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1.
Behav Brain Res ; 467: 115020, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38679144

ABSTRACT

Prolonged consumption of diets high in saturated fat and sugar has been related to obesity and overweight, which in turn are linked to cognitive impairment in both humans and rodents. This has become a current issue, especially in children and adolescents, because these stages are crucial to neurodevelopmental processes and programming of adult behavior. To evaluate the effects of gestational and early exposure to an obesogenic diet, three groups with different dietary patterns were established: high-fat and high-sucrose diet (HFS), standard diet (SD), and a dietary shift from a high-fat, high-sucrose diet to a standard diet after weaning (R). Spatial learning and behavioral flexibility in adult male and female Wistar rats were evaluated using the Morris water maze (MWM) at PND 60. Furthermore, regional brain oxidative metabolism was assessed in the prefrontal cortex and the hippocampus. Contrary to our hypothesis, the HFS diet groups showed similar performance on the spatial learning task as the other groups, although they showed impaired cognitive flexibility. The HFS group had increased brain metabolic capacity compared to that of animals fed the standard diet. Shifting from the HFS diet to the SD diet after weaning restored the brain metabolic capacity in both sexes to levels similar to those observed in animals fed the SD diet. In addition, animals in the R group performed similarly to those fed the SD diet in the Morris water maze in both tasks. However, dietary shift from HFS diet to standard diet after weaning had only moderate sex-dependent effects on body weight and fat distribution. In conclusion, switching from an HFS diet to a balanced diet after weaning would have beneficial effects on behavioral flexibility and brain metabolism, without significant sex differences.


Subject(s)
Brain , Diet, High-Fat , Prenatal Exposure Delayed Effects , Rats, Wistar , Weaning , Animals , Female , Male , Diet, High-Fat/adverse effects , Pregnancy , Rats , Brain/metabolism , Maze Learning/physiology , Dietary Sucrose/administration & dosage , Behavior, Animal/physiology , Prefrontal Cortex/metabolism , Hippocampus/metabolism
2.
Psicothema ; 36(2): 133-144, 2024 05.
Article in English | MEDLINE | ID: mdl-38661160

ABSTRACT

BACKGROUND: Exposure to early life stress (ELS) and maternal consumption of a high-fat and high-sugar diet can have detrimental effects on adult emotional responses. The microbiota and gut-brain axis have been proposed as playing a mediating role in the regulation of stress and emotion. METHOD: Young male rats were exposed to maternal separation (MS) together with maternal and postnatal consumption of a HFS diet (45%kcal saturated fat, 17%kcal sucrose). Anxiety-like behaviour was evaluated using an elevated zero-maze, and depression-like behaviour using the forced-swim and sucrose preference tests. Microbiota composition and derived metabolites were also analysed in faecal samples using a gas chromatograph and mass spectrometry. RESULTS: Combined exposure to MS and lifelong consumption of a HFS diet partially reversed the abnormal anxiety-like and depression-like behaviours in early adulthood caused by each adverse factor alone. Diet composition had a greater negative impact than ELS exposure on the gut microbiota, and both environmental factors interacted with microbiota composition partially counteracting their negative effects. CONCLUSIONS: The effects of exposure to early life stress and a HFS diet independently are partially reversed after the combination of both factors. These results suggest that ELS and diet interact to modulate adult stress response and gut microbiota.


Subject(s)
Anxiety , Depression , Diet, Western , Gastrointestinal Microbiome , Maternal Deprivation , Stress, Psychological , Animals , Male , Diet, Western/adverse effects , Rats , Anxiety/microbiology , Depression/microbiology , Emotions , Rats, Wistar , Female
3.
Psicothema (Oviedo) ; 36(2): 133-144, 2024. tab, graf
Article in English | IBECS | ID: ibc-VR-35

ABSTRACT

Background: Exposure to early life stress (ELS) and maternal consumption of a high-fat and high-sugar diet can have detrimental effects on adult emotional responses. The microbiota and gut-brain axis have been proposed as playing a mediating role in the regulation of stress and emotion. Method: Young male rats were exposed to maternal separation (MS) together with maternal and postnatal consumption of a HFS diet (45%kcal saturated fat, 17%kcal sucrose). Anxiety-like behaviour was evaluated using an elevated zero-maze, and depression-like behaviour using the forced-swim and sucrose preference tests. Microbiota composition and derived metabolites were also analysed in faecal samples using a gas chromatograph and mass spectrometry. Results: Combined exposure to MS and lifelong consumption of a HFS diet partially reversed the abnormal anxiety-like and depression-like behaviours in early adulthood caused by each adverse factor alone. Diet composition had a greater negative impact than ELS exposure on the gut microbiota, and both environmental factors interacted with microbiota composition partially counteracting their negative effects. Conclusions: The effects of exposure to early life stress and a HFS diet independently are partially reversed after the combination of both factors. These results suggest that ELS and diet interact to modulate adult stress response and gut microbiota.(AU)


