Orofacial pain models induce impairment in spatial learning and working memory in rodents: A systematic review and meta-analysis.

Orofacial pain is one of the most common causes of chronic pain leading to physical and cognitive disability. Several clinical and pre-clinical studies suggest that chronic pain results in cognitive impairment. However, there is a lack of meta-analyses examining the effects of orofacial pain models on behavioral learning and memory in rodents. Thus, this study aimed to evaluate whether orofacial pain models can impair learning and memory in rodents. The protocol was registered in PROSPERO (CRD42023355502). We used CAMARADES and SYRCLE to estimate the quality and the publication bias by using Egger's and Begg's test. Here, 21 studies were included in this systematic review and meta-analysis. We included 12 studies with trigeminal neuralgia models, 4 with migraine-like pain models, 4 with tooth nociception, and 1 with acute orofacial pain model. Spontaneous nociception and facial mechanical allodynia were observed in orofacial pain models. Regarding spatial learning we detected that latency to find the platform in the Morris water maze (MWM) was increased in orofacial pain models (related to facial mechanical allodynia or spontaneous nociception). Although the mean quality of the articles was high, we identify publication bias in the Begg's test for the time in the quadrant in the MWM. Our findings revealed that spontaneous nociception and facial mechanical allodynia in orofacial pain models contribute to the working memory and spatial learning dysfunction. Therefore, further studies are still needed to evaluate the influence of sex, age, social isolation, and environmental enrichment in orofacial pain-related learning and memory.

Acute glyphosate and aminomethylphosphonic acid (AMPA), its major metabolite, impaired spatial orientation, navigation, learning and/or memory in female rats.

Human exposure to glyphosate-based herbicides (GBH) has been associated with a range of toxicological effects involving the central nervous system (CNS) such as alterations in learning and memory. Nevertheless, the effects of aminomethylphosphonic acid (AMPA), the main metabolite of glyphosate, remain essentially obscure. Previous preclinical reports suggest that acute intoxication with AMPA and glyphosate exerts decrease on hippocampal acetylcholinesterase activity and produces more metabolomic alterations in the female brain over the male one. Therefore, this work explored the effects of acute AMPA and glyphosate on spatial learning, memory and navigation in female rats. Sprague Dawley rats received a single injection (i.p.) of: (i) vehicle; (ii) 10 or 100 mg/kg of AMPA; or (iii) 10 or 100 mg/kg of glyphosate; subsequently, the Barnes maze paradigm was performance. Animals from the control group decreased latency and the attempts to solve the Barnes maze; and increased the degree of orientation when compared first training sessions (S1) vs. the last one (S4; p < 0.05). In contrast, both 10 and 100 mg/kg of glyphosate and 100 mg/kg of AMPA prevented the decrease in latency and attempts; and the increase of orientation (p > 0.05; S1 vs. S4). Both treatments decreased the use of the spatial navigation strategy (p < 0.05). Besides, glyphosate at the higher dose but not AMPA impaired the spatial memory during the test. Our findings suggest that acute exposure to glyphosate and AMPA similarly affected spatial orientation, navigations, learning and/or memory.

Investigating Morphological Changes of the Hippocampus After Prolonged Aerobic Exercise in Mice: Neural Function and Learning Capabilities / Investigación de los Cambios Morfológicos del Hipocampo Después De un Ejercicio Aeróbico Prolongado en Ratones: Función Neuronal y Capacidades de Aprendizaje

