Learning & Memory

The misinformation effect refers to the impairment in memory for the past that arises after exposure to misleading information. The phenomenon has been investigated for at least 30 years, as investigators have addressed a number of issues. These include the conditions under which people are especially susceptible to the negative impact of misinformation, and conversely when are they resistant. Warnings about the potential for misinformation sometimes work to inhibit its damaging effects, but only under limited circumstances. The misinformation effect has been observed in a variety of human and nonhuman species. And some groups of individuals are more susceptible than others. At a more theoretical level, investigators have explored the fate of the original memory traces after exposure to misinformation appears to have made them inaccessible. This review of the field ends with a brief discussion of the newer work involving misinformation that has explored the processes by which people come to believe falsely that they experienced rich complex events that never, in fact, occurred.

A quantitative computational theory of the operation of the CA3 system as an attractor or autoassociation network is described. Based on the proposal that CA3-CA3 autoassociative networks are important for episodic or event memory in which space is a component (place in rodents and spatial view in primates), it has been shown behaviorally that the CA3 supports spatial rapid one-trial learning and learning of arbitrary associations and pattern completion where space is a component. Consistent with the theory, single neurons in the primate CA3 respond to combinations of spatial view and object, and spatial view and reward. Furthermore, single CA3 neurons reflect the recall of a place from an object in a one-trial object-place event memory task. CA3 neurons also reflect in their firing a memory of spatial view that is retained and updated by idiothetic information to implement path integration when the spatial view is obscured. Based on the computational proposal that the dentate gyrus produces sparse representations by competitive learning and via the mossy fiber pathway forces new representations on the CA3 during learning (encoding), it has been shown behaviorally that the dentate gyrus supports spatial pattern separation during learning, and that the mossy fiber system to CA3 connections are involved in learning but not in recall. The perforant path input to CA3 is quantitatively appropriate to provide the cue for recall in CA3. The concept that the CA1 recodes information from CA3 and sets up associatively learned back-projections to neocortex to allow subsequent retrieval of information to neocortex provides a quantitative account of the large number of hippocampo-neocortical back-projections.

Protein synthesis is involved in the consolidation of short-term memory into long-term memory. Previous electrophysiological data concerning LTP in CA3 suggest that protein synthesis in that region might also be necessary for short-term memory. We tested this hypothesis by locally injecting the protein synthesis inhibitor anisomycin in hippocampal area CA1 or CA3 immediately after contextual fear conditioning. As previously shown, injections in CA1 impaired long-term memory but spared short-term memory. Conversely, injections in CA3 impaired both long-term and short-term memories. We conclude that early steps of experience-induced plasticity occurring in CA3 and underlying short-term memory require protein synthesis.

How does the time of day of a practice session affect learning of a new motor sequence in the elderly? Participants practiced a given finger tapping sequence either during morning or evening hours. All participants robustly improved performance speed within the session concurrent with a reorganization of the tapping pattern of the sequence. However, evening-trained participants showed additional gains overnight and at 1 wk posttraining; moreover, evening training led to a further reorganization of the tapping pattern offline. A learning experience preceding nocturnal sleep can lead to a task-specific movement routine as an expression of novel “how to” knowledge in the elderly.

Fear extinction refers to the ability to adapt as situations change by learning to suppress a previously learned fear. This process involves a gradual reduction in the capacity of a fear-conditioned stimulus to elicit fear by presenting the conditioned stimulus repeatedly on its own. Fear extinction is context-dependent and is generally considered to involve the establishment of inhibitory control of the prefrontal cortex over amygdala-based fear processes. In this paper, we review research progress on the neural basis of fear extinction with a focus on the role of the amygdala and the prefrontal cortex. We evaluate two competing hypotheses for how the medial prefrontal cortex inhibits amygdala output. In addition, we present new findings showing that lesions of the basal amygdala do not affect fear extinction. Based on this result, we propose an updated model for integrating hippocampal-based contextual information with prefrontal-amygdala circuitry.

Fear extinction refers to the ability to adapt as situations change by learning to suppress a previously learned fear. This process involves a gradual reduction in the capacity of a fear-conditioned stimulus to elicit fear by presenting the conditioned stimulus repeatedly on its own. Fear extinction is context-dependent and is generally considered to involve the establishment of inhibitory control of the prefrontal cortex over amygdala-based fear processes. In this paper, we review research progress on the neural basis of fear extinction with a focus on the role of the amygdala and the prefrontal cortex. We evaluate two competing hypotheses for how the medial prefrontal cortex inhibits amygdala output. In addition, we present new findings showing that lesions of the basal amygdala do not affect fear extinction. Based on this result, we propose an updated model for integrating hippocampal-based contextual information with prefrontal-amygdala circuitry.

This chapter deals with the construction of linguistic, geographical, and pragmatic spaces in early modern Latin translations of vernacular literature. The first part discusses the constructed spaces in early modern Latinity, introducing three intellectual concepts: res publica litterarum, Europa nostra, and translatio linguae et studii. All of them convey the idea of an ample common space in which Latin, as a common ground, lingua franca, and intermediary language, is the appropriate vehicle for cultural contact.
These points are made more tangible using a case study: Tommaso Campanella’s philosophical dialogue Civitas Solis (La Città del Sole). An analysis of the first printed edition (1623) contextualizes the paratextual framing, particularly the bell metaphor (Campanula) within the dedicatory poem, and its implications for the conceptualization of the Latin translation, allowing some conclusions regarding media changes, visibility, and authorial control in Latin translations.

