Search

We tested the validity of two alternative accounts of the Attentional Boost Effect (ABE) - the finding that words associated with to-be-responded targets are recognized better than words associated with to-be-ignored distractors. The distinctiveness hypothesis assumes that, during recognition, participants probe their memories for distinctive information confirming that a word was studied (e.g., "I remember having pressed the spacebar, so I must have studied the word"). This strategy cannot be used in a between-subjects condition in which participants cannot appreciate the differences between target - and distractor-paired words. In agreement, Experiments 1A and 1B found that the ABE was significant in a within-subjects design, whereas it was eliminated in a between-subjects design. On the other hand, the performance anticipation hypothesis assumes that, during the study phase, participants anticipate the need of responding to a subset of target-paired words: this would create a persistent performance anticipation that would prevent them from effectively encoding distractor-paired words. In contrast with this account, we found that, when blocks of five distractor trials were regularly alternated with blocks of five target trials in Experiment 2, recognition accuracy decreased linearly in both conditions. Overall, these results suggest that distinctiveness, but not performance anticipation, might underlie the ABE.

Traumatic brain injury (TBI) represents one of the most common worldwide causes of death and disability. Clinical and animal model studies have evidenced that TBI is characterized by the loss of both gray and white matter, resulting in brain atrophy and in a decrease in neurological function. Nowadays, no effective treatments to counteract TBI-induced neurological damage are available. Due to its complex and multifactorial pathophysiology (neuro-inflammation, cytotoxicity and astroglial scar formation), cell regeneration and survival in injured brain areas are strongly hampered. Recently, it has been proposed that adult neurogenesis may represent a new approach to counteract the post-traumatic neurodegeneration. In our laboratory, we have recently shown that physical exercise induces the long-lasting enhancement of subventricular (SVZ) adult neurogenesis in a p21 (negative regulator of neural progenitor proliferation)-null mice model, with a concomitant improvement of olfactory behavioral paradigms that are strictly dependent on SVZ neurogenesis. On the basis of this evidence, we have investigated the effect of running on SVZ neurogenesis and neurorepair processes in p21 knock-out mice that were subject to TBI at the end of a 12-day session of running. Our data indicate that runner p21 ko mice show an improvement in numerous post-trauma neuro-regenerative processes, including the following: (i) an increase in neuroblasts in the SVZ; (ii) an increase in the migration stream of new neurons from the SVZ to the damaged cortical region; (iii) an enhancement of new differentiating neurons in the peri-lesioned area; (iv) an improvement in functional recovery at various times following TBI. All together, these results suggest that a running-dependent increase in subventricular neural stem cells could represent a promising tool to improve the endogenous neuro-regenerative responses following brain trauma.

In the Attentional Boost Effect (ABE), words or images encoded with to-be-detected target squares are later recognized better than words or images encoded with to-be-ignored distractor squares. The present study sought to determine whether the ABE enhanced the encoding of the item-specific and relational properties of the studied words by using the multiple recall paradigm. Previous evidence indicates that manipulations fostering item-specific encoding increased the number of item gains, whereas manipulations fostering relational encoding decreased item losses. Across three experiments, participants were presented with lists of semantically related or unrelated words paired with target (red) or distractor (green) squares, under the instructions to remember all the words and press the spacebar when the square was red. Immediately after the study phase, they were involved in four consecutive recall attempts. In all cases, the classical ABE was replicated, in that participants recalled more target- than distractor-paired words. Most importantly, the analyses converged in showing that item gains were significantly greater for target- than for distractor-paired words when participants studied lists of related words (but not when they studied unrelated lists); in contrast, item losses did not differ between the two types of words, irrespective of the nature of the studied list. Taken together, these data suggest that the ABE enhanced the encoding of item-specific information but had no effect on the encoding of relational information. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

In the attentional boost effect (ABE), words or images encoded with to-be-responded targets are later recalled better than words or images encoded with to-be-ignored distractors. The ABE has been repeatedly demonstrated to improve item memory, whereas evidence concerning contextual memory is mixed, with studies showing both significant and null results. The present three experiments investigated whether the ABE could enhance contextual memory when using a recognition task that allowed participants to reinstate the original study context, by simultaneously manipulating the nature of the instructions provided at encoding. Participants studied a sequence of colored words paired with target (gray circles) or distractor (gray squares) stimuli, under the instructions to remember either the words and their colors (Exps. 1-2) or only the words (Exp. 3) and simultaneously press the space bar whenever a gray circle appeared on the screen. Then, after a brief interval, they were administered a modified recognition task involving two successive stages. First, participants were presented with two different words and had to decide which word was originally encoded; second, they were presented with five colored versions of the (correct) old words and had to remember the color in which they were studied. Results converged in showing that the ABE enhanced contextual memory, although the effect was more robust with intentional encoding instructions., (© 2022. The Psychonomic Society, Inc.)

