An inhibitor of integrin receptors blocks long-term potentiation.
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Animals↗
Biomedical subjects
U Staubli
Publications and source records attributed to U Staubli.
Induction of ornithine decarboxylase by subseizure stimulation in the hippocampus in vivo.
Electrical stimulation of the Schaffer-collateral axonal system under conditions which do not elicit detectable seizure activity causes an increase in the activity of ornithine decarboxylase (ODC), the rate limiting enzyme of polyamine synthesis, in the hippocampus, olfactory cortex, neocortex and olfactory bulb. The degree of ODC activation is dependent upon the stimulus parameters. The results support the hypothesis that neuronal activity regulates hippocampal polyamine concentrations.
Animals↗
Antagonism of NMDA receptors impairs acquisition but not retention of olfactory memory.
Prompted by evidence pointing to a key role of the N-methyl-D-aspartate (NMDA) receptor system in the induction of long-term potentiation and possibly in the formation of some types of memory, we examined the effect of chronic intraventricular administration of D-amino-phosphono-valeric acid (AP5), a competitive NMDA receptor antagonist, on olfactory discrimination and avoidance learning. These two tasks were selected because they are affected to very different degrees by damage to the hippocampus and other telencephalic structures rich in NMDA receptors. Twenty rats previously trained to solve a series of discriminations between two simultaneously presented odors were infused with either 20 mM D-AP5 or saline (n = 10 per group) for 14 days. An important and unusual feature of the paradigm was that it permitted a comparison of drug effects on acquisition of new discriminations versus retention of old ones. Animals treated with AP5 made significantly more errors than did saline controls in acquiring discriminations between low-intensity odors presented with long intertrial intervals (ITIs). However, no deficit was observed when short ITIs (less than 2 min) or strong odors were used. Animals treated with AP5 had no difficulty in recognizing odors on which they were trained before administration of the drug. After exhaustion of the pumps, performance of the AP5 group was indistinguishable from that of the control group. One-way active avoidance learning was not affected by chronic infusion of AP5. Several possibilities are discussed that could account for the selective olfactory learning deficit.(ABSTRACT TRUNCATED AT 250 WORDS)
2-Amino-5-phosphonovalerate↗
Chronic administration of a thiol-proteinase inhibitor blocks long-term potentiation of synaptic responses.
It has been proposed that activation of a calcium-sensitive protease (calpain) is a crucial step in the induction of long-term potentiation (LTP). To test this hypothesis, we used chronic recording techniques to measure the effects of intraventricular infusion of leupeptin, a calpain inhibitor, on LTP in the hippocampus. Rats implanted bilaterally with stimulating electrodes in the Schaffer-commissural system and one recording electrode in the apical dendrites of field CA1 were fitted with osmotic mini-pumps delivering either leupeptin (20 mg/ml) or saline at a rate of 0.5 microliter/h into the lateral ventricle. Short bursts of high-frequency stimulation with the bursts delivered at 5/s were used to induce LTP in those animals which had stable responses for several days. Rats in the saline group (n = 11) exhibited an immediate LTP effect that remained in place over successive days of testing, while only 3 of 13 leupeptin treated animals showed evidence of LTP 24 h after high-frequency stimulation, and in only one of those was a sizeable effect recorded over several days. The average change in responses at the 24-h test point was +33% for the controls and +4% for the leupeptin group (P less than 0.01). The block of LTP induction was reversible, since high-frequency stimulation applied after disconnecting the pumps led to a robust LTP effect that lasted for several days in 6 of 7 animals tested. There were no detectable differences in baseline responses in the presence and absence of leupeptin.
Animals↗
Stable hippocampal long-term potentiation elicited by 'theta' pattern stimulation.
The stability of long-term potentiation (LTP) elicited by a stimulation paradigm in which short high-frequency bursts of pulses were given in a 'theta' pattern (i.e. 5 bursts/s) was tested in a chronic recording study. Stimulation electrodes were implanted bilaterally in the Schaffer-commissural system while the recording electrode was placed in the apical dendritic field of the Ca1 zone of the hippocampus. Following 4 days of baseline testing, 'theta' stimulation was applied to one electrode for a total of 2 s (ten 30 ms bursts), after which testing was continued for 3 weeks or until the responses fell to below baseline levels. Data were collected from 25 animals and 3 types of results were obtained: (1) no LTP (n = 4), (2) LTP that decreased steadily from 24 h after high frequency stimulation onward (n = 4), and (3) LTP that was stable until recording was terminated or until the responses began a precipitous decrease to below baseline values (n = 17). The mean of the slopes of the curves relating degree of potentiation to days after 'theta' stimulation was less than 1%/day with a mean correlation coefficient of only 0.1 prior to the point at which the responses began their rapid decline. Control responses were unaffected by the induction of LTP in neighboring CA1 afferents and did not exhibit a reliable relationship with time. These results suggest that, for most rats, LTP elicited by theta pattern stimulation is stable until such time that stimulation-recording arrangements begin to deteriorate.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Evidence for synaptic potentiation in a cortical network during learning.