Keywords: Latinization, res publica litterarum, Europa nostra, translatio studii, Campanella

Two experiments using rats in a contextual fear memory preparation compared two approaches to reduce conditioned fear: 1) pharmacological reconsolidation blockade and 2) reactivation-plus-extinction training. In experiment 1 we explored different combinations of reactivation-plus-extinction parameters to reduce conditioned fear and attenuate reacquisition. In experiment 2, memory reactivation was followed by extinction training, or administration of Midazolam (vs vehicle) to reduce conditioned fear and attenuate spontaneous recovery. We found both treatments to be equally effective in both experiments. This study suggests that parameters leading to memory destabilization during reactivation are critical to observe long-lasting effects of MDZ or reactivation-plus-extinction.

It is known that a consolidated memory can return to a labile state and become transiently malleable following reactivation. This instability is followed by a restabilization phase termed reconsolidation. In this work, we explored whether an unrelated appetitive experience (voluntary consumption of diluted sucrose) can affect a contextual fear memory in rats during the reactivation-induced destabilization phase. Our findings show that exposure to an appetitive experience following reactivation can diminish fear retention. This effect persisted after 1 wk. Importantly, it was achieved only under conditions that induced fear memory destabilization. This result could not be explained as a potentiated extinction, because sucrose was unable to promote extinction. Since GluN2B-containing NMDA receptors in the basolateral amygdala complex (BLA) have been implicated in triggering fear memory destabilization, we decided to block pharmacologically these receptors to explore the neurobiologica...

It has been suggested that, unlike pure extinction which typically results in the return of the fear response under a variety of circumstances, memory reactivation followed by extinction can attenuate the reemergence of conditioned fear. The reactivation–extinction procedure has attracted the attention of basic and clinical researchers due to its potential clinical value for the treatment of psychiatric conditions, such as anxiety and drug abuse disorders. However, mixed results have been achieved so far in replicating and understanding this paradigm. It has been proposed that memory destabilization could be critical in this sense. Using contextual fear conditioning in rats and midazolam as an amnesic agent, we first determined what reactivation conditions are necessary to destabilize the mnemonic trace. After establishing the conditions for memory destabilization, a series of experiments was conducted to determine if destabilization is critical for the success of the reactivation–e...

Social interaction is essential for life but is impaired in many psychiatric disorders. We presently focus on rats with a truncated allele for dopamine transporter (DAT). Since heterozygous individuals possess only one non-mutant allele, epigenetic interactions may unmask latent genetic predispositions. Homogeneous “maternal” heterozygous offspring (termed MAT-HET) were born from dopamine-transporter knocked-out (DAT-KO) male rats and wild-type (WT) mothers; “mixed” heterozygous offspring (termed MIX-HET) were born from both DAT-heterozygous parents. Their social behavior was assessed by: partner-preference (PPT), social-preference (SPT) and elicited-preference (EPT) tests. During the PPT, focal MIX-HET and MAT-HET males had a choice between two WT females, one in estrous and the other not. In the SPT, they met as stimulus either a MIX-HET or a WT male. In the EPT, the preference of focal male WT rats towards either a MIX- or a MAT-HET stimulus was tested. MIX-HET focal males showed...

Here, we examine effects of the steroid hormone, 20-hydroxyecdysone (20-E), on associative olfactory learning in the honeybee, Apis mellifera. 20-E impaired the bees’ ability to associate odors with punishment during aversive conditioning, but did not interfere with their ability to associate odors with a food reward (appetitive learning). The steroid had a significant impact also on the expression of amine-receptor genes in centers of the brain involved in the formation and recall of associative olfactory memories (mushroom bodies). 20-E increased expression of the dopamine receptor gene, Amdop2, and reduced the expression of the putative dopamine/ecdysone receptor gene, Amgpcr19. Interestingly, Amgpcr19 tended to be highly expressed in the brains of foragers that exhibited strong aversive learning, but expressed at lower levels in bees that performed well in appetitive learning assays. In 2-d-old bees, transcript levels of the same gene could be reduced by queen mandibular pheromo...