Neurogranin (Ng) is a brain-specific postsynaptic protein, whose role in modulating Ca 2+ /calmodulin signaling in glutamatergic neurons has been linked to enhancement in synaptic plasticity and cognitive functions. Accordingly, Ng knock-out (Ng-ko) mice display hippocampal-dependent learning and memory impairments associated with a deficit in long-term potentiation induction. In the adult olfactory bulb (OB), Ng is expressed by a large population of GABAergic granule cells (GCs) that are continuously generated during adult life, undergo high synaptic remodeling in response to the sensory context, and play a key role in odor processing. However, the possible implication of Ng in OB plasticity and function is yet to be investigated. Here, we show that Ng expression in the OB is associated with the mature state of adult-born GCs, where its active-phosphorylated form is concentrated at post-synaptic sites. Constitutive loss of Ng in Ng-ko mice resulted in defective spine density in adult-born GCs, while their survival remained unaltered. Moreover, Ng-ko mice show an impaired odor-reward associative memory coupled with reduced expression of the activity-dependent transcription factor Zif268 in olfactory GCs. Overall, our data support a role for Ng in the molecular mechanisms underlying GC plasticity and the formation of olfactory associative memory.

Previous studies indicate that pregnancy is associated with a mild impairment in verbal recall tasks, but the relative roles of item-specific and relational encoding processes have not been fully elucidated. The present study was specifically aimed at determining whether pregnancy had a differential impact on the use of these 2 types of encoding processes. The performance of pregnant, postpartum, and control women was assessed in the category-cued recall (Experiment 1: explicit memory) and category exemplar generation (Experiment 2: implicit memory) tasks, by simultaneously varying the number of exemplars presented during the study phase (1 exemplar for small categories, 6 exemplars for large categories). Control women showed the expected crossed double dissociation: Performance in category-cued recall was better for small than for large categories (confirming that this task relied on the use of item-specific encoding processes), whereas repetition priming in category exemplar generation was higher for large than for small categories (confirming that this task relied on the use of relational encoding processes). For pregnant and postpartum women, no significant differences between small and large categories were detected in the category-cued recall task; furthermore, in the category exemplar generation task, these 2 groups exhibited greater priming for small category exemplars. Overall, our data suggest that pregnancy might involve complex changes in the use of item-specific and relational encoding processes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

In the Attentional Boost Effect (ABE), images or words encoded with unrelated to-be-responded targets are later remembered better than images or words encoded with to-be-ignored distractors. In the realm of short-term memory, the ABE has been previously shown to enhance the short-term recognition of single-feature stimuli. The present study replicated this finding and extended it to a condition requiring the encoding and retention of colour-shape associations. Across four experiments, participants studied arrays of four coloured squares (the colour-only condition), four gray shapes (the shape-only condition) or four coloured shapes (the binding condition), paired with either a target letter (to which participants had to respond by pressing the spacebar) or a distractor letter (for which no response was required). After a short delay, they were presented with a probe array and asked to decide whether it matched or not the encoded array. Results showed that, in all conditions, the recognition of target-paired arrays was significantly better than the recognition of distractor-paired arrays. These findings suggest that the ABE can enhance feature binding.

Remembering places in which emotional events occur is essential for individual's survival. However, the mechanisms through which emotions modulate information processing in working memory, especially in the visuo-spatial domain, is little understood and controversial. The present research was aimed at investigating the effect of incidentally learned emotional stimuli on visuo-spatial working memory (VSWM) performance by using a modified version of the object-location task. Eight black rectangles appeared simultaneously on a computer screen; this was immediately followed by the sequential presentation of eight pictures (selected from IAPS) superimposed onto each rectangle. Pictures were selected considering the two main dimensions of emotions: valence and arousal . Immediately after presentation, participants had to relocate the rectangles in the original position as accurately as possible. In the first experiment arousal and valence were manipulated either as between-subject (Experiment 1A) or as within-subject factors (Experiment 1B and 1C). Results showed that negative pictures enhanced memory for object location only when they were presented with neutral ones within the same encoding trial. This enhancing effect of emotion on memory for object location was replicated also with positive pictures. In Experiment 2 the arousal level of negative pictures was manipulated between-subjects (high vs. low) while maintaining valence as a within-subject factor (negative vs. neutral). Objects associated with negative pictures were better relocated, independently of arousal. In Experiment 3 the role of emotional valence was further ascertained by manipulating valence as a within-subject factor (neutral vs. negative in Experiment 3A; neutral vs. positive in Experiment 3B) and maintaining similar levels of arousal among pictures. A significant effect of valence on memory for location was observed in both experiments. Finally, in Experiment 4, when positive and negative pictures were encoded in the same trial, no significant effect of valence on memory for object location was observed. Taken together results suggest that emotions enhance spatial memory performance when neutral and emotional stimuli compete with one another for access into the working memory system. In this competitive mechanism, an interplay between valence and arousal seems to be at work., (Copyright © 2019 Costanzi, Cianfanelli, Saraulli, Lasaponara, Doricchi, Cestari and Rossi-Arnaud.)