The connections between the lateral olfactory tract (LOT) and layer I of the piriform cortex were used to test the idea that certain forms of learning involve potentiation of cortical synapses. Rats were trained on a series of two-odor discriminations over a period of several days after which patterned electrical stimulation (short, high frequency bursts with 5-6 bursts per second) of the LOT was used as a discriminative cue. The animals reacted to the stimulation as though it were an odor and quickly learned to respond appropriately and to distinguish between 'positive' and 'negative' electrodes. Comparisons of the monosynaptic responses in the piriform cortex evoked by single pulse stimulation of the LOT before and after learning revealed that the population synaptic responses were substantially potentiated by the training. This effect was present in an unchanged form 24 h later. Responses elicited by control stimulating electrodes were slightly or not at all affected by training to stimulation with another electrode. Synaptic potentiation was not found in a small group of rats that did not learn to respond to patterned stimulation and was also absent when the stimulation was applied to naive rats. These results provide evidence that rapid learning of a specific cue potentiates cortical synapses in a defined terminal field.
Animals↗
Role of dorsomedial thalamic nucleus and piriform cortex in processing olfactory information.
Four experiments were conducted to characterize the role of primary and secondary olfactory projection areas (piriform cortex and dorsomedial thalamic nucleus (DMN] in olfactory information processing. Rats had to learn to discriminate between odors that were simultaneously released from different arms of an automated olfactory maze. When standard training conditions were used, damage of the DMN severely impaired both preoperatively trained and naive animals in acquiring an odor discrimination set (i.e. in most problems no learning was demonstrated). An additional group of DMN animals that received 4 times the standard amount of daily trials was unable to acquire the first two problems but successfully solved the third and all subsequent discriminations. Analysis of performance patterns suggested that destruction of the DMN initially leads to a strong procedural impairment that can be overcome by extensive training. After solving the third problem the animals with DMN damage required much less training to reach the learning criterion but generally made more errors than controls. Transfer of savings rarely occurred when a problem was repeated. Whether this secondary learning deficit observed in later discriminations is due to a specific effect of the lesion on the encoding of olfactory cues and thus on memory formation, or due to a disturbance in the regulation of emotional factors such as motivation, arousal, and attention is discussed. Lesions of the thalamus that spared the DMN had no effect on learning or retention of olfactory discriminations. Animals with ablations of the piriform cortex only acquired odor discriminations if they had been trained in the olfactory maze before the lesion. Moreover, their performance depended on the odor quality: they had great difficulty learning complex cues consisting of several odorants and learned simple odors virtually identical to control rats. The results indicate that an intact piriform cortex is needed to acquire the procedures involved to perform an olfactory discrimination task as well as to build neural representations of olfactory cues.
Animals↗
Olfaction and the "data" memory system in rats.
A set of studies was conducted to characterize the memory system involved in successive olfactory discrimination learning in rats. Two odors emanated from different arms of a radial maze; one of the arms contained a water reward. After training on four or five pairs of odors (20 trials per day), rats learned to discriminate the members of a new pair in 5-10 trials. Experiments in which either member of the pair was compared with a novel cue indicated that the rats learn both positive and negative odors, rather than simply ignoring the negative cue. The memories for the odors were apparently persistent, and no evidence for retroactive interference from subsequent training was obtained. Training on 30 pairs did not result in any slowing of subsequent learning, which suggest that the capacity of the memory system for odors is substantial. In a second group of experiments, we tested whether rats distinguish between odors by identifying unshared subcomponents or instead treat odors in a gestalt (i.e., unitary) fashion. Animals trained on three component odors with two in common did not recognize the elements that were unshared when these were presented by themselves. Even when one of the two shared components was combined with the differentiating component into a cue (i.e., two thirds of the original three-component odor), the new cue was treated as a novel odor. However, inclusion of a previously learned simple odor in a complex odor did affect the learning of that odor.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Studies on retrograde and anterograde amnesia of olfactory memory after denervation of the hippocampus by entorhinal cortex lesions.