Adenosine A 1 and cannabinoid CB 1 receptors are affected by drugs widely consumed by humans, as it is the case for caffeine, an adenosine receptor antagonist, and tetrahydrocannabinol, a cannabinoid receptor agonist. These receptors are present in the hippocampus and inhibit neurotransmitter release by operating similar transduction mechanisms. We, therefore, evaluated if they cross-talk to modulate synaptic transmission in the hippocampus. To do so, field excitatory postsynaptic potentials (fEPSPs) were recorded from the CA1 area of rat hippocampal slices and the consequences of activation or blockade of cannabinoid CB 1 or adenosine A 1 receptors upon neuromodulation exerted by the other receptor were assessed. The cannabinoid CB 1 receptor agonist, WIN55212-2 (300 nM), slowly decreased (≅ 40%) the fEPSP slope, while the adenosine A 1 receptor agonist, cyclopenthyladenosine (CPA, 15 nM) rapidly decreased (≅ 50%) it. Blockade of cannabinoid CB 1 receptors with AM251 (1 µM) did not influence the adenosine A 1 receptor-mediated inhibition of synaptic transmission. Blockade of adenosine A 1 receptors with 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 50 nM) did not affect the inhibition perpetrated by cannabinoid CB 1 receptor activation. When both receptors were simultaneously activated (5 nM CPA plus 300 nM WIN55212-2) the net inhibition of synaptic transmission was about the sum of the effect of each drug applied independently. These results indicate independent synaptic transmission modulation by adenosine A 1 and cannabinoid CB 1 receptors at the hippocampus, suggesting that availability of G-proteins coupled to each receptor and availability of other signalling molecules involved in their transducing pathways, are not limiting factors for their modulatory role.

A cue presented during Pavlovian extinction may help the recovery of the extinction memory, for which is called an extinction cue (EC). Pavlovian conditioning has been useful as a model of different behavior disorders and extinction as a model for their treatment. Extinguished responses may be recovered under different circumstances, akin to a relapse. Hence, it is important to strengthen extinction memory retrieval. There is contradictory evidence of the effectiveness of ECs to this end. There is also little information about the magnitude of response recovery prevention when using ECs. The magnitude of the ECs effect on response recovery was analyzed by a meta-analysis that considered possible sources of variance in the EC effect. The included studies were gathered mainly through scientific database search engines. Selection criteria included experiments that used a Pavlovian extinction and recovery procedure with an EC test. Effect size was calculated for each relevant experiment...

The role of the associative connections in the propagation of epileptiform discharges originating from an acute, localized epileptic focus in the anterior piriform cortex has been characterized recently in the in vitro isolated guinea-pig brain preparation. The present study demonstrates that the dorsal propagation of epileptiform synaptic potentials generated in APC is carried by long-projective associative fibres. Current source density analysis of the field potential profiles evoked by stimulation of the lateral olfactory tract has been utilized to describe the functional circuit activated in rostral and caudal regions of the piriform cortex, before and after the induction of a bicuculline epileptic focus in the anterior piriform cortex. Separate stimulation of ~!he lateral olfactory tract at two sites, caudal and rostral to a tract incision, activates epileptiform potentials that are generated at the site of primary focus in the anterior piriform cortex and travel along associative fibres. Selective cutting of the long-projective associative fibres abolishes the epileptic associative potential in the cortical regions caudal to the section. The present study demonstrates directly that epileptiform potentials propagate along associative fibres to cortical regions that are synaptically related to the focus of origin. Such a pattern of propagation may sustain the generation of secondary foci in cortical regions remote from the primary epileptic focus.

Relaxin-3 has been proposed to modulate emotional-behavioural functions such as arousal and behavioural activation, appetite regulation, stress responses, anxiety, memory, sleep and circadian rhythm. The nucleus incertus (NI), in the midline tegmentum close to the fourth ventricle, projects widely throughout the brain and is the primary site of relaxin-3 neurons. Over recent years, a number of preclinical studies have explored the function of the NI and relaxin-3 signalling, including reports of mRNA or peptide expression changes in the NI in response to behavioural or pharmacological manipulations, effects of lesions or electrical or pharmacological manipulations of the NI, effects of central microinfusions of relaxin-3 or related agonist or antagonist ligands on physiology and behaviour, and the impact of relaxin-3 gene deletion or knockdown. Although these individual studies reveal facets of the likely functional relevance of the NI and relaxin-3 systems for human physiology and ...

Continuous presentation of an olfactory stimulus causes a decrement of the chemotaxis response in the nematode Caenorhabditis elegans. However, the differences between the learning process of habituation (a readily reversible decrease in behavioral response) and other types of olfactory plasticity such as adaptation (a decrement in response due to sensory fatigue, which cannot be dishabituated) have not been addressed. The volatile odorant diacetyl (DA) was used within a single paradigm to assess the distinct processes of olfactory adaptation and habituation. Preexposing and testing worms to 100% DA vapors caused a chemotaxis decrement that was not reversible despite the presentation of potentially dishabituating stimuli. This DA adaptation was abolished in worms with an odr-10 mutation (encoding a high-affinity DA receptor on the AWA neuron), even though naive chemotaxis remained unaffected. Conversely, DA adaptation remained intact in odr-1 mutants (defective in AWC neuron-mediate...