In the subventricular zone (SVZ) of the adult brain, the neural stem cells (NSCs) ensure a continuous supply of new neurons to the olfactory bulb (OB), playing a key role in its plasticity and olfactory-related behavior. The activation and expansion of NSCs within the SVZ are finely regulated by environmental and intrinsic factors. Running represents one of the most powerful neurogenic stimuli, although is ineffective in enhancing SVZ neurogenesis. The cell cycle inhibitor p21 is an intrinsic inhibitor of NSCs' expansion through the maintenance of their quiescence and the restrain of neural progenitor proliferation. In this work, we decided to test whether running unveils the intrinsic neurogenic potential of p21-lacking NSCs. To test this hypothesis, we examined the effect of three different paradigms of voluntary running (5, 12, and 21 days) on SVZ neurogenesis of p21 knockout (KO) male mice at two different stages of development, 2 and 12 months of age. In vivo and in vitro data clearly demonstrate that physical activity is consistent with the activation and expansion of NSCs and with the enhancement of SVZ neurogenesis in p21 KO mice. We also found that 12 days of running contribute to the increase in the number of new neurons functionally active within the OB, which associates with an improvement in olfactory performance strictly dependent on adult SVZ neurogenesis, i.e., the odor detection threshold and short-term olfactory memory. These data suggest that in the adult SVZ of p21 KO mice, NSCs retain a high neurogenic potential, triggered by physical activity, with long-term consequences in olfactory-related behavior.

The distinction between identification and production processes suggests that implicit memory should require more attention resources when there is a competition between alternative solutions during the test phase. The present two experiments assessed this hypothesis by examining the effects of divided attention (DA) at encoding on the high- and low-response-competition versions of perceptual identification (Experiment 1) and lexical decision (Experiment 2). In both experiments, words presented in the high-response-competition condition had many orthographic neighbours and at least one higher-frequency neighbour, whereas words presented in the low-response-competition condition had few orthographic neighbours and no higher-frequency neighbour. Consistent with the predictions of the identification/production distinction, Experiment 1 showed that DA reduced repetition priming in the high-, but not in the low-response-competition version of perceptual identification; in contrast, DA had comparable effects in the two versions of lexical decision (Experiments 2). These findings provide the first experimental evidence in support of the hypothesis that perceptual identification, a task nominally based on identification processes, might involve a substantive production component.

The present study examined predictions of the early-phase-elevated-attention hypothesis of the attentional boost effect (ABE), which suggests that transient increases in attention at encoding, as instantiated in the ABE paradigm, should enhance the recognition of neutral and positive items (whose encoding is mostly based on controlled processes), while having small or null effects on the recognition of negative items (whose encoding is primarily based on automatic processes). Participants were presented a sequence of negative, neutral and positive stimuli (pictures in Experiment 1, words in Experiment 2) associated to target (red) squares, distractor (green) squares or no squares (baseline condition). They were told to attend to the pictures/words and simultaneously press the spacebar of the computer when a red square appeared. In a later recognition task, stimuli associated to target squares were recognised better than stimuli associated to distractor squares, replicating the standard ABE. More importantly, we also found that: (a) the memory enhancement following target detection occurred with all types of stimuli (neutral, negative and positive) and (b) the advantage of negative stimuli over neutral stimuli was intact in the DA condition. These findings suggest that the encoding of negative stimuli depends on both controlled (attention-dependent) and automatic (attention-independent) processes.