SUMMARY: Both the academic and popular worlds have paid close attention to the link between exercise and cognitive performance. It is increasingly important to understand the numerous mechanisms by which exercise might influence cognitive abilities in view of the continuous societal issues caused by aging populations and the prevalence of disorders associated to cognitive decline. A rising amount of evidence showing a favorable association between physical activity and cognitive well-being serves as the foundation for the justification for studying the effects of exercise on cognitive function and learning ability. The study employed an 8-week treadmill based on exercise on male adults C57BL/6 mice. The exercise group were engaged in 5 sessions a week gradually increasing the intensity of the protocol by 5 % each week. The Mice cognitive assessments were done using Morris Water Maze and Novel Object Recognition tests. The long term-impact on learning ability were further assessed through immmohistochemistry and molecular analysis of the hippocampal and prefrontal cortex tissues of the animals' brain tissues. The findings showed improved spatial learning abilities, recognition memory, and heighted synaptic plasticity indicated by elevated synaptic makers. The study underscores the role of long-term aerobic exercise in augmenting cognitive performance. It not only contributes to the understanding of the interplay between neuroplasticity and cognitive benefits but also the growing body of research on the impact of exercise on cognitive function.

Tanto el mundo académico como el popular han prestado mucha atención al vínculo entre el ejercicio y el rendimiento cognitivo. Es cada vez más importante comprender los numerosos mecanismos por los cuales el ejercicio podría influir en las capacidades cognitivas en vista de los continuos problemas sociales causados por el envejecimiento de la población y la prevalencia de trastornos asociados al deterioro cognitivo. Una cantidad cada vez mayor de evidencia que muestra una asociación favorable entre la actividad física y el bienestar cognitivo sirve como base para justificar el estudio de los efectos del ejercicio sobre la función cognitiva y la capacidad de aprendizaje. El estudio se realizó en ratones machos adultos C57BL/6 utilizándose en los ejercicios una cinta rodante durante 8 semanas. El grupo de ejercicio realizó 5 sesiones por semana aumentando gradualmente la intensidad del protocolo en un 5 % cada semana. Las evaluaciones cognitivas de los ratones se realizaron utilizando las pruebas Morris Water Maze y Novel Object Recognition. El impacto a largo plazo en la capacidad de aprendizaje se evaluó mediante inmunohistoquímica y análisis molecular de los tejidos del hipocampo y la corteza prefrontal de los tejidos cerebrales de los animales. Los hallazgos mostraron mejoras en las habilidades de aprendizaje espacial, la memoria de reconocimiento y una mayor plasticidad sináptica indicada por unos creadores sinápticos elevados. El estudio subraya el papel del ejercicio aeróbico a largo plazo para aumentar el rendimiento cognitivo. No sólo contribuye a la comprensión de la interacción entre la neuroplasticidad y los beneficios cognitivos, sino también al creciente conjunto de investigaciones sobre el impacto del ejercicio en la función cognitiva.

The novel FAAH inhibitor, MCH1, reduces the infarction area in the motor cortex-related region but does not affect the sensorimotor function or memory and spatial learning in rats exposed to transient middle cerebral artery occlusion.

Macamides, amides of fatty acids first isolated from maca (Lepidium meyenii) are potentially responsible for the reduction of ischemic injury in the stroke animal model followed by maca extract administration. This deduction comes from its ability to inhibit the fatty acid amide hydrolase activity, an enzyme related to the endocannabinoid anandamide hydrolysis. However, no study about the effects of isolated macamides on in-vivo models has been published yet. Our objective was to evaluate the effect of a 10-day 30 mg/kg i.p. MCH1 administration, the macamide with the higher FAAH inhibition capability, on the neurological recovery and brain infarction area of Sprague-Dawley rats exposed to the transient middle cerebral artery occlusion (MCAO) model. Our results showed that the group receiving MCH1 for 10 days did not improve Garcia's neurological score compared to receiving the vehicle only. Likewise, the MCH1 group did not improve their sensorimotor dysfunction as indicated by the latency to detect and remove the tape from the contralateral forepaw in the adhesive removal test, and a similar number of errors with the contralateral forepaw in the foot fault test compared to the vehicle group at the 10th day. Evaluation of the spatial memory and learning using the Barnes test showed longer latency to reach the escape box in the Vehicle and MCH1 groups compared to the control group (no MCAO) only in the retrieval test, while no effect of MCAO procedure or MCH1 administration was observed in the reversal learning test. Despite the lack of behavioral effect of MCH1, analysis of the infarcted areas in the brain using the 2, 3, 5-Triphenyltetrazolium chloride (TTC) staining method in the seven consecutive coronal sections revealed that the infarcted area in the first (bregma + 4.2 mm) and fifth (bregma -3.8 mm) coronal sections of the MCAO + MCH1 group remained similar to the Control group. These results provide evidence that MCH1 can limit damage from ischemic stroke, although it is not reflected in neurological or sensorimotor behavior and spatial learning and memory.