Antecedentes: El estrés temprano (ET) y el consumo materno de una dieta alta en grasas y azúcares (HFS) pueden tener efectos perjudiciales sobre las respuestas emocionales en la adultez. La microbiota y el eje intestino-cerebro podrían mediar la regulación del estrés y las emociones. Método: Ratas macho jóvenes se expusieron a separación materna (SM) y a consumo materno y postnatal de una dieta HFS (45%kcal grasa saturada, 17%kcal sacarosa). Se evaluó el comportamiento ansioso mediante el laberinto cero elevado y el comportamiento depresivo mediante natación forzada y preferencia por sacarosa. Se analizó la microbiota en heces empleando cromatografía de gas y espectrometría de masas. Resultados: La exposición combinada a la SM y el consumo de una dieta HFS revirtió parcialmente la ansiedad y depresión en adultos causadas independientemente por cada factor adverso. La dieta influyó negativamente más que la exposición a ET en la microbiota y ambos factores modificaron su composición contrarrestando parcialmente sus efectos negativos. Conclusiones: Los efectos del ET y una dieta HFS por independiente varían con respecto a los efectos de la combinación de ambos factores, sugiriendo que el ET y la dieta interactúan modulando en el adulto la respuesta al estrés y la microbiota intestinal.(AU)


Subject(s)
Humans , Animals , Mice , Microbiota , Depression , Anxiety , Stress, Psychological , Dietary Sugars , Diet, High-Fat
4.
Physiol Behav ; 257: 113969, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36181786

ABSTRACT

Prolonged daily intake of Western-type diet rich in saturated fats and sugars, and exposure to early life stress have been independently linked to impaired neurodevelopment and behaviour in animal models. However, sex-specific effects of both environmental factors combined on spatial learning and memory, behavioural flexibility, and brain oxidative capacity have still not been addressed. The current study aimed to evaluate the impact of maternal and postnatal exposure to a high-fat and high-sugar diet (HFS), and exposure to early life stress by maternal separation in adult male and female Wistar rats. For this purpose, spatial learning and memory and behavioural flexibility were evaluated in the Morris water maze, and regional brain oxidative capacity and oxidative stress levels were measured in the hippocampus and medial prefrontal cortex. Spatial memory, regional brain oxidative metabolism, and levels of oxidative stress differed between females and males, suggesting sexual dimorphism in the effects of a HFS diet and early life stress. Males fed the HFS diet performed better than all other experimental groups independently of early life stress exposure. However, behavioural flexibility evaluated in the spatial reversal leaning task was impaired in males fed the HFS diet. In addition, exposure to maternal separation or the HFS diet increased the metabolic capacity of the prefrontal cortex and dorsal hippocampus in males and females. Levels of oxidative stress measured in the latter brain regions were also increased in groups fed the HFS diet, but maternal separation seemed to dampen regional brain oxidative stress levels. Therefore, these results suggest a compensatory effect resulting from the interaction between prolonged exposure to a HFS diet and early life stress.


Subject(s)
Brain , Maze Learning , Sex Characteristics , Spatial Learning , Animals , Female , Male , Rats , Brain/metabolism , Diet, High-Fat , Diet, Western/adverse effects , Hippocampus/metabolism , Maternal Deprivation , Rats, Wistar , Stress, Psychological
5.
Article in English | MEDLINE | ID: mdl-34973413

