From molecular mechanisms to behavior.
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Animals↗
Biomedical subjects
H Matthies
Publications and source records attributed to H Matthies.
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.
Animals↗
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.
Animals↗
Increase of paradoxical sleep (PS) by intraperitoneal injection of brain extract from PS-deprived rats.
Intraperitoneal injection of a brain extract obtained from paradoxical sleep-(PS) deprived donor rats resulted in a small but significant increase of PS in normal recipient rats. Brain extract of non-deprived control rats was without effect. The results provide further evidence for the existence of a PS-inducing factor accumulating in the brain during PS deprivation.
Animals↗
Metabolism of beta-casomorphin and its derivatives in rat brain and liver homogenates.
Derivatives of opiate-like acting beta-casomorphin (beta-CM), (Tyr-Pro-Phe-Pro-Gly), were prepared by substitution of D-amino acids. The metabolism of these analogs was studied in brain and liver homogenates. Their half-lives and the metabolites resulting from their biological degradation were determined by means of the HPLC-technique. Resistance to biological degradation, which was considerably enhanced in some derivatives, was shown to depend on the position of the D-amino acids. The following substances proved to be particularly stable: D-Pro2-beta-CM, Des-Tyr-D-Pro2-beta-CM, Des-Tyr-D-Phe3-beta-CM. The resulting metabolites suggest that the activity of proline-specific peptidases is predominant in the catabolic process. The degradation pattern of beta-CM-pentapeptides produced by peptidases in the brain and liver is completely different from that of the enkephalin-pentapeptides, which are likewise protected by substitution of D-stereoisomers for certain L-amino acids. The different degradation kinetics of beta-CM-pentapeptides in neuronal and non-neuronal tissue homogenates (liver) reflect the variation in activity of certain peptidases. Considering the half-lives that we have estimated, we suggest which of the peptides tested has a high resistance against biological degradation in vivo.
Amino Acid Sequence↗
The effect of beta-casomorphins on the apomorphine- and amphetamine-induced turning after nigral lesions in rats.
To characterize the action of derivatives of beta-casomorphin their influence on the apomorphine- or amphetamine-induced turning behaviour following unilateral lesion of the substantia nigra with 6-hydroxydopamine was investigated. The beta-casomorphins studied, (D-Pro4-beta-casomorphin1-5, D-Phe3-beta-casomorphin1-5, Des-Tyr1-D-Pro4-beta-casomorphin2-5 or Des-Tyr1-D-Phe3-beta-casomorphin2-5), did not change postsynaptic dopaminergic processes in the striatum of the rat after intraperitoneal injection of apomorphine. On the contrary, the turning induced by amphetamine was modified by beta-casomorphins. Increased amphetamine-evoked turning could be observed after intrastriatal application of tyrosine-containing beta-casomorphins (D-Pro4-beta-casomorphin1-5 or D-Phe3-beta-casomorphin1-5), whereas presynaptic dopaminergic mechanisms were inhibited by injection of the corresponding des-tyrosine beta-casomorphin analogs (Des-Tyr1-D-Pro4-beta-casomorphin2-5 or Des-Tyr1-D-Phe3-beta-casomorphin2-5) into the striatum after administration of amphetamine.
Amphetamine↗
Low frequency perforant path stimulation as a conditioned stimulus demonstrates correlations between long-term synaptic potentiation and learning.
Stimulation of the perforant path with impulse trains of 15 cps and 670 msec duration was used as a conditioned stimulus in a two-way shuttle box avoidance on rats. Field potentials in the dentate area evoked by test stimuli were measured after the training sessions until the 7th day. Foot-shock and unconditioned escape elicited only a transient slight depression of the population spike amplitude (P) and increased also slightly the slope function (SF) of the population EPSP of the evoked test potentials. The control stimulation of the perforant path without pairing with foot-shock as in conditioning did only slightly increase SF of test potentials, but produced a strong transient inhibition followed by a long lasting moderate depression of P. After conditioning, all animals exhibited the same initial inhibition of P as shown in control stimulation of the perforant path. However during the following 4 hours, good learners with a relearning index greater than 30% developed a significant potentiation of P lasting until the second training session 24 hours later, which resulted in a further enhancement. SF of the evoked test potentials increased in good learners with a similar time course after conditioning but without initial depression. After 7 days P showed still enhanced but non-significant values. Poor learners with a relearning index less than 10% did not develop a potentiation of P after conditioning and initial inhibition, but a long-term depression. Also SF of test potentials decreased in poor learners during 4 hours after conditioning and returned almost to baseline until the following day. After 7 days, P and SF did not differ from baseline. The analysis of the observed synaptic changes by E-S curves demonstrated the post-tetanic LTP seems to differ in some ways from post-conditioning LTP in good learners. The latter exhibits a clear tendency of a right shift contrary to the left shift commonly occurring after tetanization. Furthermore poor learners do not only fail to produce long-term potentiation, but fail to show a change in the opposite direction with a left shift of the E-S curves. The observed correlation of LTP in the conditioning pathway with the learning ability suggests an involvement of LTP at least in the acquisition and early retention of this learned behavior. The results do however not finally clarify the role of LTP in long-term retention.