Continuous presentation of an olfactory stimulus causes a decrement of the chemotaxis response in the nematode Caenorhabditis elegans. However, the differences between the learning process of habituation (a readily reversible decrease in behavioral response) and other types of olfactory plasticity such as adaptation (a decrement in response due to sensory fatigue, which cannot be dishabituated) have not been addressed. The volatile odorant diacetyl (DA) was used within a single paradigm to assess the distinct processes of olfactory adaptation and habituation. Preexposing and testing worms to 100% DA vapors caused a chemotaxis decrement that was not reversible despite the presentation of potentially dishabituating stimuli. This DA adaptation was abolished in worms with an odr-10 mutation (encoding a high-affinity DA receptor on the AWA neuron), even though naive chemotaxis remained unaffected. Conversely, DA adaptation remained intact in odr-1 mutants (defective in AWC neuron-mediated olfactory behavior), even though naive chemotaxis to DA decreased. Surprisingly, exposure to vapors of intermediate concentrations of DA (0.01% and 25%) did not cause worms to exhibit any response decrement. In contrast to preexposure to high DA concentrations, preexposure to low DA concentrations (0.001%) produced habituation of the chemotaxis response (a dishabituating stimulus could reverse the response decrement back to baseline levels). The distinct behavioral effects produced by DA preexposure highlight a concentration-dependent dissociation between two decremental olfactory processes: adaptation at high DA concentrations versus habituation at low DA concentrations.

Ira Hirsh was among the first to recognize that the auditory system does not deal with temporal information in a unitary way across the continuum of time intervals involved in speech processing. He identified the short range (extending from 1 to 20 milliseconds) as that of phase perception, the range between 20 and 100 milliseconds as that in which auditory patterns emerge, and the long range from 100 milliseconds and longer as that of separate auditory events. Furthermore, he also was among the first to recognize that auditory time perception heavily depended on spectral context. A study of the perception of sequences representing different temporal orders of three tones, by Hirsh and the author (e.g., Divenyi and Hirsh, 1978) demonstrated the dependence of auditory sequence perception on both time range and spectral context, and provided a bridge between Hirsh's view of auditory time and Bregman's view of stream segregation. A subsequent search by the author for psychophys...

Dual-process theory, which holds that recognition decisions can be based on recollection or familiarity, has long seemed incompatible with signal detection theory, which holds that recognition decisions are based on a singular, continuous memory-strength variable. Formal dual-process models typically regard familiarity as a continuous process (i.e., familiarity comes in degrees), but they construe recollection as a categorical process (i.e., recollection either occurs or does not occur). A continuous process is characterized by a graded relationship between confidence and accuracy, whereas a categorical process is characterized by a binary relationship such that high confidence is associated with high accuracy but all lower degrees of confidence are associated with chance accuracy. Using a source-memory procedure, we found that the relationship between confidence and source-recollection accuracy was graded. Because recollection, like familiarity, is a continuous process, dual-process theory is more compatible with signal detection theory than previously thought.

A series of experiments used rats to study the effect of a systemic or intra-amygdala infusion of the benzodiazepine, midazolam, on learning and re-learning to inhibit context conditioned fear (freezing) responses. Rats were subjected to two context-conditioning episodes followed by extinction under drug or vehicle, or to two cycles of context conditioning and extinction with the second extinction under drug or vehicle. A 20-min extinction under vehicle resulted in better long-term inhibition on a subsequent drug-free retention test than a 4-min extinction under vehicle, or a 20-min, as well as a 4-min, extinction under drug. However, a 20-min, as well as a 4-min, second extinction under drug was just as effective in producing long-term inhibition as a 20-min second extinction under vehicle and this inhibition was greater than that produced by a 4-min second extinction under vehicle. Initial extinction of 5, 10, or 20 min were equally effective in producing long-term inhibition when...

Gene expression is a key process for memory consolidation. Recently, the participation of epigenetic mechanisms like histone acetylation was evidenced in long-term memories. However, until now the training strength required and the persistence of the chromatin acetylation recruited are not well characterized. Here we studied whether histone acetylation is involved in consolidation in invertebrates, whether it depends on the training strength, and whether it is a permanent or transient mechanism. We used a well-characterized memory model in invertebrates, the context-signal memory in crabs. Our results show no changes in histone 3 (H3) acetylation during consolidation of a standard training protocol. However, strong training induced a significant increase in H3 acetylation 1-h post-training, returning to basal levels afterward. Accordingly, the administration of histone deacetylase inhibitors sodium butyrate (NaB) and trichostatin A allowed a weak training to induce long-term memory. NaB enhanced memory in two phases during consolidation. These findings support that H3 acetylation (1) is involved in consolidation, (2) occurs only after strong training, (3) is a transient process, and (4) memory is enhanced in two phases. The coincidence of these phases with other mechanisms of gene expression is discussed.

It is assumed that the claustrum (CL) is involved in sensorimotor integration and cognitive processes. We recorded the firing activity of identified CL neurons during classical eyeblink conditioning in rabbits, using a delay paradigm in which a tone was presented as conditioned stimulus (CS), followed by a corneal air puff as unconditioned stimulus (US). Neurons were identified by their activation from motor (MC), cingulate (CC), and medial prefrontal (mPFC) cortices. CL neurons were rarely activated by single stimuli of any modality. In contrast, their firing was significantly modulated during the first sessions of paired CS/US presentations, but not in well-trained animals. Neuron firing rates did not correlate with the kinematics of conditioned responses (CRs). CL local field potentials (LFPs) changed their spectral power across learning and presented well-differentiated CL-mPFC/CL-MC network dynamics, as shown by crossfrequency spectral measurements. CL electrical stimulation did not evoke eyelid responses, even in trained animals. Silencing of synaptic transmission of CL neurons by the vINSIST method delayed the acquisition of CRs but did not affect their presentation rate. The CL plays an important role in the acquisition of associative learning, mostly in relation to the novelty of CS/US association, but not in the expression of CRs.

