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Y Dudai

Publications and source records attributed to Y Dudai.

At least 19 recordsLinked to original sources
PubMed2003

Skill learning in mirror reading: how repetition determines acquisition.

Practice makes perfect, but the role of repetitions in skill learning is not yet fully understood. For example, given a similar number of trials on a given task, it is debated whether repeating and non-repeating items are learned by the same neural process. When one is given training with both types of items--does one learn two separate skills, or only one? Here we show, using a mirror reading task, that practice trials with trial-unique words, and practice trials with repeated words, count towards learning to a different degree. There was no interaction between the time-course of learning repeated and unique words even within the same individuals given mixed training. While repeated words were learned faster than unique words, the repetitions-dependent gains diminished with training beyond a small number of repetitions. Moreover, the gains in performance could not be accounted for solely by the number of repetitions, as assumed by power-law models of learning; rather, the passage of time was a critical factor. Finally, our results suggest that although both repeated and new words were learned by both declarative and procedural memory mechanisms, even a single repetition of specific words could lead to the establishment of a selective differential representation in memory. The results are compatible with the notion of a repetition-sensitive process, triggered by specific repeating events. This 'repetition counter' may be a critical trigger for the effective formation of procedural as well as some type of declarative memory.

Adolescent↗
PubMed2001

Memory extinction, learning anew, and learning the new: dissociations in the molecular machinery of learning in cortex.

The rat insular cortex (IC) subserves the memory of conditioned taste aversion (CTA), in which a taste is associated with malaise. When the conditioned taste is unfamiliar, formation of long-term CTA memory depends on muscarinic and beta-adrenergic receptors, mitogen-activated protein kinase (MAPK), and protein synthesis. We show that extinction of CTA memory is also dependent on protein synthesis and beta-adrenergic receptors in the IC, but independent of muscarinic receptors and MAPK. This resembles the molecular signature of the formation of long-term memory of CTA to a familiar taste. Thus, memory extinction shares molecular mechanisms with learning, but the mechanisms of learning anew differ from those of learning the new.

Adrenergic beta-Antagonists↗
PubMed2000

The role of identified neurotransmitter systems in the response of insular cortex to unfamiliar taste: activation of ERK1-2 and formation of a memory trace.

In the behaving rat, the consumption of an unfamiliar taste activates the extracellular signal-regulated kinase 1-2 (ERK1-2) in the insular cortex, which contains the taste cortex. In contrast, consumption of a familiar taste has no effect. Furthermore, activation of ERK1-2, culminating in modulation of gene expression, is obligatory for the encoding of long-term, but not short-term, memory of the new taste (Berman et al., 1998). Which neurotransmitter and neuromodulatory systems are involved in the activation of ERK1-2 by the unfamiliar taste and in the long-term encoding of the new taste information? Here we show, by the use of local microinjections of pharmacological agents to the insular cortex in the behaving rat, that multiple neurotransmitters and neuromodulators are required for encoding of taste memory in cortex. However, these systems vary in the specificity of their role in memory acquisition and in their contribution to the activation of ERK1-2. NMDA receptors, metabotropic glutamate receptors, muscarinic, and beta-adrenergic and dopaminergic receptors, all contribute to the acquisition of the new taste memory but not to its retrieval. Among these, only NMDA and muscarinic receptors specifically mediate taste-dependent activation of ERK1-2, whereas the beta-adrenergic function is independent of ERK1-2, and dopaminergic receptors regulate also the basal level of ERK1-2 activation. The data are discussed in the context of postulated novelty detection circuits in the central taste system.

Adrenergic beta-Antagonists↗
PubMed1998

Specific and differential activation of mitogen-activated protein kinase cascades by unfamiliar taste in the insular cortex of the behaving rat.

Rats were given to drink an unfamiliar taste solution under conditions that result in long-term memory of that taste. The insular cortex, which contains the taste cortex, was then removed and assayed for activation of mitogen-activated protein kinase (MAPK) cascades by using antibodies to the activated forms of various MAPKs. Extracellular responsive kinase 1-2 (ERK1-2) in the cortical homogenate was significantly activated within <30 min of drinking the taste solution, without alteration in the total level of the ERK1-2 proteins. The activity subsided to basal levels within <60 min. In contrast, ERK1-2 was not activated when the taste was made familiar. The effect of the unfamiliar taste was specific to the insular cortex. Jun N-terminal kinase 1-2 (JNK1-2) was activated by drinking the taste but with a delayed time course, whereas the activity of Akt kinase and p38MAPK remained unchanged. Elk-1, a member of the ternary complex factor and an ERK/JNK downstream substrate, was activated with a time course similar to that of ERK1-2. Microinjection of a reversible inhibitor of MAPK/ERK kinase into the insular cortex shortly before exposure to the novel taste in a conditioned taste aversion training paradigm attenuated long-term taste aversion memory without significantly affecting short-term memory or the sensory, motor, and motivational faculties required to express long-term taste aversion memory. It was concluded that ERK and JNK are specifically and differentially activated in the insular cortex after exposure to a novel taste, and that this activation is required for consolidation of long-term taste memory.