ABSTRACT

Gender is considered as a pivotal determinant of mental health. Indeed, several psychiatric disorders such as anxiety and depression are more common and persistent in women than in men. In the past two decades, impaired brain energy metabolism has been highlighted as a risk factor for the development of these psychiatric disorders. However, comprehensive behavioural and neurobiological studies in brain regions relevant to anxiety and depression symptomatology are scarce. In the present study, we summarize findings describing cannabidiol effects on anxiety and depression in maternally separated female mice as a well-established rodent model of early-life stress associated with many mental disorders. Our results indicate that cannabidiol could prevent anxiolytic- and depressive-related behaviour in early-life stressed female mice. Additionally, maternal separation with early weaning (MSEW) caused long-term changes in brain oxidative metabolism in both nucleus accumbens and amygdalar complex measured by cytochrome c oxidase quantitative histochemistry. However, cannabidiol treatment could not revert brain oxidative metabolism impairment. Moreover, we identified hyperphosphorylation of mTOR and ERK 1/2 proteins in the amygdala but not in the striatum, that could also reflect altered brain intracellular signalling related with to bioenergetic impairment. Altogether, our study supports the hypothesis that MSEW induces profound long-lasting molecular changes in mTOR signalling and brain energy metabolism related to depressive-like and anxiety-like behaviours in female mice, which were partially ameliorated by CBD administration.


Subject(s)
Anticonvulsants/administration & dosage , Anxiety/drug therapy , Cannabidiol/administration & dosage , Emotions/physiology , Maternal Deprivation , Nucleus Accumbens/drug effects , Amygdala/drug effects , Animals , Behavior, Animal , Brain/metabolism , Disease Models, Animal , Female , Mice , TOR Serine-Threonine Kinases/genetics , Weaning
6.
Neurobiol Learn Mem ; 187: 107561, 2022 01.
Article in English | MEDLINE | ID: mdl-34838984

ABSTRACT

INTRODUCTION: The neuropeptide Y (NPY) is broadly distributed in the central nervous system (CNS), and it has been related to neuroprotective functions. NPY seems to be an important component to counteract brain damage and cognitive impairment mediated by drugs of abuse and neurodegenerative diseases, and both NPY and its Y2 receptor (Y2R) are highly expressed in the hippocampus, critical for learning and memory. We have recently demonstrated its influence on cognitive functions; however, the specific mechanism and involved brain regions where NPY modulates spatial memory by acting on Y2R remain unclear. METHODS: Here, we examined the involvement of the hippocampal NPY Y2R in spatial memory and associated changes in brain metabolism by bilateral administration of the selective antagonist BIIE0246 into the rat dorsal hippocampus. To further evaluate the relationship between memory functions and neuronal activity, we analysed the regional expression of the mitochondrial enzyme cytochrome c oxidase (CCO) as an index of oxidative metabolic capacity in limbic and non-limbic brain regions. RESULTS: The acute blockade of NPY Y2R significantly improved spatial memory recall in rats trained in the Morris water maze that matched metabolic activity changes in spatial memory processing regions. Specifically, CCO activity changes were found in the dentate gyrus of the dorsal hippocampus and CA1 subfield of the ventral hippocampus, the infralimbic region of the PFC and the mammillary bodies. CONCLUSIONS: These findings suggest that the NPY hippocampal system, through its Y2R receptor, influences spatial memory recall (retrieval) and exerts control over patterns of brain activation that are relevant for associative learning, probably mediated by Y2R modulation of long-term potentiation and long-term depression.


Subject(s)
Hippocampus/metabolism , Mental Recall/physiology , Neuropeptide Y/metabolism , Receptors, Neuropeptide Y/metabolism , Spatial Memory/physiology , Animals , Brain/metabolism , Limbic System/metabolism , Male , Morris Water Maze Test , Neuronal Plasticity , Neurons/metabolism , Rats
8.
Behav Brain Res ; 396: 112864, 2021 01 01.
Article in English | MEDLINE | ID: mdl-32827566

ABSTRACT

Neuropeptide Y (NPY) is highly abundant in the brain and is released as a co-transmitter with plasticity-related neurotransmitters such as glutamate, GABA and noradrenaline. Functionally, its release is associated with appetite, anxiety, and stress regulation. NPY acting on Y2 receptors (Y2R), facilitates fear extinction, suggesting a role in associative memory. Here, we explored to what extent NPY action at Y2R contributes to hippocampus-dependent spatial memory and found that dorsal intrahippocampal receptor antagonism improved spatial reference memory acquired in a water maze in rats, without affecting anxiety levels, or spontaneous motor activity. Water maze training resulted in an increase of Y2R, but not Y1R expression in the hippocampus. By contrast, in the prefrontal cortex there was a decrease in Y2R, and an increase of Y1R expression. Our results indicate that neuropeptide Y2R are significantly involved in hippocampus-dependent spatial memory and that receptor expression is dynamically regulated by this learning experience. Effects are consistent with a metaplastic contribution of NPY receptors to cumulative spatial learning.