Animals↗
Impairment of glycoprotein fucosylation in rat hippocampus and the consequences on memory formation.
The intraventricular injection of 2-deoxy-D-galactose led to a dose- and time-dependent decrease in the fucosylation of hippocampal glycoproteins in rats whereas the incorporation of 3H-N-acetyl-glucosamine was not influenced. This effect is not related to an interference with fucose activating or transferring enzymes but can be abolished by an application of D-galactose. Thus, it seems likely that also in brain tissue a deoxy-galactose induced decrease in the fucosylation is due to a hindering of a glycosidic linkage of fucose to the deoxy-sugar incorporated into glycoprotein chains. As a consequence of an intrahippocampal injection of the deoxy-sugar the retention performance of the animals in a foot-shock motivated brightness discrimination task was considerably impaired. But deoxy-galactose is effective only when administered before and immediately after training whereas either a pre- or a post-training injection did not influence the retention performance of the rats. Thus, an effective metabolic inhibition of the glycoprotein completion by the deoxy-sugar starting at the time of training seems to be crucial to interfere with such morphofunctional alterations in the neuronal network underlying the formation of a memory trace.
Animals↗
Opioid-receptor blockade reduces nose-poke self-stimulation derived from medial entorhinal cortex.
Rats were trained to nose-poke for intracranial self-stimulation (SS) with electrodes unilaterally implanted in the medial entorhinal cortex. The acute effects of naloxone (NX; 0.1-10 mg/kg, IP) on a continuous reinforcement schedule were determined. Reductions in the self-stimulation rates occurred only at moderate doses (median of individual changes = -36% at 1 and 5 mg/kg), whereas the high dose (10 mg/kg) was ineffective. None of the doses influenced operant behavior. These results are consistent with the hypothesis that endogenous opioid-opiate receptor mechanisms play a modulatory role in SS reward. Considering that NX was administered systemically the action of the drug on reinforcement levels may be mediated by a site distinct from the locus of stimulation.
Animals↗
Calcium-induced long-term potentiation in the hippocampal slice: characterization of the time course and conditions.
A transient increase in extracellular calcium concentration causes a long-lasting enhancement of radiatum fibers evoked excitatory postsynaptic potential and population spike responses of CA1 pyramidal neurons which resembles long-term potentiation (LTP). The duration of this potentiation is much longer than described previously and is probably limited by the survival of the preparation itself (greater than 8 hr). Therefore, Ca-induced LTP can be used for the investigation of a postulated late phase of LTP. Ca effects were activity-independent, since the subsequently evoked responses were facilitated even when the presynaptic fibers were not concurrently stimulated during or immediately after superfusion with the high Ca medium. In contrast, if too frequent testing of the synaptic input was done during the high Ca pulse, a short lasting depression instead of potentiation was observed. A lower extracellular magnesium concentration in the standard medium (1.3 instead of 2.0 mM MgSO4) prevents the potentiation of the EPSP at least for the first few hours. Presumably, both tetanus- and Ca-induced LTP share some common mechanisms, since an additional tetanization after Ca induction was not followed by an additional LTP. Compared to the potentiation following tetanization, the Ca-induced LTP was, however, not accompanied by a potentiation of the EPSP/spike ratio within the range of the population spike threshold intensity.
Animals↗
[Principles of neuronal information storage. Theories, methodology, experiments].
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Animals↗
Degradation of beta-casomorphin in the rat brain in vivo.