This chapter addresses the question, Has the methodology of cross-modal transfer effected our theory of cognition and blindness to the detriment of the majority of people with visual impairments? In order to address this question, philosophical and psychological literature in the date range 1688-2008 is surveyed, and methodologies are analysed using an epistemological model of blindness. It is concluded that methodologies used in the study of cross-modal transfer rarely developed a useful epistemology of blindness, or promoted the social inclusion of people with visual impairments. Instead, studies often conflated moral philosophy, intellect and perception for political and religious motives. Two possible solutions to these problems are suggested: firstly, methodology in the study of philosophy and psychology needs to accommodate a spectrum of variables effecting visual impairment; secondly, philosophers and psychologists need to do more to promote the inclusion and understanding of blindness itself, rather than trying to make broad points about the mind and deficit.

Educational practice does not, for the most part, rely on research findings. Instead, there's a preference for relying on our intuitions about what's best for learning. But relying on intuition may be a bad idea for teachers and learners alike.

Retrograde amnesia following disruptions of hippocampal function is often temporally graded, with recent memories being more impaired. Evidence supports the existence of one or more neocortical long-term memory storage/retrieval site(s). Neurotoxic lesions of the medial prefrontal cortex (mPFC) or the dorsal hippocampus (DH) were made 1 day or 200 days following trace fear conditioning. Recently encoded trace fear memories were most disrupted by DH lesions, while remotely encoded trace and contextual memories were most disrupted by mPFC lesions. These data strongly support the consolidation theory of hippocampus function and implicate the mPFC as a site of long-term memory storage/retrieval.

Conditioning the proboscis extension reflex of harnessed honeybees (Apis mellifera) is used to study the effect temporal spacing between successive conditioning trials has on memory. Retention is monitored at two long-term intervals corresponding to early (1 and 2 d after conditioning) and late long-term memory (3 and 4 d). The acquisition level is varied by using different conditioned stimuli (odors, mechanical stimulation, and temperature increase at the antenna), varying strengths of the unconditioned stimulus (sucrose), and various numbers of conditioning trials. How learning trials are spaced is the dominant factor both for acquisition and retention, and although longer intertrial intervals lead to better acquisition and higher retention, the level of acquisition per se does not determine the spacing effect on retention. Rather, spaced conditioning leads to higher memory consolidation both during acquisition and later, between the early and long-term memory phases. These consol...

A memory-based processing approach to discourse comprehension emphasizes the rapid deployment of information in memory to facilitate understanding of the text that is currently being read. S. B. Greene, R. J. Gerrig, G. demonstrated that when a text described the reunion of 2 characters who had previously discussed a 3rd character, the accessibility of the 3rd character increased, and the use of an unheralded pronoun (R. J. to refer to that character was felicitous. In experiments in this article, the authors demonstrate that concepts related to the referent of the unheralded pronoun also increase in accessibility and that those concepts form associations in memory with concepts present in the discourse at the time the pronoun is used. The authors also show that the increase in accessibility for the referent of the pronoun, as well as the appropriate long-term memory associations, occurs even in the absence of the pronoun. A New Yorker profile of Supreme Court Justice Clarence Thomas described a scene in which Thomas limped on stage to appear on a conservative talk show with host Mark Larson (Toobin, 1993). The studio audience applauded enthusiastically as Thomas, already on crutches from his basketball accident, squeezed past Larson to make his way to his designated position in front of the camera. As Thomas hobbled by, Larson 'quipped, "I know what people are thinking fight now: Boy, the Committee was really tough with those hearings, and now this .... "As Thomas settled into place, Larson said, "She just won't let up, will she?" (p. 45). Who is she? Members of the audience were certainly meant to know as the article went on to say" 'She just won't let up, will she?' " There was no need to use the name. Even two years later, even in front of the Justice's friends, Anita Hill remained the ever-present "She" in Clarence Thomas's life (Toobin, 1993, p. 45). We have labeled pronouns like Larson's "she" unheralded pronouns . What sets unheralded pronouns apart from run-of-themill pronouns is that their referents cannot be found in the immediate discourse environment. Larson used she without an explicit, local, linguistic antecedent. For the audience to

We examined the effects of both the metabotropic glutamate receptor (mGluR) antagonist MCPG and the agonist tADA in two behavioral paradigms in rats: (1) brightness discrimination and (2) spatial alternation. Compounds were applied intracerebroventricularly at different times, either 30 min prior to training or immediately after training, and rats were tested for retention 24 hr later in the same paradigms. Both MCPG and tADA caused amnesia in the spatial alternation test, when applied pretraining, but no effect was obtained in the brightness discrimination paradigm. Drug-induced amnesia was shown not to be attributable to state-dependent effects of MCPG or tADA. Moreover, the memory inhibiting effect of MCPG was dose dependent, with a low dose (20 raM/5 ml) having no effect on learning and memory and a 10 times higher concentration (200 mM/5 ml) causing complete amnesia. Application of both saline and MCPG immediately post-training prevented memory formation, which may be attributable to an interference by the injection procedure with the process of memory formation. The mGluR agonist tADA, however, facilitated memory formation in the spatial alternation task, when injected immediately after training.