Subject(s)
Extinction, Psychological/physiology , Hippocampus/metabolism , Maze Learning/physiology , Prefrontal Cortex/metabolism , Receptors, Neuropeptide Y/metabolism , Spatial Memory/physiology , Animals , Behavior, Animal/drug effects , Behavior, Animal/physiology , Extinction, Psychological/drug effects , Hippocampus/drug effects , Male , Maze Learning/drug effects , Prefrontal Cortex/drug effects , Rats , Rats, Wistar , Receptors, Neuropeptide Y/antagonists & inhibitors , Spatial Memory/drug effects
9.
Front Psychol ; 11: 564413, 2020.
Article in English | MEDLINE | ID: mdl-33329193

ABSTRACT

The Western diet (WD) pattern characterized by high daily intake of saturated fats and refined carbohydrates often leads to obesity and overweight, and it has been linked to cognitive impairment and emotional disorders in both animal models and humans. This dietary pattern alters the composition of gut microbiota, influencing brain function by different mechanisms involving the gut-brain axis. In addition, long-term exposure to highly palatable foods typical of WD could induce addictive-like eating behaviors and hypothalamic-pituitary-adrenal (HPA) axis dysregulation associated with chronic stress, anxiety, and depression. In turn, chronic stress modulates eating behavior, and it could have detrimental effects on different brain regions such as the hippocampus, hypothalamus, amygdala, and several cortical regions. Moreover, obesity and overweight induce neuroinflammation, causing neuronal dysfunction. In this review, we summarize the current scientific evidence about the mechanisms and factors relating WD consumption with altered brain function and behavior. Possible therapeutic interventions and limitations are also discussed, aiming to tackle and prevent this current pandemic.

10.
Brain Sci ; 10(7)2020 Jul 14.
Article in English | MEDLINE | ID: mdl-32674298

ABSTRACT

Sex differences have been reported in the susceptibility to early life stress and its neurobiological correlates in humans and experimental animals. However, most of the current research with animal models of early stress has been performed mainly in males. In the present study, prolonged maternal separation (MS) paradigm was applied as an animal model to resemble the effects of adverse early experiences in male and female rats. Regional brain mitochondrial function, monoaminergic activity, and neuroinflammation were evaluated as adults. Mitochondrial energy metabolism was greatly decreased in MS females as compared with MS males in the prefrontal cortex, dorsal hippocampus, and the nucleus accumbens shell. In addition, MS males had lower serotonin levels and increased serotonin turnover in the prefrontal cortex and the hippocampus. However, MS females showed increased dopamine turnover in the prefrontal cortex and increased norepinephrine turnover in the striatum, but decreased dopamine turnover in the hippocampus. Sex differences were also found for pro-inflammatory cytokine levels, with increased levels of TNF-α and IL-6 in the prefrontal cortex and hippocampus of MS males, and increased IL-6 levels in the striatum of MS females. These results evidence the complex sex- and brain region-specific long-term consequences of early life stress.

11.
PLoS One ; 14(12): e0226377, 2019.
Article in English | MEDLINE | ID: mdl-31830106

ABSTRACT

Early life stress is associated with long-term and pervasive adverse effects on neuroendocrine development, affecting normal cognitive and emotional development. Experimental manipulations like environmental enrichment (EE) may potentially reverse the effects of early life stress induced by maternal separation (MS) paradigm in rodents. However, the functional brain networks involved in the effects of EE after prolonged exposure to MS have not yet been investigated. In order to evaluate possible changes in brain functional connectivity induced by EE after MS, quantitative cytochrome c oxidase (CCO) histochemistry was applied to determine regional brain oxidative metabolism in adult male rats. Unexpectedly, results show that prolonged MS during the entire weaning period did not cause any detrimental effects on spatial learning and memory, including depressive-like behavior evaluated in the forced-swim test, and decreased anxiety-like behavior. However, EE seemed to alter anxiety- and depression-like behaviors in both control and MS groups, but improved spatial memory in the latter groups. Analysis of brain CCO activity showed significantly lower metabolic capacity in most brain regions selected in EE groups probably associated with chronic stress, but no effects of MS on brain metabolic capacity. In addition, principal component analysis of CCO activity revealed increased large-scale functional brain connectivity comprising at least three main networks affected by EE in both MS and control groups. Moreover, EE induced a pattern of functional brain connectivity associated with stress and anxiety-like behavior as compared with non-enriched groups. In conclusion, EE had differential effects on cognition and emotional behavior irrespective of exposure to MS. In view of the remarkable effects of EE on brain function and behavior, implementation of rodent housing conditions should be optimized by evaluating the balance between scientific validity and animal welfare.