Attention-deficit/hyperactivity disorder and inflammation: natural product-derived treatments-a review of the last ten years.

OBJECTIVE: Attention-deficit hyperactivity disorder (ADHD) is a psychiatric disorder characterized by symptoms of inattention, hyperactivity, and impulsivity. Stimulant medication is the main pharmacological treatment for ADHD. However, the traditional pharmacological treatments may have significant side effects; therefore, non-pharmacological approaches are needed. Thus, there has been growing interest in alternative herbal treatments. The aim of this review was to comprehensively assess the current evidence for plant-based treatment of ADHD in human and animal models, as well as their ability to modulate the inflammatory process. METHODS: This study was an integrative review of the current evidence for the plant-based treatment of ADHD. The research involved using literature available on PubMed and Scopus databases. FINDINGS: Spontaneously hypersensitive rats treated with baicalin exhibited significant reductions in locomotion, increased spatial learning skills, and increased levels of dopamine in the striatum. Supplementation with Sansonite improved memory and attention capacity. In human studies, Ginkgo biloba significantly improved the symptoms of inattention and reduced memory impairment. In studies conducted using Korean Red ginseng, Klamath, and Crocus sativus L., the patients showed significant improvements in symptoms of inattention and hyperactivity/impulsivity. Furthermore, we demonstrated that the identified plants modulate the inflammatory process through pro-inflammatory and anti-inflammatory cytokines, nitric oxide, Th cells, Toll-like receptor 4, and mitogen-activated protein kinases. CONCLUSION: All the studies included in this review focused on plants with demonstrated potential against inflammatory processes, positioning them as promising candidates for ADHD treatment, due to their potential to attenuate or even prevent neuroinflammatory mechanisms.

Effects of acute maternal stress induced by predator cues on spatial learning and memory of offspring in the subterranean rodent Ctenomys talarum.

One of the main selection pressures to which animals are exposed in nature is predation, which affects a wide variety of biological traits. When the mother experiences this stressor during pregnancy and/or lactation, behavioral and physiological responses may be triggered in the offspring as well. Thus, in order to broaden and deepen knowledge on the transgenerational effects of predation stress, we evaluated how maternal stress experienced during pregnancy and/or lactation affects the spatial abilities of progeny at the onset of adulthood in the subterranean rodent Ctenomys talarum. The results showed that, contrary to what was observed in other rodent species, maternal exposure to predator cues during pregnancy and lactation did not negatively affect the spatial abilities of the offspring, even registering some minor positive effects. Concomitantly, no effects of predatory cues on physiological parameters associated with stress were observed in the progeny. This difference in results between the present study and previous works on maternal stress highlights the importance of considering the species to be evaluated (strain, age and origin-wild or captive-) and the type of stressor used (artificial or natural, intensity of exposure) in the evaluation of the possible transgenerational effects of maternal stress.

Dyadic visual perceptual learning on orientation discrimination.