Animals↗
PubMed1997

cAMP response element-binding protein in the amygdala is required for long- but not short-term conditioned taste aversion memory.

In conditioned taste aversion (CTA) organisms learn to avoid a taste if the first encounter with that taste is followed by transient poisoning. The neural mechanisms that subserve this robust and long-lasting association of taste and malaise have not yet been elucidated, but several brain areas have been implicated in the process, including the amygdala. In this study we investigated the role of amygdala in general, and the cAMP response element-binding protein (CREB) in the amygdala in particular, in CTA learning and memory. Toward that end, we combined antisense technology in vivo with behavioral, molecular, and histochemical analysis. Local microinjection of phosphorothioate-modified oligodeoxynucleotides (ODNs) antisense to CREB into the rat amygdala several hours before CTA training transiently reduced the level of CREB protein during training and impaired CTA memory when tested 3-5 d later. In comparison, sense ODNs had no effect on memory. The effect of antisense was not attributable to differential tissue damage and was site-specific. CREB antisense in the amygdala had no effect on retrieval of CTA memory once it had been formed, and did not affect short-term CTA memory. We propose that the amygdala, specifically the central nucleus, is required for the establishment of long-term CTA memory in the behaving rat; that the process involves long-term changes, subserved by CRE-regulated gene expression, in amygdala neurons; and that the amygdala may retain some CTA-relevant information over time rather than merely modulating the gustatory trace during acquisition of CTA.

Amygdala↗
PubMed1997

NMDA receptor and the tyrosine phosphorylation of its 2B subunit in taste learning in the rat insular cortex.

We demonstrate that the NMDA receptor is involved in taste learning in the insular cortex of the behaving rat and describe two facets of this involvement. Blockage of the NMDA receptor in the insular cortex by the reversible antagonist APV during training in a conditioned taste aversion (CTA) paradigm impaired CTA memory, whereas blockage of the NMDA receptor in an adjacent cortex or before a retrieval test had no effect. When rats sampled an unfamiliar taste and hence learned about it, either incidentally or in the context of CTA training, the tyrosine phosphorylation of the NMDA receptor subunit 2B (NR2B) in the insular cortex was specifically increased. The level of tyrosine phosphorylation on NR2B was a function of the novelty of the taste stimulus and the quantity of the taste substance consumed, properties that also determined the efficacy of the taste stimulus as a conditioned stimulus in CTA; however, blockage of the NMDA receptor by APV during training did not prevent tyrosine phosphorylation of NR2B. We suggest that tyrosine phosphorylation of NR2B subserves encoding of saliency in the insular cortex during the first hours after an unfamiliar taste is sampled and that this encoding is independent of another, necessary role of NMDA receptors in triggering experience-dependent modifications in the insular cortex during taste learning. Because a substantial fraction of the NR2B protein in the insular cortex seems to be expressed in interneurons, saliency and the tyrosine phosphorylation of NR2B correlated with it may modulate inhibition in cortex.

Animals↗
PubMed1996

Long-term potentiation increases tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit 2B in rat dentate gyrus in vivo.

Long-term potentiation (LTP) is a form of synaptic memory that may subserve developmental and behavioral plasticity. An intensively investigated form of LTP is dependent upon N-methyl-D-aspartate (NMDA) receptors and can be elicited in the dentate gyrus and hippocampal CA1. Induction of this type of LTP is triggered by influx of Ca2+ through activated NMDA receptors, but the downstream mechanisms of induction, and even more so of LTP maintenance, remain controversial. It has been reported that the function of NMDA receptor channel can be regulated by protein tyrosine kinases and protein phosphatases and that inhibition of protein tyrosine kinases impairs induction of LTP. Herein we report that LTP in the dentate gyrus is specifically correlated with tyrosine phosphorylation of the NMDA receptor subunit 2B in an NMDA receptor-dependent manner. The effect is observed with a delay of several minutes after LTP induction and persists in vivo for several hours. The potential relevance of this post-translational modification to mechanisms of LTP and circuit plasticity is discussed.

Amino Acid Sequence↗
PubMed1996

Carbachol mimics effects of sensory input on tyrosine phosphorylation in cortex.

We have recently shown that in the gustatory cortex of the rat, taste learning enhances protein tyrosine phosphorylation and taste memory is blocked by muscarinic antagonists. A major protein whose tyrosine phosphorylation is stimulated by taste learning in cortex is a 180 kDa synaptic glycoprotein identified as the NMDA receptor subunit 2B (NR2B). Here we report that microinjection of carbachol into the taste cortex modulates protein tyrosine phosphorylation similarly to the effect of unfamiliar taste, and that a 180 kDa protein whose tyrosine phosphorylation is enhanced in vivo by carbachol is NR2B. These data, combined with our previous findings, are in line with the hypothesis that muscarinic input plays a role in encoding new items in memory, and that tyrosine phosphorylation of NR2B is involved in this process.