Subject(s)
Anxiety/physiopathology , Behavior, Animal , Brain/physiopathology , Environment , Nerve Net , Stress, Psychological , Animals , Animals, Newborn , Female , Male , Maternal Deprivation , Rats , Rats, Wistar , Spatial Learning
12.
Psicothema (Oviedo) ; 31(1): 46-52, feb. 2019. graf, ilus, tab
Article in English | IBECS | ID: ibc-181932

ABSTRACT

Background: Exposure to maternal separation (MS) in rodents may have long-lasting consequences for the structure and function of several brain regions, eventually associated with alterations in cognition and emotion later in life. Post-weaning environmental enrichment (EE) has been reported to ameliorate the detrimental effects of exposure to early life stress mainly in the hippocampus. Method: In vivo magnetic resonance imaging (MRI) was applied to evaluate possible volumetric changes in the dorsal and ventral hippocampus, the medial prefrontal cortex and the dorsal striatum of 90-day-old male rats after daily MS for 240 min from postnatal days 2-21. Results: No significant volume changes were found in the selected brain regions in MS animals as compared with an age-matched control group. However, additional groups of control and MS animals with EE from days 21-60 showed significant volume increases in the medial prefrontal cortex and the ventral hippocampus as compared to the groups without EE. In addition, general hemispheric asymmetry was found in the volume of the brain regions measured. Conclusions: Our results demonstrate that EE could have differential effects depending on previous exposure to MS and on the development of brain lateralization


Antecedentes: la exposición a separación materna (MS) en roedores puede tener consecuencias a largo plazo en la estructura y función de regiones cerebrales, particularmente asociadas con alteraciones cognitivas y emocionales. El enriquecimiento ambiental (EE) tras la lactancia ha mostrado contrarrestar los efectos adversos de la exposición a estrés temprano principalmente en el hipocampo. Método: se obtuvieron imágenes por resonancia magnética (IRM) in vivo para evaluar los posibles cambios volumétricos en el hipocampo dorsal y ventral, la corteza prefrontal medial y el estriado dorsal en ratas macho de 90 días de edad tras MS durante 240 min diarios entre los días 2 y 21. Resultados: no hallamos cambios significativos de volumen en las regiones cerebrales seleccionadas de animales MS, frente a un grupo control. Sin embargo, grupos adicionales de animales control y MS con EE entre los días 21-60 mostraron incrementos volumétricos significativos en la corteza prefrontal medial y el hipocampo ventral, frente a grupos sin EE. Asimismo, se encontró asimetría hemisférica en el volumen de las regiones cerebrales medidas. Conclusiones: nuestros resultados demuestran que el EE tendría efectos diferenciales dependiendo de la exposición previa a la MS y en el desarrollo de la lateralización cerebral


Subject(s)
Animals , Male , Female , Rats , Cerebrum/growth & development , Maternal Deprivation , Animals, Newborn , Organ Size , Random Allocation , Rats, Wistar , Social Environment , Stress, Psychological
13.
Psicothema ; 31(1): 46-52, 2019 Feb.
Article in English | MEDLINE | ID: mdl-30664410

ABSTRACT

BACKGROUND: Exposure to maternal separation (MS) in rodents may have long-lasting consequences for the structure and function of several brain regions, eventually associated with alterations in cognition and emotion later in life. Post-weaning environmental enrichment (EE) has been reported to ameliorate the detrimental effects of exposure to early life stress mainly in the hippocampus. METHOD: In vivo magnetic resonance imaging (MRI) was applied to evaluate possible volumetric changes in the dorsal and ventral hippocampus, the medial prefrontal cortex and the dorsal striatum of 90-day-old male rats after daily MS for 240 min from postnatal days 2-21. RESULTS: No significant volume changes were found in the selected brain regions in MS animals as compared with an age-matched control group. However, additional groups of control and MS animals with EE from days 21-60 showed significant volume increases in the medial prefrontal cortex and the ventral hippocampus as compared to the groups without EE. In addition, general hemispheric asymmetry was found in the volume of the brain regions measured. CONCLUSIONS: Our results demonstrate that EE could have differential effects depending on previous exposure to MS and on the development of brain lateralization.