Adult neurogenesis occurs throughout life in the dentate gyrus (DG) and the subventricular zone (SVZ), where glia-like stem cells generate new neurons. Voluntary running is a powerful neurogenic stimulus triggering the proliferation of progenitor cells in the DG but, apparently, not in the SVZ. The antiproliferative gene Btg1 maintains the quiescence of DG and SVZ stem cells. Its ablation causes intense proliferation of DG and SVZ stem/progenitor cells in young mice, followed, during adulthood, by progressive decrease of the proliferative capacity. We have previously observed that running can rescue the deficit of DG Btg1-null neurogenesis. Here, we show that in adult Btg1-null SVZ stem and neuroblast cells, the reduction of proliferation is associated with a longer cell cycle and a more frequent entry into quiescence. Notably, running increases proliferation in Btg1-null SVZ stem cells highly above the levels of sedentary wild-type mice and restores normal values of cell cycle length and quiescence in stem and neuroblast cells, without affecting wild-type cells. Btg1-null SVZ neuroblasts show also increased migration throughout the rostral migratory stream and a deficiency of differentiated neurons in the olfactory bulb, possibly a consequence of premature exit from the cycle; running, however, normalizes migration and differentiation, increasing newborn neurons recruited to the olfactory circuitry. Furthermore, running increases the self-renewal of Btg1-null SVZ-derived neurospheres and, remarkably, in aged Btg1-null mice almost doubles the proliferating SVZ stem cells. Altogether, this reveals that SVZ stem cells are endowed with a hidden supply of self-renewal capacity, coupled to cell cycle acceleration and emerging after ablation of the quiescence-maintaining Btg1 gene and following exercise.

Cell proliferation and differentiation are interdependent processes. Here, we have asked to what extent the two processes of neural progenitor cell amplification and differentiation are functionally separated. Thus, we analyzed whether it is possible to rescue a defect of terminal differentiation in progenitor cells of the dentate gyrus, where new neurons are generated throughout life, by inducing their proliferation and/or their differentiation with different stimuli appropriately timed. As a model we used the Tis21 knockout mouse, whose dentate gyrus neurons, as demonstrated by us and others, have an intrinsic defect of terminal differentiation. We first tested the effect of two proliferative as well as differentiative neurogenic stimuli, one pharmacological (fluoxetine), the other cognitive (the Morris water maze (MWM) training). Both effectively enhanced the number of new dentate gyrus neurons produced, and fluoxetine also reduced the S-phase length of Tis21 knockout dentate gyrus progenitor cells and increased the rate of differentiation of control cells, but neither factor enhanced the defective rate of differentiation. In contrast, the defect of terminal differentiation was fully rescued by in vivo infection of proliferating dentate gyrus progenitor cells with retroviruses either silencing Id3, an inhibitor of neural differentiation, or expressing NeuroD2, a proneural gene expressed in terminally differentiated dentate gyrus neurons. This is the first demonstration that NeuroD2 or the silencing of Id3 can activate the differentiation of dentate gyrus neurons, complementing a defect of differentiation. It also highlights how the rate of differentiation of dentate gyrus neurons is regulated genetically at several levels and that a neurogenic stimulus for amplification of neural stem/progenitor cells may not be sufficient in itself to modify this rate.

Background: The rapid lengthening of life expectancy has raised the problem of providing social programs to counteract the age-related cognitive decline in a growing number of older people. Physical activity stands among the most promising interventions aimed at brain wellbeing, because of its effective neuroprotective action and low social cost. The purpose of this review is to describe the neuroprotective role exerted by physical activity in different life stages. In particular, we focus on adult neurogenesis, a process which has proved being highly responsive to physical exercise and may represent a major factor of brain health over the lifespan., Methods: The most recent literature related to the subject has been reviewed. The text has been divided into three main sections, addressing the effects of physical exercise during childhood/ adolescence, adulthood and aging, respectively. For each one, the most relevant studies, carried out on both human participants and rodent models, have been described., Results: The data reviewed converge in indicating that physical activity exerts a positive effect on brain functioning throughout the lifespan. However, uncertainty remains about the magnitude of the effect and its biological underpinnings. Cellular and synaptic plasticity provided by adult neurogenesis are highly probable mediators, but the mechanism for their action has yet to be conclusively established., Conclusion: Despite alternative mechanisms of action are currently debated, age-appropriate physical activity programs may constitute a large-scale, relatively inexpensive and powerful approach to dampen the individual and social impact of age-related cognitive decline., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

It has been recently proposed that pregnant women would perform memory tasks by focusing more on item-specific processes and less on relational processing, compared to post-partum women (Mickes, Wixted, Shapiro & Scarff, ). The present cross-sectional study tested this hypothesis by directly manipulating the type of encoding employed in the study phase. Pregnant, post-partum and control women either rated the pleasantness of word meaning (which induced item-specific elaboration) or named the semantic category to which they belonged (which induced relational elaboration). Memory for the encoded words was later tested in free recall (which emphasizes relational processing) and in recognition (which emphasizes item-specific processing). In line with Mickes et al.'s () conclusions, pregnant women in the item-specific condition performed worse than post-partum women in the relational condition in free recall, but not in recognition. However, compared to the other two groups, pregnant women also exhibited lower recognition accuracy in the item-specific condition. Overall, these results confirm that pregnant women rely on relational encoding less than post-partum women, but additionally suggest that the former group might use item-specific processes less efficiently than post-partum and control women., (© 2016 Scandinavian Psychological Associations and John Wiley & Sons Ltd.)

