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U Stäubli

Publications and source records attributed to U Stäubli.

16 recordsLinked to original sources
PubMed1999

Time-dependent reversal of long-term potentiation in area CA1 of the freely moving rat induced by theta pulse stimulation.

Previous studies in slices have shown that low-frequency stimulation at 5 Hz, i.e., theta pulse stimulation (TPS), completely reverses long-term potentiation (LTP) in area CA1 when delivered within 1-2 min after induction but produces progressively less depotentiation at longer delays, until it has no longer any impact at 30 min after induction. The present study examined whether LTP in the freely moving rat exhibits a similar time-dependent susceptibility to reversal. Adult male Long-Evans rats with bilateral stimulating electrodes activating collateral/commissural projections to area CA1 were used. A 1 min episode of TPS, ineffective when applied to naive pathways, was found to permanently erase LTP when delivered to the test pathway either 30 sec or 15 min after induction. Administered at a delay of 30 min, however, the same treatment no longer had any impact on established LTP. Additional experiments examined the ability of shorter TPS episodes to erase LTP and found that a 30 sec treatment was effective at 30 sec but not 15 min after induction. When the duration of TPS was further reduced to 15 sec, a reversal was no longer obtained at any delay. These results provide the first demonstration that the limited vulnerability of LTP to reversal by TPS, originally observed in vitro, also holds true for LTP in the awake animal and occurs along the same time frame, supporting the notion that LTP stabilization mechanisms take less than 30 min to be complete.

Animals↗
PubMed1999

GABAB receptor antagonism: facilitatory effects on memory parallel those on LTP induced by TBS but not HFS.

The present experiments used CGP 35348, a selective GABAB receptor antagonist with a significantly higher affinity for post- versus presynaptic receptors, to dissociate the role of antagonist concentration versus stimulation mode in determining whether GABAB receptor blockade facilitates or suppresses long-term potentiation (LTP). The antagonist was applied by pressure ejection to one of two recording sites in area CA1 of hippocampal slices before LTP was induced at both sites with either theta burst or high-frequency stimulation (TBS or HFS). TBS produced a dose-dependent facilitation of potentiation that turned into depression at the highest concentration tested, a result reflecting the dose-dependent balance between the drug's postsynaptic disinhibitory effect and its action on presynaptic autoreceptors regulating the release of GABA. In contrast, HFS-induced LTP increased monotonically with drug concentration, suggesting that blockade of postsynaptic GABAB receptors is the only factor contributing to HFS-induced LTP. To test the relevance of the two sets of LTP results, we performed behavioral studies examining the effect of different dosages of antagonist on spatial retention and found that memory was enhanced at intermediate dosages but not at very low and high concentrations, reminiscent of the bell-shaped dose-response curve obtained for TBS-induced LTP. These findings are consistent with the notion that LTP induced by electrical stimulation modeled after endogenous theta-modulated activity patterns bears more relevance to behavior than does potentiation induced by arbitrary tetanic trains.

Analysis of Variance↗
PubMed1998

Time-dependent reversal of long-term potentiation by an integrin antagonist.

The integrin antagonist Gly-Arg-Gly-Asp-Ser-Pro (GRGDSP) was applied by local ejection to one of two recording sites in hippocampal slices at various times before and after long-term potentiation (LTP) was induced at both sites with theta burst stimulation. Applications 10 min before, immediately after, and 10 min after induction caused LTP at the experimental site to decay steadily relative to that at the within-slice control site. However, application at 25 min or more after induction had no detectable effect on potentiation. Similar results were obtained when the integrin antagonist was perfused into the slice rather than applied locally. The time period after induction during which GRGDSP interfered with LTP consolidation corresponds to that during which LTP is susceptible to reversal by low-frequency afferent stimulation and newly formed memories are vulnerable to various disruptive treatments. Comparable experiments using a peptide that blocks an extracellular binding site of neural cell adhesion molecules (NCAMs) did not yield time-dependent reversal of LTP; i.e., an antagonist that interacts with the fourth immunoglobulin-like domain reduced LTP when applied before induction but not afterward. Moreover, LTP formation occurred normally in the presence of an antibody against the fibronectin repeat domain of NCAM. These results suggest that integrin activation and signaling occurring over several minutes after LTP induction are necessary for stabilizing synaptic potentiation and by inference may be required for the conversion of new memories into a not readily disrupted state.