The belief that learning can be modulated by social context is mainly supported by high-level value-based learning studies. However, whether social context can even modulate low-level learning such as visual perceptual learning (VPL) is still unknown. Unlike traditional VPL studies in which participants were trained singly, here, we developed a novel dyadic VPL paradigm in which paired participants were trained with the same orientation discrimination task and could monitor each other's performance. We found that the social context (i.e., dyadic training) led to a greater behavioral performance improvement and a faster learning rate compared with the single training. Interestingly, the facilitating effects could be modulated by the performance difference between paired participants. Functional magnetic resonance imaging (fMRI) results showed that, compared with the single training, social cognition areas including bilateral parietal cortex and dorsolateral prefrontal cortex displayed a different activity pattern and enhanced functional connectivities to early visual cortex (EVC) during the dyadic training. Furthermore, the dyadic training resulted in more refined orientation representation in primary visual cortex (V1), which was closely associated with the greater behavioral performance improvement. Taken together, we demonstrate that the social context, learning with a partner, can remarkably augment the plasticity of low-level visual information process by means of reshaping the neural activities in EVC and social cognition areas, as well as their functional interplays.

Starting maternal exercise, unlike reducing the intensity of exercise during pregnancy, prevents memory deficits in female offspring subject to maternal deprivation.

Maternal deprivation (MD) leads to long-lasting memory deficits. Conversely, maternal exercise could potently modify the offspring's cellular machinery. Here, we tested whether starting to run or reducing the intensity of running during pregnancy can protect prepubertal female offspring against MD-induced memory deficits. Female rats were divided into different groups submitted or not to MD: one started to run before pregnancy and reduced the intensity during the pregnancy (PGE); another started to run at the beginning of pregnancy (GE); and, finally, a control group (CT) was not submitted to exercise. All the rats but those of the CT ran on a treadmill until the delivery day (PND 0). Subsequently, MD was performed from PND 1 to 10. We assessed object recognition (OR) and spatial memory (SM) of female offspring after weaning (PND22, pre-pubertal stage). MD caused OR memory deficit; GE female offspring did not present this deficit, but PGE did. Both PGE and GE alone enhanced offspring spatial learning, but their combination with MD impaired it. MD promoted hippocampal lipid peroxidation increase, which both PGE and GE prevented. Total antioxidant capacity in the hippocampus was higher in both MD-exercised groups compared to all others. Although the antioxidant effects of exercise were similar in both MD exercise groups, we observed better results in the memory tests in the GE group than in the PGE group. These results suggest that starting to exercise during pregnancy is better than reducing the exercise intensity during pregnancy to prevent MD-induced memory deficits in female offspring.

Chronic restraint stress alters rat behavior depending on sex and duration of stress.

Chronic restraint stress (CRS) can have different behavioral effects depending on variables associated with the stressor and the organism. This study aimed to verify the effect of the interaction between sex and duration of the CRS protocol in rats. Sprague-Dawley rats were divided by sex, intervention (CRS; control), and CRS duration (11 days; 22 days). Rats exposed to CRS showed better spatial learning than controls in the Morris water maze test, regardless of sex and stress duration. Males exposed to CRS for 11 days showed a higher rate of behaviors associated with anxiety than males exposed to 22 days of CRS at the elevated plus maze test, but the same was not observed in females. The weight gain of animals exposed to stress decreased in the first 11 days, showing a recovery from day 11 to day 22 of intervention. No effects of CRS were observed on behaviors associated with depression in the sucrose preference test. The results suggest habituation to the protocol, with a progressive decrease in the harmful effects of stress on and maintenance of the beneficial effects. It is possible that females are more resistant to the harmful effects of CRS on anxiety.

A relação com o saber nas atividades lúdicas escolares / The relationship with knowledge in school recreational activities / La relación con el saber en las actividades lúdicas escolares

O brincar é uma atividade importante para o desenvolvimento infantil, porque melhora aspectos cognitivos, emocionais e físicos. Além disso, jogos e brincadeiras podem ser explorados como recurso educacional. Partindo do entendimento da ludicidade enquanto um processo subjetivo, este trabalho investigou a relação com o saber estabelecida durante as brincadeiras, buscando compreendê-las em suas dimensões epistêmica, social e identitária. Dezesseis estudantes do 5º ano do ensino fundamental foram entrevistados a partir de um roteiro baseado no instrumento "balanço do saber", proposto por Bernard Charlot. As questões foram adaptadas para possibilitar apreender o que as crianças dizem aprender durante as brincadeiras em que participam, com ênfase naquelas realizadas em sala de aula. Os resultados da análise de conteúdo realizada mostraram que, apesar de existirem conflitos sobre como se estabelecem as funções lúdica e educativa, quando a brincadeira infantil é utilizada como recurso pedagógico, os sujeitos podem identificar benefícios no processo de aprendizagem por meio dela. Aponta-se, também, a necessidade de considerar a condição social da criança no ambiente escolar para o sucesso ao utilizar essas atividades como práticas pedagógicas.(AU)