Metabotropic glutamate receptors (mGluRs) have been implicated in long-term potentiation and in learning and memory formation. In this study, we tested the effects of group I mGluR inhibition on synaptic plasticity and learning of rats at different levels of organization (1) in the hippocampal slice preparation; (2) in freely moving animals implanted with chronic hippocampal electrodes; and (3) in different spatial learning paradigms. To allow a direct comparison of the effects obtained the same doses were used in all paradigms. Bath-application of the selective group I mGluR antagonist (S)4-carboxyphenylglycine (4-CPG) impaired a decremental long-term potentiation (LTP) induced by a weak tetanization paradigm, but failed to affect a robust LTP generated by strong tetanization. In contrast, 4-CPG impaired a robust LTP in freely moving animals if applied 30 min before tetanization. The same dose of 4-CPG only impeded spatial learning mildly in the eight-arm radial maze and had no effect on a simple configuration of the Y-maze spatial alternation task. In the more difficult configuration of this task, however, 4-CPG caused complete amnesia. The lack of state-dependent 4-CPG actions and the absence of any 4-CPG effects in the open-field test classify the obtained retention deficit as a selective impairment of memory storage. Our results indicate a specific role of group I mGluRs in certain types of synaptic plasticity and of spatial learning.

Massed training is less effective for long-term memory formation than the spaced training. The role of acetylation in synaptic plasticity and memory is now well established. However, the role of this important protein modification in synaptic plasticity induced by massed pattern of stimulation or memory induced by massed training is not well understood. Here we show that increasing the level of acetylation enhances long-term potentiation induced by massed pattern of high frequency stimulation. Furthermore, enhancing acetylation level facilitates long-term memory by massed training. Thus, increasing acetylation level facilitates synaptic plasticity and memory by massed patterns.

Humans routinely use past experience with complexity to deal with novel, challenging circumstances. This fundamental aspect of real-world behavior has received surprisingly little attention in animal studies, and the underlying brain mechanisms are unknown. The present experiments tested for transfer from past experience in rats and then used quantitative imaging to localize synaptic modifications in hippocampus. Six daily exposures to an enriched environment (EE) caused a marked enhancement of short- and long-term memory encoded during a 30-min session in a different and complex environment relative to rats given extensive handling or access to running wheels. Relatedly, the EE animals investigated the novel environment in a different manner than the other groups, suggesting transfer of exploration strategies acquired in earlier interactions with complexity. This effect was not associated with changes in the number or size of excitatory synapses in hippocampus. Maps of synapses exp...

BDNF-induced signaling is essential for the development of the central nervous system and critical for plasticity in adults. Mature BDNF signals through TrkB, while its precursor proBDNF employs p75NTR, resulting in activation of signaling cascades with opposite effects on neuronal survival, growth cone decisions, and synaptic plasticity. Accordingly, variations in the genes encoding BDNF and its receptors sometimes have opposing influences in psychiatric disorders, and despite the vast literature, consensus is lacking about the behavioral consequences of disrupting the activity of the BDNF system in mice. To dissect the behavioral traits affected by dysfunctional BDNF/TrkB vs. proBDNF/p75NTR activity, we studied Bdnf+/−, Ntrk2+/−, and Ngfr−/− mice in parallel with respect to exploratory behavior, anxiety, startle, and fear acquisition. Our data reveal that the effect of proBDNF/BDNF and its receptors on behavior is more complex than expected. Strikingly, receptor-deficient mice dis...

Aunque no aparece literalmente en dicho artículo, actúa como una luz interpretativa al mostrar que la bienaventuranza esencial, es decir, la felicidad, no consiste en un acto de la voluntad, sino en un acto del intelecto. La voluntad participa de esa felicidad, sí, pero de manera consecuente, como fruición o deleite del bien que ha sido conocido y poseído por el intelecto -no como la esencia de la bienaventuranza, es decir, de la misma felicidad. Esta afirmación de Santo Tomás de Aquino no es simplemente una proposición metafísica; constituye un pilar fundamental para toda reflexión seria sobre el bienestar humano, especialmente cuando se la pone en diálogo con la psicología. En una época en la que la felicidad ha sido frecuentemente reducida a estados emocionales pasajeros, a la estimulación sensorial o a la elevación hormonal, esta máxima tomista nos invita a una reordenación profunda: la felicidad no se encuentra en el cuerpo, sino que comienza por la claridad del alma. De hecho, como nos recuerda el Aquinate, el ser humano está compuesto de cuerpo y alma, pero su forma sustancial -aquello que da el ser al cuerpo como cuerpo humano-es el alma racional. Por eso, aunque la felicidad involucre, sí, efectos psicofísicos, jamás puede ser reducida a ellos sin perder su esencia. La verdadera felicidad es un acto de la inteligencia que reconoce y capta el bien verdadero. Cuando esa ordenación se rompe, el hombre queda dominado por las potencias inferiores del alma, buscando en placeres pasajeros lo que solo puede encontrarse en la posesión ordenada del bien. Y esto genera confusión, dolor, ansiedad, desorden y tantos otros males. En el ámbito clínico, ese desequilibrio se percibe a diario. El paciente que entra en consulta muchas veces sufre porque está desordenado interiormente. Se encuentra sometido al imperio de los sentidos, guiado por afectos, impulsos y emociones no educadas ni ordenadas, como si la felicidad consistiera únicamente en "sentirse bien". Sin embargo, una vida regulada por tales criterios es inestable, frágil y fácilmente manipulable, ya que todo depende de lo exterior y de las circunstancias. Santo Tomás dedica toda una cuestión, con varios artículos 1 , a afirmar que la felicidad del hombre no está en las riquezas, ni en el honor, ni en la gloria, ni en el poder, ni en los bienes del cuerpo, ni siquiera en el placer, sino en la operación del alma conforme a la virtud y, principalmente, en la contemplación de la verdad. Esta comprensión es vital para la práctica clínica orientada por una antropología verdadera. La Psicoterapia Tomista busca restaurar el gobierno de la inteligencia sobre el hombre interior. Se trata de reconducir a la persona hacia su estructura natural: donde la