Objective: Previous studies examining implicit memory in schizophrenia yielded inconsistent results. The present meta-analysis aimed at determining whether, compared to healthy controls, schizophrenic patients: (a) exhibited reduced priming in the whole set of studies; (b) were differentially impaired in conceptual/perceptual and production/identification tests; and (c) were less efficient in the use of semantic encoding processes., Method: A systematic search in PsycINFO and PubMed led to the selection of 22 critical studies (31 effect sizes), comparing repetition priming in 836 schizophrenic patients and 760 healthy controls. Moderators were assessed by classifying implicit tasks into the perceptual/conceptual and identification/production categories, and by distinguishing between perceptual and conceptual encoding instructions., Results: Overall, implicit memory was slightly, but significantly, impaired in schizophrenia (d=0.179). Patients exhibited reduced priming in conceptually-driven tasks (d=0.447), but intact priming in perceptually-driven tasks (d=0.080). No significant difference was observed between identification and production priming (d=0.064 vs. d=0.243). Finally, priming in schizophrenic patients was significantly lower than that of controls when the encoding task required the analysis of the conceptual properties of the stimuli (d=0.261)., Conclusion: Results suggest that schizophrenia is associated with a specific deficit in the use of conceptual processes, both at encoding and at retrieval. In contrast with theoretical expectations, high levels of response competition did not disproportionately impair the patients' performance., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Fear allows organisms to cope with dangerous situations and remembering these situations has an adaptive role preserving individuals from injury and death. However, recalling traumatic memories can induce re-experiencing the trauma, thus resulting in a maladaptive fear. A failure to properly regulate fear responses has been associated with anxiety disorders, like Posttraumatic Stress Disorder (PTSD). Thus, re-establishing the capability to regulate fear has an important role for its adaptive and clinical relevance. Strategies aimed at erasing fear memories have been proposed, although there are limits about their efficiency in treating anxiety disorders. To re-establish fear regulation, here we propose a new approach, based on the re-evaluation of the aversive value of traumatic experience. Mice were submitted to a contextual-fear-conditioning paradigm in which a neutral context was paired with an intense electric footshock. Three weeks after acquisition, conditioned mice were treated with a less intense footshock (pain threshold). The effectiveness of this procedure in reducing fear expression was assessed in terms of behavioral outcomes related to PTSD (e.g., hyper-reactivity to a neutral tone, anxiety levels in a plus maze task, social avoidance, and learning deficits in a spatial water maze) and of amygdala activity by evaluating c-fos expression. Furthermore, a possible role of lateral orbitofrontal cortex (lOFC) in mediating the behavioral effects induced by the re-evaluation procedure was investigated. We observed that this treatment: (i) significantly mitigates the abnormal behavioral outcomes induced by trauma; (ii) persistently attenuates fear expression without erasing contextual memory; (iii) prevents fear reinstatement; (iv) reduces amygdala activity; and (v) requires an intact lOFC to be effective. These results suggest that an effective strategy to treat pathological anxiety should address cognitive re-evaluation of the traumatic experience mediated by lOFC.

The present study reports 2 experiments examining the Attentional Boost Effect (ABE) in schizophrenic patients and matched healthy controls, using visual and verbal materials. The ABE refers to the surprising finding that, in a divided attention condition, images and words encoded with targets are remembered better than images and words encoded with distractors. Unlike controls (who showed the typical ABE), schizophrenic patients reported no memory advantage for stimuli presented together with targets in the divided attention condition. On the other hand, the interference effect on the recognition of stimuli presented with distractors was not exacerbated in patients (as compared with controls). In line with the dual-task interaction model proposed by Swallow and Jiang (2013), the absence of a significant facilitation indicates that schizophrenic patients have a deficit in the process of attentional enhancement triggered by target detection. A number of neural mechanisms potentially underlying this impairment are discussed, as well as implications for the characterization of the attentional deficits involved in schizophrenia., ((c) 2014 APA, all rights reserved.)