Child's play is an important activity for child development since it improves cognition, emotional, and physical aspects. Games can also be explored as an educational resource. Starting from the understanding that playfulness is a subjective process, this work has investigated the relationship to the knowledge stablished during games, aiming to understand it in its epistemic, social, and identitary dimensions. A group of 16 5th grade students were interviewed from a script based on the instrument "balance of knowledge," as proposed by Bernard Charlot. The questions were adapted to enable the apprehension of what children say they learn on the games they play, emphasizing those which are played in classrooms. The results of the content analysis performed have showed that, despite the conflicts on how both playful and educative functions are stablished when child's play is used as a pedagogic resource, the subjects can identify benefits on the process of learning with it. The need to consider the child's social condition in the school environment to reach success when using these activities as pedagogical practices is also pointed out.(AU)

Jugar es una actividad importante para el desarrollo de los niños, porque mejora aspectos cognitivos, emocionales y físicos. Por tanto, los juegos son explorados como recurso educativo. Partiendo de la comprensión de que lo lúdico es un proceso subjetivo, este trabajo analizó la relación con el saber que se establece durante el juego, con el objetivo de comprenderlo en sus dimensiones epistémica, social e identitaria. Se entrevistó a dieciséis estudiantes de quinto grado a partir de un guion basado en el instrumento "balance del saber" propuesto por Bernard Charlot. Las preguntas fueron adaptadas para permitir la aprehensión de lo que los niños dicen que aprenden en sus juegos, enfatizando los que se juegan en las aulas. Los resultados del análisis de contenido realizado mostraron que, a pesar de que existen conflictos sobre cómo se establecen ambas funciones lúdica y educativa cuando se utiliza el juego infantil como recurso pedagógico, los niños pueden identificar beneficios en el proceso de aprendizaje a través del juego. Se señala la necesidad de considerar la condición social del niño en el entorno escolar para alcanzar el éxito al utilizar estas actividades como prácticas pedagógicas.(AU)

Persistence of Spatial Memory Induced by Spaced Training Involves a Behavioral-Tagging Process.

Spaced training, which involves long inter-trial intervals, has positive effects on memories. One of the main attributes of long-term memories (LTM) is persistence. Here, to identify the process that promotes LTM persistence by spaced learning, we used the spatial object recognition (SOR) task in rats. The protocol consisted of a first strong training session that induced LTM formation (tested 1 day after training), but not LTM persistence (tested 7 or 14 days after training); and a second weak training session that promoted memory persistence when applied 1 day, but not 7 days, after the first training. We propose that the promotion of memory persistence is based on the Behavioral Tagging (BT) mechanism operating when the memory trace is retrieved. BT involves the setting of a tag induced by learning which gives rise to input selectivity, and the use of plasticity-related proteins (PRPs) to establish the mnemonic trace. We postulate that retraining will mainly retag the sites initially activated by the original learning, where the PRPs needed for memory expression and/or induced by retrieval would be used to maintain a persistent mnemonic trace. Our results suggest that the mechanism of memory expression, but not those of memory reinforcement or reconsolidation, is necessary to promote memory persistence after retraining. The molecular mechanisms involve ERKs1/2 activity to set the SOR learning tag, and the availability of GluA2-containing AMPA receptor. In conclusion, both the synthesis of PRPs and the setting of learning tags are key processes triggered by retraining that allow SOR memory persistence.