Research on expertise suggests that a critical aspect of expert understanding is knowledge of the relations between domain principles and problem features. We investigat-ed two instructional pathways hypothesized to facilitate students ’ learning of these relations when studying worked examples. The first path is through self-explaining how worked examples instantiate domain principles and the second is through analogical comparison of worked examples. We compared both of these pathways to a third instructional path where students read worked examples and solved practice problems. Students in an introductory physics class were randomly assigned to one of three worked example conditions (reading, self-explanation, or analogy) when learning about rotational kinematics and then completed a set of problem solving and conceptual tests that measured near, intermediate, and far transfer. Students in the reading and self-explanation groups performed better than the analogy group on near tra...

I hereby certify that I am the sole author of this thesis and that no part of this thesis has been published or submitted for publication. I certify that, to the best of my knowledge, my thesis does not infringe upon anyone"s copyright nor violate any proprietary rights and that any ideas, techniques, quotations, or any other material from the work of other people included in my thesis, published or otherwise, are fully acknowledged in accordance with the standard referencing practices. Furthermore, to the extent that I have included copyrighted material that surpasses the bounds of fair dealing within the meaning of the Canada Copyright Act, I certify that I have obtained a written permission from the copyright owner(s) to include such material(s) in my thesis and have included copies of such copyright clearances to my appendix. I declare that this is a true copy of my thesis, including any final revisions, as approved by my thesis committee and the Graduate Studies office, and that this thesis has not been submitted for a higher degree to any other University or Institution.

Although subjective memory complaints are one of the most common causes behind visits to health services, there are hardly any validated instruments in Spanish for evaluating their magnitude. Since memory complaint questionnaires usually include items referring to attentional and executive aspects, it has been hypothesised that they may well be related with other processes that depend on the integrity of the prefrontal cortex. Aim. The purpose of this study was to examine the psychometric properties of an instrument based on the Memory Failures in Everyday (MFE) questionnaire, thus providing a valuation over a broad sample of the Spanish population. A second aim of the study was to analyse the relations that exist between the appearance of the complaints, the symptoms of a prefrontal origin and perceived stress. The MFE-30 (a modified version of the MFE), the dysexecutive questionnaire and the perceived stress scale were administered to a sample of young adults from a non-clinical general population (n = 900). Results. The analyses show that the MFE-30 is a single-factor questionnaire that evaluates a single construct called 'cognitive complaints'. Moreover, an intense pattern of correlations among these complaints, the symptoms of a prefrontal origin and perceived stress is observed. The resulting scores show that the MFE-30 is a useful instrument in clinical practice. Findings are in line with those from previous studies, thus suggesting that there is a close relation among the appearance of cognitive complaints, the presence of prefrontal symptoms and perceived stress.

This research is an investigation of whether consciousness—one’s ongoing experience—influences one’s behavior and, if so, how. Analysis of the components, structure, properties, and temporal sequences of consciousness has established that, (1) contrary to one’s intuitive understanding, consciousness does not have an active, executive role in determining behavior; (2) consciousness does have a biological function; and (3) consciousness is solely information in various forms. Consciousness is associated with a flexible response mechanism (FRM) for decision-making, planning, and generally responding in nonautomatic ways. The FRM generates responses by manipulating information and, to function effectively, its data input must be restricted to task-relevant information. The properties of consciousness correspond to the various input requirements of the FRM; and when important information is missing from consciousness, functions of the FRM are adversely affected; both of which indicate th...