Physical exercise increases the generation of new neurons in adult neurogenesis. However, only few studies have investigated the beneficial effects of physical exercise in paradigms of impaired neurogenesis. Here, we demonstrate that running fully reverses the deficient adult neurogenesis within the hippocampus and subventricular zone of the lateral ventricle, observed in mice lacking the antiproliferative gene Btg1. We also evaluated for the first time how running influences the cell cycle kinetics of stem and precursor subpopulations of wild-type and Btg1-null mice, using a new method to determine the cell cycle length. Our data show that in wild-type mice running leads to a cell cycle shortening only of NeuroD1-positive progenitor cells. In contrast, in Btg1-null mice, physical exercise fully reactivates the defective hippocampal neurogenesis, by shortening the S-phase length and the overall cell cycle duration of both neural stem (glial fibrillary acidic protein(+) and Sox2(+)) and progenitor (NeuroD1(+)) cells. These events are sufficient and necessary to reactivate the hyperproliferation observed in Btg1-null early-postnatal mice and to expand the pool of adult neural stem and progenitor cells. Such a sustained increase of cell proliferation in Btg1-null mice after running provides a long-lasting increment of proliferation, differentiation, and production of newborn neurons, which rescues the impaired pattern separation previously identified in Btg1-null mice. This study shows that running positively affects the cell cycle kinetics of specific subpopulations of newly generated neurons and suggests that the plasticity of neural stem cells without cell cycle inhibitory control is reactivated by running, with implications for the long-term modulation of neurogenesis., (© 2014 AlphaMed Press.)

The highly conserved mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling cascade is involved in several intracellular processes ranging from cell differentiation to proliferation, as well as in synaptic plasticity. In the last two decades, the role of MAPK/ERK in long-term memory formation in mammals, particularly in fear-related memories, has been extensively investigated. In this review we describe knowledge advancement on the role of MAPK/ERK in orchestrating the intracellular processes that lead to the consolidation, reconsolidation and extinction of fear memories. In doing so, we report studies in which the specific role of MAP/ERK in switching from memory formation to memory erasure has been suggested. The possibility to target MAPK/ERK in developing and/or refining pharmacological approaches to treat psychiatric disorders in which fear regulation is defective has also been envisaged., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Bone morphogenic proteins (BMPs) and the Notch pathway regulate quiescence and self-renewal of stem cells of the subventricular zone (SVZ), an adult neurogenic niche. Here we analyze the role at the intersection of these pathways of Tis21 (Btg2/PC3), a gene regulating proliferation and differentiation of adult SVZ stem and progenitor cells. In Tis21-null SVZ and cultured neurospheres, we observed a strong decrease in the expression of BMP4 and its effectors Smad1/8, while the Notch anti-neural mediators Hes1/5 and the basic helix-loop-helix (bHLH) inhibitors Id1-3 increased. Consistently, expression of the proneural bHLH gene NeuroD1 decreased. Moreover, cyclins D1/2, A2, and E were strongly up-regulated. Thus, in the SVZ Tis21 activates the BMP pathway and inhibits the Notch pathway and the cell cycle. Correspondingly, the Tis21-null SVZ stem cells greatly increased; nonetheless, the proliferating neuroblasts diminished, whereas the post-mitotic neuroblasts paradoxically accumulated in SVZ, failing to migrate along the rostral migratory stream to the olfactory bulb. The ability, however, of neuroblasts to migrate from SVZ explants was not affected, suggesting that Tis21-null neuroblasts do not migrate to the olfactory bulb because of a defect in terminal differentiation. Notably, BMP4 addition or Id3 silencing rescued the defective differentiation observed in Tis21-null neurospheres, indicating that they mediate the Tis21 pro-differentiative action. The reduced number of granule neurons in the Tis21-null olfactory bulb led to a defect in olfactory detection threshold, without effect on olfactory memory, also suggesting that within olfactory circuits new granule neurons play a primary role in odor sensitivity rather than in memory.

The present study investigated the use of perceptual binding processes in schizophrenic (SC) patients and matched healthy controls, by examining their performance on the recall of symmetrical (vertical, horizontal and diagonal) and asymmetrical patterns varying in length between 2 and 9 items. The results showed that, although SC patients were less accurate than controls in all conditions, both groups recalled symmetrical patterns better than asymmetrical ones. The impairment of SC patients was magnified with supra-span symmetrical arrays, and they were more likely to reproduce symmetrical patterns as asymmetrical, particularly at medium and high length levels. Hierarchical regression analyses further indicated that the between-group differences in the recall of supra-span vertical and horizontal arrays, which require a greater involvement of visual pattern processes, remained significant after removing the variance associated with performance on asymmetrical patterns, which primarily reflects intrafigural spatial processes. It is proposed that schizophrenia may be associated with a specific deficit in the formation and retrieval of the global visual images of studied patterns and in the use of the on-line information about the type of symmetry being tested to guide retrieval processes., (© 2013 Elsevier B.V. All rights reserved.)