Coumestrol pre-treatment improves spatial learning and memory deficits following transient cerebral ischemia recruiting hippocampal GluR2 AMPA receptors.

Transient global ischemia is a leading cause of learning and memory dysfunction and induces a pattern of delayed neuronal death in the CA1 subfield of the hippocampus by down-regulating GluR2 mRNA AMPA receptors in this cerebral area. This study sought to investigate the neuroprotective effect of coumestrol against spatial memory impairment induced by global ischemia that leads to neural death by reducing the GluR2 receptors content in the hippocampal CA1 area. Our studies demonstrated that coumestrol administration prevented spatial memory deficits in mice. These findings suggest a cognitive enhancement role of coumestrol against cognitive impairment in ischemic events.

Basolateral amygdala stimulation plus water maze training restore dentate gyrus LTP and improve spatial learning and memory.

Synaptic plasticity is a key mechanism of neural plasticity involved in learning and memory. A reduced or impaired synaptic plasticity could lead to a deficient learning and memory. On the other hand, besides reducing hipocampal dependent learning and memory, fimbria-fornix lesion affects LTP. However, we have consistently shown that stimulation of the basolateral amygdala (BLA) 15 min after water maze training is able to improve spatial learning and memory in fimbria fornix lesioned rats while also inducing changes in the expression of plasticity-related genes expression in memory associated brain regions like the hippocampus and prefrontal cortex. In this study we test that hypothesis: whether BLA stimulation 15 min after water maze training can improve LTP in the hippocampus of fimbria-fornix lesioned rats. To address this question, we trained fimbria-fornix lesioned rats in water maze for four consecutive days, and the BLA was bilaterally stimulated 15 min after each training session.Our data show that trained fimbria-fornix lesioned rats develop a partially improved LTP in dentated gyrus compared with the non-trained fimbria-fornix lesioned rats. In contrast, dentated gyrus LTP in trained and BLA stimulated fimbria-fornix lesioned rats improved significantly compared to the trained fimbria-fornix lesioned rats, but was not different from that shown by healthy animals. BLA stimulation in non-trained FF lesioned rats did not improve LTP; instead produces a transient synaptic depression. Restoration of the ability to develop LTP by the combination of training and BLA stimulation would be one of the mechanisms involved in ameliorating memory deficits in lesioned animals.

Spatial Learning Is Associated with Antagonist Outcomes for DNA Methylation and DNA Hydroxymethylation in the Transcriptional Regulation of the Ryanodine Receptor 3.

Increasing attention has been drawn to the role that intracellular calcium stores play in neuronal function. Ryr3 is an intracellular calcium channel that contributes to hippocampal long-term potentiation, dendritic spine function, and higher cognitive processes. Interestingly, stimuli that increase neuronal activity upregulate the transcriptional activity of Ryr3 and augment DNA methylation in its proximal promoter. However, if these observations are valid for complex behavioral tasks such as learning and memory remains being evaluated. Relative expression analysis revealed that spatial learning increased the hippocampal levels of Ryr3, whereas mice trained using a visible platform that resulted in no spatial association showed reduced expression. Interestingly, we also observed that specific DNA modifications accompanied these opposite transcriptional changes. Increased DNA methylation was observed in hippocampal samples from spatially trained mice, and increased DNA hydroxymethylation was found in samples from mice trained using a visible platform. Both DNA modifications were not altered in control regions, suggesting that these changes are not generalized, but rather specific modifications associated with this calcium channel's transcriptional regulation. Our two experimental groups underwent the same physical task differing only in the spatial learning component, highlighting the tight relationship between DNA modifications and transcriptional activity in a relevant context such as behavioral training. Our results complement previous observations and suggest that DNA modifications are a reliable signal for the transcriptional activity of Ryr3 and can be useful to understand how conditions such as aging and neuropathological diseases determine altered Ryr3 expression.

Effects of Gestational Diabetes in Cognitive Behavior, Oxidative Stress and Metabolism on the Second-Generation Off-Spring of Rats.