The degradation of beta-casomorphin 1-5 (Tyr-Pro-Phe-Pro-Gly (beta CM]--an opiate-like acting pentapeptide--was investigated in brain stem and corpus striatum of male Wistar rats during the first 20 min after an intracerebroventricular (i.c.v.) application of 166 nmol [3H]Phe3-beta CM. Dependent on the time after [3H]Phe3-beta CM injection, the radioactivity carried by beta CM and its metabolites was estimated in the HCl-soluble tissue fraction of these brain structures. The separation of the intact pentapeptide from its metabolites was performed using HPLC-technique. In both brain regions a rapid decrease in the concentration of beta CM was observed during the first 10 min after [3H]Phe3-beta CM application (1st phase). 10 to 20 min after injection, the decrease in beta CM concentration was found to be considerably smaller (2nd phase). Moreover, beta CM is rapidly degraded forming phenylalanine and tyrosine as the main metabolites. Furthermore, at any time, small amounts of Phe-Pro-Gly, Phe-Pro, Pro-Phe-Pro-Gly and Tyr-Pro-Phe-Pro were estimated. From these results, the analgesic effect by i.c.v. application of 166 nmol beta CM is assumed to be caused rather by the intact pentapeptide molecule than by one of its metabolites.
Animals↗
[Patient goals and therapist behavior patterns in triadic partnership therapy].
From various concepts of therapy an integrative attempt at a three-way partnership therapy (two partners and a therapeutist) has developed, with observable and testable interaction variables (concretised as patients' aims and therapeutists' behavior) being derived. Patients' aims (aims to advance the therapy) are regarded as one aspect of the relationship, which it is attempted to improve. Besides considering the verbal behavior of patients and therapeutist, patients' experience during treatment and experience outside of the therapy were examined. Empirical investigation has show that the integration of therapeutists' variables can frequently achieve certain targets in patients' behavior, and that a partial breakup of destructive communication patterns and alterations on the level of experience attitudes, ........, emotions, etc.) can be achieved.
Adaptation, Psychological↗
Effects of intrastriatal microinjection of beta-casomorphins and its Des-tyrosine derivatives on rat motor behaviour.
After unilateral striatal application the tyrosine-containing and Des-tyrosine analogues of beta-casomorphin were investigated with regard to the properties inducing rotational behaviour in rats. The tyrosine-containing beta-casomorphins (D-Pro4)-beta-casomorphin1-5, (D-Phe3)-beta-casomorphin1-5 or (D-Pip4)-beta-casomorphin1-5 produced contralateral rotations like apomorphine, whereas the Des-tyrosine-beta-casomorphins brought about an ipsilateral haloperidol-like asymmetry; (Des-Tyr1-D-Pip4)-beta-casomorphin2-5 did not evoke a lateralization of motor behaviour. The contralateral turning following unilateral apomorphine application into striatum was increased by striatal administration of tyrosine-containing beta-casomorphin analogues and antagonistically influenced by (Des-Tyr1-D-Pro4)-beta-casomorphin2-5 or (Des-Tyr1-D-Phe3)-beta-casomorphin2-5; however, (Des-Tyr1-D-Pip4)-beta-casomorphin2-5 has no effect on apomorphine-induced rotation behaviour. The time course of the animals' asymmetric motor behaviour after striatal apomorphine administration was antagonistically influenced by haloperidol, (Des-Tyr1-D-Phe3)-beta-casomorphin2-5 or (Des-Tyr1-D-Pro4)-beta-casomorphin2-5; quantitative differences were observed as far as the strength and the duration of the apomorphine antagonistic effect of Des-Tyr-beta-casomorphins are concerned.
Animals↗
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↗
Influence of postnatal hypoxia on learning and memory formation of adult rats.
Male Wistar rats were exposed to a single normobaric hypoxic treatment at the age of either 15 or 20 days. Two different kinds of hypoxia were used: 4% O2 for 6 h or 3.5% O2 for 40 min. At the age of 8 weeks the acquisition and retention of a brightness discrimination was investigated in all animals. The acquisition of all treated animals did not differ from the corresponding controls. Both hypoxic treatments at the 20th day resulted in a significant improvement of retention in the adult age, whereas only hypoxia with 3.5% O2 for 40 min at the 15th day showed a similar effect, the treatment with 4% O2 for 6 h at this time was ineffective.
Age Factors↗
Effects of carbohydrate precursors of glycoproteins on retention performance of a brightness discrimination task in rats.
The influence of intraventricularly applied carbohydrate precursors of glycoproteins on acquisition and retention of a brightness discrimination task in rats was tested. The injection of 0.8 mumoles L-fucose/animal, N-acetylneuraminic acid or D-galactosamine as well as 2.4 mumoles/animal D-galactose or D-glucosamine 30 min before starting the behavioural experiments significantly improved the retention performance of the acquired behaviour. The intraventricular application of 2.4 mumoles D-mannose/animal had no influence on the behavioural parameters tested. The results are discussed in the light of an activation of glycoprotein formation in brain tissue mainly by carbohydrates which occupy terminal positions in the oligosaccharide chains.
Animals↗