Different pathological tau species are involved in memory loss in Alzheimer's disease, the most common cause of dementia among older people. However, little is known about how tau pathology directly affects adult hippocampal neurogenesis, a unique form of structural plasticity implicated in hippocampus-dependent spatial learning and mood-related behavior. To this aim, we generated a transgenic mouse model conditionally expressing a pathological tau fragment (26-230 aa of the longest human tau isoform, or N-tau) in nestin-positive stem/progenitor cells. We found that N-tau reduced the proliferation of progenitor cells in the adult dentate gyrus, reduced cell survival and increased cell death by a caspase-3-independent mechanism, and recruited microglia. Although the number of terminally differentiated neurons was reduced, these showed an increased dendritic arborization and spine density. This resulted in an increase of anxiety-related behavior and an impairment of episodic-like memory, whereas less complex forms of spatial learning remained unaltered. Understanding how pathological tau species directly affect neurogenesis is important for developing potential therapeutic strategies to direct neurogenic instructive cues for hippocampal function repair., (Copyright © 2013 Elsevier Inc. All rights reserved.)

The analysis of the interaction between repetition priming and age of acquisition may be used to shed further light on the question of which stages of elaboration are affected by this psycholinguistic variable. In the present study we applied this method in the context of two versions of a lexical decision task that differed in the type of non-words employed at test. When the non-words were illegal and unpronounceable, repetition priming was primarily based on the analysis of orthographic information, while phonological processes were additionally recruited only when using legal pronounceable non-words. The results showed a significant interaction between repetition priming and age of acquisition in both conditions, with priming being greater for late- than for early-acquired words. These findings support a multiple-loci account, indicating that age of acquisition influences implicit memory by facilitating the retrieval of both the orthographic and the phonological representations of studied words.

Btg1 belongs to a family of cell cycle inhibitory genes. We observed that Btg1 is highly expressed in adult neurogenic niches, i.e., the dentate gyrus and subventricular zone (SVZ). Thus, we generated Btg1 knockout mice to analyze the role of Btg1 in the process of generation of adult new neurons. Ablation of Btg1 causes a transient increase of the proliferating dentate gyrus stem and progenitor cells at post-natal day 7; however, at 2 months of age the number of these proliferating cells, as well as of mature neurons, greatly decreases compared to wild-type controls. Remarkably, adult dentate gyrus stem and progenitor cells of Btg1-null mice exit the cell cycle after completing the S phase, express p53 and p21 at high levels and undergo apoptosis within 5 days. In the SVZ of adult (two-month-old) Btg1-null mice we observed an equivalent decrease, associated to apoptosis, of stem cells, neuroblasts, and neurons; furthermore, neurospheres derived from SVZ stem cells showed an age-dependent decrease of the self-renewal and expansion capacity. We conclude that ablation of Btg1 reduces the pool of dividing adult stem and progenitor cells in the dentate gyrus and SVZ by decreasing their proliferative capacity and inducing apoptosis, probably reflecting impairment of the control of the cell cycle transition from G1 to S phase. As a result, the ability of Btg1-null mice to discriminate among overlapping contextual memories was affected. Btg1 appears, therefore, to be required for maintaining adult stem and progenitor cells quiescence and self-renewal.

The psychological correlates of enuresis are receiving growing attention, coherently with a multi-factorial approach to this problem, but to date the empirical findings are still inconsistent and incomplete. The aim of this study is to contribute to the understanding of the socio-affective functioning of enuretic children by exploring four central dimensions: attachment, self-esteem, self-control, and temperament. Twenty-two enuretic children with their mothers were enrolled in the study and matched, based on gender and age, to a control group of continent healthy children. Measures were collected through mothers' reports and individual administrations to all children. Controlling for socio-demographic variables, we found a significantly lower incidence of secure attachment, lower self-esteem, and higher rates of behavioral problems among the enuretic group, compared with the control group. No differences in the temperamental dimensions were found. These preliminary findings support the view of enuresis as a bio-behavioral problem and, from a practical standpoint, underline the urgency for physicians not to underestimate this disturbance, but, indeed, to treat the problem through medical strategies and to devote attention to the psychological difficulties of these patients.