Gestational diabetes (GD) has a negative impact on neurodevelopment, resulting in cognitive and neurological deficiencies. Oxidative stress (OS) has been reported in the brain of the first-generation offspring of GD rats. OS has been strongly associated with neurodegenerative diseases. In this work, we determined the effect of GD on the cognitive behavior, oxidative stress and metabolism of second-generation offspring. GD was induced with streptozotocin (STZ) in pregnant rats to obtain first-generation offspring (F1), next female F1 rats were mated with control males to obtain second-generation offspring (F2). Two and six-month-old F2 males and females were employed. Anxious-type behavior, spatial learning and spatial working memory were evaluated. In cerebral cortex and hippocampus, the oxidative stress and serum biochemical parameters were measured. Male F2 GD offspring presented the highest level of anxiety-type behavior, whilst females had the lowest level of anxiety-type behavior at juvenile age. In short-term memory, adult females presented deficiencies. The offspring F2 GD females presented modifications in oxidative stress biomarkers in the cerebral cortex as lipid-peroxidation, oxidized glutathione and catalase activity. We also observed metabolic disturbances, particularly in the lipid and insulin levels of male and female F2 GD offspring. Our results suggest a transgenerational effect of GD on metabolism, anxiety-like behavior, and spatial working memory.

Serotonin and noradrenaline content and release in the dorsal hippocampus during learning and spatial memory in prenatally stressed rats.

Prenatal stress causes learning and spatial memory deficits in adulthood by modifying hippocampal function. The dorsal hippocampus contains serotonergic and noradrenergic neuron terminals, which are related to cognitive processes. It is currently unknown whether prenatal stress modifies serotonin (5-HT) and noradrenaline (NA) content and their release in the hippocampus during cognitive performance. Therefore, we measured these variables in the dorsal hippocampus of prenatally stressed males during spatial learning and memory tests. Cognitive tests were performed in 3-month-old control and prenatally stressed male rats in the Morris Water Maze (MWM). After cognitive tests, the dorsal hippocampus was dissected to quantify 5-HT and NA content. In other males, 5-HT and NA release in the dorsal hippocampus was assessed by microdialysis, before and after cognitive tests. Prenatally stressed males showed longer latencies to reach the platform, compared to control animals. Hippocampal 5-HT content decreased during learning and memory tasks in both groups, while NA content was not modified in prenatally stressed males neither before, nor after learning and memory tests. 5-HT and NA release were significantly lower in prenatally stressed animals during spatial learning and memory tasks. Corticosterone response was greater in prenatally stressed animals compared to controls. These results show that cognitive disruption caused by prenatal stress is related to decreased 5-HT and NA release, and to higher adrenal axis response in prenatally stressed animals.

Effects of long-lasting social isolation and re-socialization on cognitive performance and brain activity: a longitudinal study in Octodon degus.

Social isolation is considered a stressful situation that results in increased physiological reactivity to novel stimuli, altered behaviour, and impaired brain function. Here, we investigated the effects of long-term social isolation on working memory, spatial learning/memory, hippocampal synaptic transmission, and synaptic proteins in the brain of adult female and male Octodon degus. The strong similarity between degus and humans in social, metabolic, biochemical, and cognitive aspects, makes it a unique animal model that can be highly applicable for further social, emotional, cognitive, and aging studies. These animals were socially isolated from post-natal and post-weaning until adulthood. We also evaluated if re-socialization would be able to compensate for reactive stress responses in chronically stressed animals. We showed that long-term social isolation impaired the HPA axis negative feedback loop, which can be related to cognitive deficits observed in chronically stressed animals. Notably, re-socialization restored it. In addition, we measured physiological aspects of synaptic transmission, where chronically stressed males showed more efficient transmission but deficient plasticity, as the reverse was true on females. Finally, we analysed synaptic and canonical Wnt signalling proteins in the hypothalamus, hippocampus, and prefrontal cortex, finding both sex- and brain structure-dependent modulation, including transient and permanent changes dependent on stress treatment.