Amino Acid Sequence↗
PubMed1996

Factors regulating the reversibility of long-term potentiation.

Theta burst stimulation (TBS) produces an extremely stable form of long-term potentiation (LTP). In contrast, a brief episode of single-pulse stimulation at theta frequency [theta pulse stimulation (TPS)] has been demonstrated to reverse LTP in area CA1 of slices and freely moving animals without causing depression when administered to nonpotentiated pathways. The present in vitro studies confirm these results and establish that the susceptibility of LTP to reversal and the degree of depotentiation are time-dependent. Specifically, a 1 min train of TPS delivered 30 sec after LTP induction produced an almost complete and lasting depotentiation but had increasingly less impact at longer delays and virtually no effect at 30 min. Increasing the duration of TPS did not cause more depotentiation. However, pharmacological facilitation of AMPA receptor-mediated currents significantly enhanced the strength of the reversal process and allowed TPS to produce robust depotentiation up to 30 min after LTP induction. The reversal effect was selective to potentiated synapses receiving TPS, was reversible, and was not blocked by NMDA receptor antagonism. Additional experiments indicated that AMPA receptor facilitation promotes depotentiation by enhancing an active process triggered by TPS that reverses expression without extending the time course of consolidation. These results suggest that the mechanisms responsible for LTP reversal are linked to the amplitude and/or duration of fast excitatory currents mediated by synaptic AMPA receptors and are effective up to the completion of LTP stabilization.

Animals↗
PubMed1996

Remembrance of odors past: enhancement by central facilitation of AMPA receptors.

Pharmacological facilitation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA)-type glutamate receptor has recently been demonstrated to enhance synaptic responses, promote long-term potentiation (LTP) induction in freely moving rats, and facilitate learning and retention of information. The present study verifies and extends the behavioral action of allosteric AMPA receptor modulation by showing that the benzoyl-piperidine compound BDP-12 promotes retention of olfactory and transient spatial memory in a dose-dependent fashion; is only effective when given before but not after training, consistent with the hypothesis that glutamatergic facilitation enhances information encoding by means of action on the machinery involved in LTP induction; and, following suboptimal training in a paradigm of enduring memory, prolongs the ability of rats to retain odors by extending the decay of weak memory traces.

Animals↗
PubMed1995

Variants of olfactory memory and their dependencies on the hippocampal formation.

Olfactory memory in control rats and in animals with entorhinal cortex lesions was tested in four paradigms: (1) a known correct odor was present in a group of familiar but nonrewarded odors, (2) six known correct odors were simultaneously present in a maze, (3) correct responses required the learning of associations between odors and objects, and (4) six odors, each associated with a choice between two objects, were presented simultaneously. Control rats had no difficulty with the first problem and avoided repeating selections in the second; this latter behavior resembles that reported for spatial mazes but, in the present experiments, was not dependent upon memory for the configuration of pertinent cues. Control animals varied considerably in their acquisition of odor-object associations with only a subgroup learning every set of pairings. These latter animals also performed well in the fourth task and, as indicated by post hoc analyses, developed complex strategies in dealing with the problem of serial odor-object pairs. Lesioned animals had no difficulty in selecting correct odors learned prior to surgery (problem one) but repeated their choices in problem two. This latter result suggests that hippocampus contributes to the transient memory of prior choices for odors as it does for prior choices in spatial mazes. Entorhinal rats were able to form odor-object associations (problem three), and a subgroup of the animals periodically succeeded in doing a long series of such choices (problem four), though with less frequency than controls. These results indicate that rats use both long-term memory and transient memory in dealing with olfactory problems and suggest that the second of these is dependent upon a hippocampal process that encodes a type of information other than the relationship between cues.