The effect of hippocampal denervation on olfactory memory in rats was tested after interrupting the lateral olfactory tract projections at the level of the entorhinal cortex. When lesioned animals were trained to learn new odors, they showed no evidence of retention 3 h after acquisition. These results confirm earlier data on rapid forgetting in rats after hippocampal deafferentation and are in parallel to the anterograde amnesia typically found in humans with hippocampal damage. On the other hand, preoperatively learned information was minimally impaired after hippocampal deafferentation even if it was acquired within less than 1 h before the lesion. This finding differs from reports on humans as well as monkeys with hippocampal damage where memories formed during a critical time span of months or even years before the lesion are found to be impaired. This may suggest that the consolidation process in humans and rodents has different time scales or that the roles of the human and the rat hippocampal structure in memory formation are somewhat different.
Amnesia↗
Up-hill avoidance: a new passive-avoidance task.
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Animals↗
Differential effects on learning by ventromedial vs lateral hypothalamic posttrial injection of substance P.
The effects of post-trial injection of substance P (SP) into the lateral hypothalamus (LH) and the ventromedial hypothalamus (VMH) on passive avoidance learning was studied in rats. In the VMH, 50 ng and 500 ng SP influenced neither learning of a step-down avoidance nor of an alcove avoidance response. In contrast to these findings, 500 ng SP injected into the LH significantly enhanced retention of the alcove avoidance task. Similarly, in the step-down avoidance experiment, learning was strongly facilitated by posttrial injection of 50 ng as well as 500 ng SP into the LH. These results, together with our previous data showing amnesia with posttrial injection of SP into amygdala and substantia nigra, suggest that exogenously applied SP influences the activity of those brain regions shown to contain high densities of SP-positive nerve terminals. Interestingly, the effects of posttrial SP injection parallel the effects of post-trial electrical brain stimulation on passive avoidance learning. Hence, posttrial SP retroactively facilitates or impairs learning depending on where in the brain it is injected.
Animals↗
Post-trial injection of substance P into lateral hypothalamus and amygdala, respectively, facilitates and impairs learning.
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Amygdala↗
Retrograde amnesia produced by post-trial injection of substance P into substantia nigra.
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Amnesia↗
Effects of post-trial reinforcing vs. subreinforcing stimulation of the substantia nigra on passive avoidance learning.
Experiments were designed to investigate the role of post-trial reinforcing and subreinforcing stimulation of the substantia nigra on memory processing. Thirty sec post-trial reinforcing stimulation (0.2 sec on/1.8 sec off) impaired learning of response suppression in a step-down task compared to control animals as well as to animals stimulated at subthreshold current level (i.e., at 25% of the current level shown to maintain optimal self-stimulation in previously performed self-stimulation sessions). In a second small-box passive avoidance experiment, i.e., the alcove-avoidance task, opposite results were attained: Subreinforcing stimulation attenuated learning whereas neither suprathreshold stimulated animals nor control animals showed impairment of learning. The conclusions drawn from these results are as follows: Post-trial stimulation of the substantia nigra interferes with memory processing. This attenuation of learning is obviously task-dependent and can additionally be influenced by the quality of the stimulation, i.e., whether it is reinforcing or not. Possible explanations to account for these task-dependent and quality of stimulation-dependent effects of post-trial substantia nigra stimulation are discussed.
Animals↗
Proactive and retrograde effects on LTP produced by theta pulse stimulation: mechanisms and characteristics of LTP reversal in vitro.
Previous studies have established that (1) a 1-min episode of theta pulse stimulation (TPS) is sufficient to reverse potentiation during the early phases of LTP in area CA1 without causing depression when administered to nonpotentiated pathways; (2) the magnitude of depotentiation is inversely related to the delay between LTP induction and reversal attempts; and (3) pharmacological facilitation of AMPA receptor-mediated currents significantly enhances the strength of the reversal mechanism. The present experiments confirm and extend these results by showing that the depotentiating action of TPS on prior LTP is antagonized by inhibitors of protein phosphatases and adenosine A1 receptors but is not affected by NMDA receptor blockade, and, moreover, that TPS interferes with subsequent LTP induction by triggering an inhibitory mechanism that is active for a few minutes and is blocked by phosphatase inhibition. The possible implications of these results are discussed.
2-Amino-5-phosphonovalerate↗