSA. The alpha-adrenergic antagonist phenoxybenzamine depressed the generation of RSA in a frequency range of 7-8 Hz. The muscarinic agonist oxotremorine caused a long-lasting increase of slow RSA. The latter effect was blocked by the muscarinic antagonist scopolamine. In the same way another muscarinolytic drug (QNB) depressed the spontaneous slow RSA. The intrahippocampal activation of nicotinic receptors inhibited RSA generation, whereas the systemic application of nicotine increased the RSA for a short time. Clonidine which is known to be a noradrenergic agonist at presynaptic alpha-receptors induced a long-lasting slow RSA following intrahippocampal injection. This effect can be discussed as a presynaptic regulation of transmitter release in cholinergic terminals. The results described here support the conclusion that the slow RSA is a sign of a activation of hippocampal muscarinic receptors whereas others of the examined non-cholinergic transmission systems are not involved directly in the RSA generation.

Animals↗

Dopaminergic innervation of the hippocampus: evidence for midbrain raphe neurons as the site of origin.

The purpose of the study was to verify the site of origin of a postulated dopaminergic (DA) innervation of the hippocampus (HPC) in rats. The retrograde labeling of hippocampal afferents by Granular Blue (GB) was combined with the fluorescence histochemical identification of biogenic amines. Among the dopaminergic cell groups A8--A14 there was no one neuron labeled with GB. Some of the retrograde labeled neurons of the midbrain raphe nuclei (mainly B8-region) were identified as catecholaminergic, probably dopaminergic. It is concluded that mesencephalic dopaminergic fibers innervate the HPC, but that they arise from raphe nuclei rather than from the ventral tegmental area. In order to confirm these data neurophysiologically, hippocampal responses to electrical stimulation of midbrain raphe nuclei were recorded in freely moving Wistar rats. The intrahippocampal injection of the DA antagonist haloperidol through a chronic microcannula caused two types of changes in average evoked potentials: A significant decrease in the amplitude of an early, negative component (peak latency 8 ms). An increase in the amplitude of a second, positive component, which occurred only after a preceding inhibition of serotonine synthesis. The haloperidol sensitivity of the early component of hippocampal responses is interpreted as support of the morphological data about an ascending dopaminergic input from the median raphe nucleus to the hippocampus.

Afferent Pathways↗

Footshock-induced modification of a monosynaptic evoked potential in the hippocampus.

Parameters of dentate gyrus field potentials evoked by stimulation of the perforant path were studied in freely moving rats before and after repeated footshock application. An increase of population-EPSP steepness and a shortening of population spike latency was demonstrated immediately after the footshocks. These results indicate control for variables in behavior should be included in studies of monosynaptic potentials.

Animals↗

Is a retrosplenial (cingulate) pathway involved in the mediation of high frequency hippocampal rhythmical slow activity (theta)?

In previous experiments we demonstrated that in rats there are two kinds of hippocampal rhythmical slow activity patterns (RSA or theta) as defined by the dominating EEG frequencies. RSA with a frequency of 6-8 Hz appeared during exploratory behavior (locomotion), whereas stimulation of the dorsomedial hypothalamus (DMH) elicited RSA with frequencies of 8-12 Hz. To determine the neural pathways involved in the mediation of these two types of RSA, local injections of tetracaine were made either in the medial septum or in the cingulate cortex in order to reversibly interrupt the functional activity of these loci. Blockade of the medial septum suppressed the 6-8 Hz 'walking-associated' RSA in the hippocampal EEG, but had no effect on the 8-12 Hz DMH-driven RSA. On the other hand, a tetracaine injection into the cingulate cortex selectively blocked the high-frequency RSA elicited by DMH stimulation, but had no effect on the 6-8 Hz 'walking-associated' RSA. Both effects disappeared between 30 and 90 min after tetracaine injection. We conclude that the DMH-driven RSA is mediated by the cingulum and/or fibers traveling through the cingulate cortex (retrosplenial region) and thus, that this type of RSA operates without septal involvement.

Animals↗

Evidence for dopamine as a transmitter in dorsal hippocampus.

Intrahippocampal distribution of dopamine (DA) and its metabolites, homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), was studied along with those of noradrenaline (NA) and 5-hydroxytryptamine in rats. DA concentration in the dorsal part of the hippocampus was found to be 4--10 times higher than in other parts. A study of metabolite distributions produced similar results, showing a higher concentration in the dorsal part of the hippocampus. A ratio of NA/DA had a value similar to that of the hypothalamus in which apparent dopaminergic innervation has been reported. Haloperidol decreased the DA level, whereas it increased the concentration of metabolites, in whole and dorsal hippocampus. The ratio HVA/DOPAC increased after haloperidol treatment. These findings strongly suggest the presence of dopaminergic innervation in at least the dorsal part of the hippocampus.

3,4-Dihydroxyphenylacetic Acid↗

Rhythmical slow wave electroencephalographic activity elicited by hippocampal injection of muscarinic agents in the rat.

In freely moving male Wistar rats the hippocampal EEG was recorded by using chemitrodes (combinations of guide cannulas with bipolar recording electrodes) chronically implanted into the dorsal hippocampus (CAI). The muscarinic agents oxotremorine and arecoline applied intrahippocampally caused a long-lasting increase in the amount of rhythmical slow wave activity (RSA) of the hippocampal EEG accompanied by a decrease of the dominating frequency. At the same time, the well-known relationship between defined behavioral states and EEG patterns was abolished. The effect of oxotremorine could be blocked by subsequent application of the muscarinic antagonist scopolamine. The results support the hypothesis that a non-rhythmic activation of hippocampal muscarinic receptors may result in the generation of RSA within the hippocampal formation.

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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.

Animals↗