Animals↗
PubMed1995

Effects of 5-HT3 receptor antagonism on hippocampal theta rhythm, memory, and LTP induction in the freely moving rat.

Serotonergic brainstem projections to hippocampus are thought to preferentially target and increase, via 5-HT3 receptors, the excitability of a distinct subpopulation of interneurons that primarily regulate GABAB-mediated inhibition in the dendritic region of pyramidal cells. Hippocampal slice work suggests that the between-burst hyperpolarization caused by slow (GABAB) IPSPs plays a significant role in controlling the strength of LTP induced with theta burst stimulation. According to the above observations it was assumed that blockade of hippocampal 5-HT3 receptors should reduce the hyperpolarization and thereby enhance both the frequency of the naturally occurring theta rhythm and the induction of LTP; moreover, if LTP-like mechanisms provide the substrate for certain forms of memory, such treatment was expected to facilitate learning. Each of the above predictions was tested and confirmed in the present set of experiments. The effects of ondansetron, a potent and selective antagonist of the 5-HT3 receptor, were examined on (1) frequency of the hippocampal theta rhythm, (2) induction of LTP in field CA1 of freely moving rats, and (3) retention of olfactory and spatial memory in tasks known to depend on an intact hippocampus. When injected intraperitoneally into freely moving rats, the drug reliably and significantly increased the frequency of the hippocampal theta rhythm in a dose-dependent manner. Second, at concentrations that facilitate theta frequency (100 micrograms/kg and 500 micrograms/kg), an injection of the drug 30 min prior to delivering electrical stimulation bursts significantly increased the magnitude and duration of LTP compared to that obtained in the same animals after vehicle injections.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Centrally active modulators of glutamate receptors facilitate the induction of long-term potentiation in vivo.

An experimental drug, 1-(1,3-benzodioxol-5-ylcarbonyl)piperidine, that facilitates glutamatergic transmission in brain after systemic administration was tested for its effects on the induction of long-term potentiation in the hippocampus of rats. Intraperitoneal injections of the drug markedly increased the degree and duration of long-term potentiation; similar results were obtained with an analogue of 1-(1,3-benzodioxol-5-ylcarbonyl)piperidine that was also found to improve retention of memory in a radial maze task and in an odor-matching problem. These results define tools for enhancing long-term potentiation in vivo and confirm an important prediction from the hypothesis that long-term potentiation is a substrate of memory.

Animals↗
PubMed1985

Olfactory discrimination learning is blocked by leupeptin, a thiol protease inhibitor.

Rats were trained on successive two-odor discriminations with the cues randomly located in an 8-arm radial maze. After several days of training using different odor pairs, the thiol protease inhibitor leupeptin was infused into the ventricles and testing continued. Leupeptin caused a pronounced, dose-dependent and reversible deficit in performance in this task. Previous studies have shown that these drug concentrations do not influence spontaneous activity, feeding and drinking, or the acquisition and retention of avoidance conditioning. The results are interpreted as supporting the hypothesis that a calcium-sensitive proteinase is involved in certain forms of memory that require modification of telencephalic circuitries.

Animals↗
PubMed1985

Central action of substance P: possible role in reward.

A series of studies had revealed a dualistic role of post-trial injections of substance P in affecting avoidance behavior depending on the site of the brain in which it is applied. Based on these data, the hypothesis was formulated that substance P has brain site-dependent rewarding and punishing properties, a possibility which was assessed in rats trained on a modified T-maze task. Injections of substance P into the medial forebrain bundle (100 ng) or medial septal nucleus (500 ng) served as a positive reinforcer for conditioned place preference learning in the T maze. Injections into the amygdala (50 ng) or substantia nigra (100 ng) did not have such reinforcing properties.

Amygdala↗
PubMed1985

Pharmacological dissociation of memory: anisomycin, a protein synthesis inhibitor, and leupeptin, a protease inhibitor, block different learning tasks.