Amino Acid Sequence↗
PubMed1996

Transient impairment of cholinergic function in the rat insular cortex disrupts the encoding of taste in conditioned taste aversion.

The muscarinic antagonist scopolamine blocks conditioned taste aversion (CTA) when microinjected bilaterally into the rat insular cortex shortly before the exposure of the rat to a novel taste (the conditioned stimulus, CS) in CTA training. Scopolamine has no effect when microinjected shortly after the exposure to the novel taste or shortly before the application of the malaise-inducing agent (unconditioned stimulus, UCS). Scopolamine does not affect sensory, motor and retrieval mechanisms required for performing the CTA task, and does not block CTA when injected into another cortical area. The effect of scopolamine is independent of the taste used as CS. Furthermore, microinjection of scopolamine into the insular cortex shortly before the pre-exposure to a new taste in a latent inhibition paradigm, impairs the attenuation of CTA by that pre-exposure. Other muscarinic antagonists, pirenzepine and AF DX-116, have an effect similar to that of scopolamine. Comparison of the dose-dependency curves of the muscarinic antagonists suggests a predominant role in CTA for M2 subtype receptors. Carbachol, a muscarinic agonist, also impairs the encoding of taste in the insular cortex, but the results are confounded by the ability of that ligand to induce seizures. Our findings suggest that cholinergic neuromodulation participates in processing the CS in the gustatory cortex in CTA, either by encoding novelty at the cellular level, or by instructing the neural circuits to store the novel taste representation.

Animals↗
PubMed1996

Flavor and the frontal cortex.

Rats were trained to discriminate an aqueous compound of an odor and taste (amyl acetate and NaCl) from the components of the compound before removal of one olfactory bulb and the contralateral ventrolateral frontal cortex. In postoperative tests, experimental rats performed much more poorly than nonlesioned controls or controls which had all lesions made in the same hemisphere. However, there were no significant differences among groups on tests for detection of amyl acetate and NaCl. These results provide evidence that integration of taste and smell in the production of flavor occurs in the ventrolateral frontal cortex.

Animals↗
PubMed1995

Differential modulation of brain immediate early genes by intraperitoneal LiCl.

We have used in situ hybridization to investigate the modulation of expression of the immediate early genes (IEGs) c-fos, fos-B, zif/268 and CREM in rat brain following oral administration of saccharin, i.p. injection of LiCl, and conditioned taste aversion (CTA) training in which these stimuli are used as the conditioned stimulus (CS) and the unconditioned stimulus (UCS), respectively. Modulation of c-fos, zif/268 and CREM was detected in the NTS, PBN, hypothalamic PVN and central nucleus of the amygdala after the administration of the UCS but not the CS. Our data are consonant with the hypothesis that differential and combinatorial expression of IEGs plays a role in encoding the representation of LiCl-induced malaise in the brain.

Animals↗
PubMed1995

Modulation of protein tyrosine phosphorylation in rat insular cortex after conditioned taste aversion training.

Protein tyrosine phosphorylation is a major signal transduction pathway involved in cellular metabolism, growth, and differentiation. Recent data indicate that tyrosine phosphorylation also plays a role in neuronal plasticity. We are using conditioned taste aversion, a fast and robust associative learning paradigm subserved among other brain areas by the insular cortex, to investigate molecular correlates of learning and memory in the rat cortex. In conditioned taste aversion, rats learn to associate a novel taste (e.g., saccharin) with delayed poisoning (e.g., by LiCl injection). Here we report that after conditioned taste aversion training, there is a rapid and marked increase in tyrosine phosphorylation of a set of proteins in the insular cortex but not in other brain areas. A major protein so modulated, of 180 kDa, is abundant in a membrane fraction and remains modulated for more than an hour after training. Exposure of the rats to the novel taste alone results in only a small modulation of the aforementioned proteins whereas administration of the malaise-inducing agent per se has no effect. To the best of our knowledge, this is the first demonstration of modulation of protein tyrosine phosphorylation in the brain after a behavioral experience.

Animals↗
PubMed1994

Overexpression of urokinase-type plasminogen activator in transgenic mice is correlated with impaired learning.

Transgenic mice designated alpha MUPA overproduce in the brain murine urokinase-type plasminogen activator (uPA), an extracellular protease implicated in tissue remodeling. We have now localized, by in situ hybridization, extensive signal of uPA mRNA in the alpha MUPA cortex, hippocampus, and amygdala, sites that were not labeled in counterpart wild-type mice. Furthermore, biochemical measurements reveal a remarkably high level of enzymatic activity of uPA in the cortex and hippocampus of alpha MUPA compared with wild-type mice. We have used the alpha MUPA mice to examine whether the abnormal level of uPA in the cortex and the limbic system affects learning ability. We report that alpha MUPA mice perform poorly in tasks of spatial, olfactory, and taste-aversion learning, while displaying normal sensory and motor capabilities. Our results suggest that uPA is involved in neural processes subserving a variety of learning types.

Animals↗