Response and place memory systems have long been considered independent, encoding information in parallel, and involving the striatum and hippocampus, respectively. Most experimental studies supporting this view used simple, repetitive tasks, with unrestrained access to spatial cues. They did not give animals an opportunity to correct a response strategy by shifting to a place one, which would demonstrate dynamic, adaptive interactions between both memory systems in the navigation correction process. In a first experiment, rats were trained in the double-H maze for different durations (1, 6, or 14 days; 4 trials/day) to acquire a repetitive task in darkness (forcing a response memory-based strategy) or normal light (placing response and place memory systems in balance), or to acquire a place memory. All rats were given a misleading shifted-start probe trial 24-hr post-training to test both their strategy and their ability to correct their navigation directly or in response to negative feedback. Additional analyses focused on the dorsal striatum and the dorsal hippocampus using c-Fos gene expression imaging and, in a second experiment, reversible muscimol inactivation. The results indicate that, depending on training protocol and duration, the striatum, which was unexpectedly the first to come into play in the dual strategy task, and the hippocampus are both required when rats have to correct their navigation after having acquired a repetitive task in a cued environment. Partly contradicting the model established by Packard and McGaugh (1996, Neurobiology of Learning and Memory, vol 65), these data point to memory systems that interact in more complex ways than considered so far. To some extent, they also challenge the notion of hippocampus-independent response memory and striatum-independent place memory systems.

We report the results of a pre-registered, cluster randomized controlled trial of a mathematics learning intervention known as interleaved practice. Whereas most mathematics assignments consist of a block of problems devoted to the same skill or concept, an interleaved assignment is arranged so that no two consecutive problems require the same strategy. Previous smallscale studies found that practice assignments with a greater proportion of interleaved practice produced higher test scores. In the present study, we assessed the efficacy and feasibility of interleaved practice in a naturalistic setting with a large, diverse sample. Each of 54 seventhgrade mathematics classes periodically completed interleaved or blocked assignments over a period of four months, and then both groups completed an interleaved review assignment. One month later, students took an unannounced test, and the interleaved group outscored the blocked group, 61% vs. 38%, d = 0.83. Teachers were able to implement the intervention without training, and they later expressed support for interleaved practice in an anonymous survey they completed before they knew the results of the study. Although important caveats remain, the results suggest that interleaved mathematics practice is effective and feasible. Every school day, many millions of mathematics students complete a set of practice problems that can be solved with the same strategy, such as adding fractions by finding a common denominator. In an alternative approach known as interleaved practice, practice problems are arranged so that no two consecutive problems can be solved by the same strategy, and this approach forces students to choose an appropriate strategy for each problem on the basis of the problem itself. We conducted a large randomized classroom study and found that a greater emphasis on interleaved practice dramatically improved test scores.

Rats have a natural tendency to spend more time exploring novel objects than familiar objects, and this preference can be used as an index of object recognition. Rats also show an exploratory preference for objects in locations where they have not previously encountered objects (an index of place memory) and for familiar objects in contexts different from those in which the objects were originally encountered (an index of context memory). In this experiment, rats with cytotoxic lesions of the hippocampal formation were tested on all three versions of the novelty-preference paradigm, with a 5-min retention interval between the familiarization and test phases. Rats with sham lesions displayed a novelty preference on all three trial types, whereas the rats with hippocampal lesions displayed a novelty preference on Object trials but did not discriminate between the objects on Place trials or Context trials. The findings indicate that hippocampal damage impairs memory for contextual or s...

Cyclic AMP pathway plays an essential role in formation of long-term memory (LTM). In some species, the nitric oxide (NO)-cyclic GMP pathway has been found to act in parallel and complementary to the cAMP pathway for LTM formation. Here we describe a new role of the NO-cGMP pathway, namely, stimulation of the cAMP pathway to induce LTM. We have studied the signaling cascade underlying LTM formation by systematically coinjecting various “LTM-inducing” and “LTM-blocking” drugs in crickets. Multiple-trial olfactory conditioning led to LTM that lasted for several days, while memory induced by single-trial conditioning decayed away within several hours. Injection of inhibitors of the enzyme forming NO, cGMP, or cAMP into the hemolymph prior to multiple-trial conditioning blocked LTM, whereas injection of an NO donor, cGMP analog, or cAMP analog prior to single-trial conditioning induced LTM. Induction of LTM by injection of an NO donor or cGMP analog paired with single-trial conditioning...

On six days rats were exposed to each of two contexts. They received an electric shock in one context and nothing in the other. Rats were tested later in each environment without shock. The rats froze and defecated more often in the shock-paired environment; they also exhibited a significantly larger elevation in rectal temperature in that environment. The rats discriminated between each context, and we suggest that the elevation in temperature is the consequence of associative learning. Thus, body temperature can be used as a conditional response measure in Pavlovian fear conditioning experiments that use footshock as the unconditional stimulus.

The availability of potent synthetic agonists for cannabinoid receptors has facilitated our understanding of cannabinoid actions on synaptic transmission in the central nervous system. Moreover, the ability of these compounds to inhibit neurotransmitter release at many central synapses is thought to underlie most of the behavioral effects of cannabinoid agonists. However, despite the widespread use and misuse of marijuana, and recognition of its potential adverse psychological effects in humans, comparatively few studies have examined the actions of its primary psychoactive constituent, D-tetrahydrocannabinol (THC), at well-defined synaptic pathways. Here we examine the recent literature describing the effects of acute and repeated THC exposure on synaptic function in several brain regions and explore the importance of these neurobiological actions of THC in drug addiction.