Inhibition of protein synthesis by anisomycin for a short duration impairs memory of a one-trial inhibitory avoidance task in rats. Memory of escape conditioning involving eight trials is disrupted only if the duration of protein synthesis is prolonged by repeated injections. In marked contrast, olfactory memory of rats trained on two odor discriminations is not affected by anisomycin even if the duration of inhibition is prolonged and the number of trials is reduced to a minimum. In previous work, leupeptin, a thiol proteinase inhibitor, was shown to impair olfactory discrimination learning, but left inhibitory and avoidance conditioning intact. Together, these results provide a pharmacological double dissociation of memory, and suggest that the same chemistries, or mixtures of chemistries, may not be involved in all types of memory.

Animals↗
PubMed1984

The distribution of the commissural-associational afferents of the dentate gyrus after perforant path lesions in one-day-old rats.

Lesions were made in the entorhinal cortex of one-day-old rats and the distribution of the axons in the dentate gyrus molecular layer studied with the Holmes silver stain when the animals reached adulthood. The commissural-associational projections, normally restricted to the inner dendritic zones, spread evenly throughout the molecular layer ipsilateral to the lesion. This pattern of aberrant growth is markedly different from that which occurs after entorhinal lesions placed in 7-day-old rats. The results are discussed in terms of the factors that dictate the topography of developing afferents.

Afferent Pathways↗
PubMed1984

Leupeptin, a thiol proteinase inhibitor, causes a selective impairment of spatial maze performance in rats.

The effects of chronic intraventricular infusion of leupeptin, a potent inhibitor of thiol proteinases, were tested on ingestive behaviors, escape and avoidance conditioning, and spatial memory in rats. The drug did not detectably influence feeding, drinking, body temperature, or the latency to escape from a mild footshock or inhibitory avoidance behavior. However, rats treated with leupeptin made numerous errors ( reentries ) in an eight-arm spatial maze. These results are interpreted as supporting the hypothesis that calcium-activated thiol proteinases are involved in the formation of certain types of memory.

Animals↗
PubMed1984

Hippocampal denervation causes rapid forgetting of olfactory information in rats.

Rats were trained on a succession of two-odor discriminations for a water reward in a modified radial maze. A different odor pair was used each day. After three or four pairs, rats would learn to choose the correct odor in only 3-5 trials. Animals were then subjected to electrolytic lesions in the lateral entorhinal cortex, which is innervated by the lateral olfactory tract, or in the dorsal entorhinal cortex, which is not a target of the olfactory system. Lesions of the first type did not interfere with performance, provided a short interval (30 sec to 2 min) was used between trials. However, the rats were severely impaired when trials were separated by 3-10 min. Dorsal lesions had no effect on olfactory discrimination irrespective of length of delay. In additional experiments, the rats were trained for 10 trials with short inter-trial intervals and then tested 1 hr later with the significance of the cues reversed. Animals with dorsal lesions continued to respond to the formerly correct odor while those with lateral entorhinal damage immediately reversed their response choices. These results provide evidence that lesions to the hippocampal system produce a rapid forgetting syndrome in rats comparable with that reported for humans with temporal lobe damage or dysfunction.

Animals↗
PubMed1980

Facilitation of learning by post-trial injection of substance P into the medial septal nucleus.

The undeca-neuropeptide substance P (SP) was injected post-trial into the medial nucleus of the septum to test its influence on passive avoidance learning in rats. A facilitation of learning was attained in the alcove avoidance task with doses of 50 ng (37 pmol), 500 ng (370 pmol) and 6.7 microgram (5 nmol) SP and in the step-up avoidance task with 500 ng and 6.7 microgram SP. In the step-down avoidance task no influence of SP was discernible, probably as a consequence of the high retention shown by control animals, masking a possible SP-induced facilitation of learning (ceiling effect). Interestingly, in its effect on learning, SP applied in the septum imitates the effect of electrical septal stimulation, thus providing another example for the parallelism between post-trial SP and electrical brain stimulation which we have demonstrated previously in the substantia nigra, amygdala and lateral hypothalamus.

Animals↗