Long-lasting memories of adverse experiences are essential for individuals' survival but are also involved, in the form of recurrent recollections of the traumatic experience, in the aetiology of anxiety diseases (e.g., post-traumatic stress disorder [PTSD]). Extinction-based erasure of fear memories has long been pursued as a behavioral way to treat anxiety disorders; yet, such a procedure turns out to be transient, context-dependent, and ineffective unless it is applied immediately after trauma. Recent evidence indicates that, in both rats and humans, extinction training can prevent the return of fear if administered within the reconsolidation window, when memories become temporarily labile and susceptible of being updated. Here, we show that the reconsolidation-extinction procedure fails to prevent the spontaneous recovery of a remote contextual fear memory in a mouse model of PTSD, as well as the long-lasting behavioral abnormalities induced by traumatic experience on anxiety and in both social and cognitive domains (i.e., social withdrawal and spatial learning deficits). Such a failure appears to be related to the ineffectiveness of the reconsolidation-extinction procedure in targeting the pathogenic process of fear sensitization, a nonassociative component of traumatic memory that causes animals to react aberrantly to harmless stimuli. This indicates fear sensitization as a major target for treatments aimed at mitigating anxiety and the behavioral outcomes of traumatic experiences.

RNA-Induced Silencing Complex (RISC) mediates post-transcriptional control of gene expression and contains Argonaute 2 (AGO2) protein as a central effector of cleavage or inhibition of mRNA translation. In the brain, the RISC pathway is involved in neuronal functions, such as synaptic development and local protein synthesis, which are potentially critical for memory. In this study, we examined the role of RISC in memory formation in rodents, by silencing AGO2 expression in dorsal hippocampus of C57BL/6 mice and submitting animals to hippocampus-related tasks. One week after surgery, AGO2 downregulation impaired both short-term and long-term contextual fear memories. Conversely, no long-lasting effects were observed three weeks after surgery, when AGO2 levels were re-established. These results show that altered RISC activity severely affects learning and memory processes in rodents.

Neurogenesis in the dentate gyrus of the adult hippocampus has been implicated in neural plasticity and memory, but the molecular mechanisms controlling the proliferation and differentiation of newborn neurons and their integration into the synaptic circuitry are still largely unknown. To investigate this issue, we have analyzed the adult hippocampal neurogenesis in a PC3/Tis21-null mouse model. PC3/Tis21 is a transcriptional co-factor endowed with antiproliferative and prodifferentiative properties; indeed, its upregulation in neural progenitors has been shown to induce exit from cell cycle and differentiation. We demonstrate here that the deletion of PC3/Tis21 causes an increased proliferation of progenitor cells in the adult dentate gyrus and an arrest of their terminal differentiation. In fact, in the PC3/Tis21-null hippocampus postmitotic undifferentiated neurons accumulated, while the number of terminally differentiated neurons decreased of 40%. As a result, PC3/Tis21-null mice displayed a deficit of contextual memory. Notably, we observed that PC3/Tis21 can associate to the promoter of Id3, an inhibitor of proneural gene activity, and negatively regulates its expression, indicating that PC3/Tis21 acts upstream of Id3. Our results identify PC3/Tis21 as a gene required in the control of proliferation and terminal differentiation of newborn neurons during adult hippocampal neurogenesis and suggest its involvement in the formation of contextual memories.

Adult neurogenesis in the dentate gyrus plays a critical role in hippocampus-dependent spatial learning. It remains unknown, however, how new neurons become functionally integrated into spatial circuits and contribute to hippocampus-mediated forms of learning and memory. To investigate these issues, we used a mouse model in which the differentiation of adult-generated dentate gyrus neurons can be anticipated by conditionally expressing the pro-differentiative gene PC3 (Tis21/BTG2) in nestin-positive progenitor cells. In contrast to previous studies that affected the number of newly generated neurons, this strategy selectively changes their timing of differentiation. New, adult-generated dentate gyrus progenitors, in which the PC3 transgene was expressed, showed accelerated differentiation and significantly reduced dendritic arborization and spine density. Functionally, this genetic manipulation specifically affected different hippocampus-dependent learning and memory tasks, including contextual fear conditioning, and selectively reduced synaptic plasticity in the dentate gyrus. Morphological and functional analyses of hippocampal neurons at different stages of differentiation, following transgene activation within defined time-windows, revealed that the new, adult-generated neurons up to 3-4 weeks of age are required not only to acquire new spatial information but also to use previously consolidated memories. Thus, the correct unwinding of these key memory functions, which can be an expression of the ability of adult-generated neurons to link subsequent events in memory circuits, is critically dependent on the correct timing of the initial stages of neuron maturation and connection to existing circuits.