Modifications to cytoskeleton-associated proteins in dendritic spines underlie the adaptive plasticity involved in long term reference memory.

Spatial learning and memory enables individuals to orientate themselves in an external environment. Synaptic stimulation of dendritic spines on hippocampal place cells underlies adaptive cognitive performance, inducing plastic changes such as spinogenesis, pruning and structural interconversion. Such plastic changes are driven by complex molecular machinery that relies on several actin cytoskeleton-associated proteins (ACAP's), these interacting with actin filaments in the postsynaptic density to guide the conformational changes to spines in accordance with the synaptic information they receive. However, the specific dynamics of the plastic changes in spines driven by ACAP's are poorly understood. Adult rats exhibit efficient allocentric reference memory 30 days after training in a spatial learning paradigm in the Morris water maze. A Golgi study revealed this behavior to be associated with a reduction in both spine density and in mushroom spines, as well as a concomitant increase in thin spines. These changes were accompanied by the overexpression of mRNA encoding ß-actin, Spinophilin and Cortactin, whilst the expression of Profilin, α-actinin, Drebrin, Synaptopodin and Myosin decreased. By contrast, no changes were evident in Cofilin, Gelsolin and Arp2/3 mRNA. From this analysis, it appears that neither spinogenesis nor new mushroom spines are necessary for long-term spatial information retrieval, while thin spines could be potentiated to retrieve pre-learned spatial information. Further studies that focus on the signaling pathways and their related molecules may shed further light on the molecular dynamics of the plastic changes to dendritic spines that underlie cognitive performance, both under normal and pathological conditions.

Learning to find spatially reversed sounds.

Adaptation to systematic visual distortions is well-documented but there is little evidence of similar adaptation to radical changes in audition. We use a pseudophone to transpose the sound streams arriving at the left and right ears, evaluating the perceptual effects it provokes and the possibility of learning to locate sounds in the reversed condition. Blindfolded participants remain seated at the center of a semicircular arrangement of 7 speakers and are asked to orient their head towards a sound source. We postulate that a key factor underlying adaptation is the self-generated activity that allows participants to learn new sensorimotor schemes. We investigate passive listening conditions (very short duration stimulus not permitting active exploration) and dynamic conditions (continuous stimulus allowing participants time to freely move their heads or remain still). We analyze head movement kinematics, localization errors, and qualitative reports. Results show movement-induced perceptual disruptions in the dynamic condition with static sound sources displaying apparent movement. This effect is reduced after a short training period and participants learn to find sounds in a left-right reversed field for all but the extreme lateral positions where motor patterns are more restricted. Strategies become less exploratory and more direct with training. Results support the hypothesis that self-generated movements underlie adaptation to radical sensorimotor distortions.

Moderate exercise prevents the cell atrophy caused by hypothyroidism in rats.

Adult­onset hypothyroidism is associated with an increase in cell atrophy of the hippocampal pyramidal neurons. Physical exercise implies diverse actions on the neural tissue that promote neuron proliferation and survival. The beneficial effects of exercise seem to be inversely linked to its intensity, so that strenuous exercise has reduced protective effects. In this study we evaluated the capacity of a moderate forced­exercise routine to counteract the neurodegenerative effects of a hypothyroid condition induced during adulthood. Simultaneously with a chronic anti­thyroid chemical treatment, a group of rats was forced to walk in a motorized wheel for 30 min daily five times a week. In four weeks of treatment the rats developed a plain hypothyroid condition that in non­exercised rats was accompanied by a marked increase in the number of atrophic cells in all CA regions of the hippocampus. The forced­exercise treatment did not counter the development of hypothyroidism and its signs, but it did prevent almost completely the associated neuronal damage in all CA regions. The forced exercise also improved the cognitive function in a spatial­learning test. These results indicate that moderate exercise has the potential to prevent the structural and functional deficits associated with a hypothyroid condition.