Subject(s)
Brain/growth & development , Maternal Deprivation , Stress, Psychological , Animals , Animals, Newborn , Female , Male , Organ Size , Random Allocation , Rats , Rats, Wistar , Social Environment
14.
Prog Neuropsychopharmacol Biol Psychiatry ; 84(Pt A): 237-249, 2018 06 08.
Article in English | MEDLINE | ID: mdl-29526773

ABSTRACT

Prenatal and perinatal alcohol exposure caused by maternal alcohol intake during gestation and lactation periods can have long-lasting detrimental effects on the brain development and behaviour of offspring. Children diagnosed with Foetal Alcohol Spectrum Disorders (FASD) display a wide range of cognitive, emotional and motor deficits, together with characteristic morphological abnormalities. Maternal alcohol binge drinking is particularly harmful for foetal and early postnatal brain development, as it involves exposure to high levels of alcohol over short periods of time. However, little is known about the long-term effects of maternal alcohol binge drinking on brain function and behaviour. To address this issue, we used pregnant C57BL/6 female mice with time-limited access to a 20% v/v alcohol solution as a procedure to model alcohol binge drinking during gestation and lactational periods. Male offspring were behaviourally tested during adolescence (30 days) and adulthood (60 days), and baseline neural metabolic capacity of brain regions sensitive to alcohol effects were also evaluated in adult animals from both groups. Our results show that prenatal and postnatal alcohol exposure caused age-dependent changes in spontaneous locomotor activity, increased anxiety-like behaviour and attenuated alcohol-induced conditioned place preference in adults. Also, significant changes in neural metabolic capacity using cytochrome c oxidase (CCO) quantitative histochemistry were found in the hippocampal dentate gyrus, the mammillary bodies, the ventral tegmental area, the lateral habenula and the central lobules of the cerebellum in adult mice with prenatal and postnatal alcohol exposure. In addition, the analysis of interregional CCO activity correlations in alcohol-exposed adult mice showed disrupted functional brain connectivity involving the limbic, brainstem, and cerebellar regions. Finally, increased neurogenesis was found in the dentate gyrus of the hippocampus of alcohol-exposed offspring, suggesting neuroadaptive effects due to early alcohol exposure. Our results demonstrate that maternal binge-like alcohol drinking causes long-lasting effects on motor and emotional-related behaviours associated with impaired neuronal metabolic capacity and altered functional brain connectivity.


Subject(s)
Binge Drinking/complications , Brain/physiopathology , Fetal Alcohol Spectrum Disorders/etiology , Fetal Alcohol Spectrum Disorders/physiopathology , Animals , Anxiety/etiology , Anxiety/pathology , Anxiety/physiopathology , Binge Drinking/physiopathology , Brain/drug effects , Brain/growth & development , Brain/pathology , Disease Models, Animal , Electron Transport Complex IV/metabolism , Female , Male , Mice, Inbred C57BL , Motor Activity/drug effects , Motor Activity/physiology , Neural Pathways/drug effects , Neural Pathways/growth & development , Neural Pathways/pathology , Neural Pathways/physiopathology , Neurogenesis/drug effects , Neurons/drug effects , Neurons/pathology , Neurons/physiology , Random Allocation
15.
Hippocampus ; 26(10): 1265-75, 2016 10.
Article in English | MEDLINE | ID: mdl-27102086

ABSTRACT

Previous studies showed the involvement of brain regions associated with both spatial learning and associative learning in spatial memory extinction, although the specific role of the dorsal and ventral hippocampus and the extended hippocampal system including the mammillary body in the process is still controversial. The present study aimed to identify the involvement of the dorsal and ventral hippocampus, together with cortical regions, the amygdaloid nuclei, and the mammillary bodies in the extinction of a spatial memory task. To address these issues, quantitative cytochrome c oxidase histochemistry was applied as a metabolic brain mapping method. Rats were trained in a reference memory task using the Morris water maze, followed by an extinction procedure of the previously acquired memory task. Results show that rats learned successfully the spatial memory task as shown by the progressive decrease in measured latencies to reach the escape platform and the results obtained in the probe test. Spatial memory was subsequently extinguished as shown by the descending preference for the previously reinforced location. A control naïve group was added to ensure that brain metabolic changes were specifically related with performance in the spatial memory extinction task. Extinction of the original spatial learning task significantly modified the metabolic activity in the dorsal and ventral hippocampus, the amygdala and the mammillary bodies. Moreover, the ventral hippocampus, the lateral mammillary body and the retrosplenial cortex were differentially recruited in the spatial memory extinction task, as shown by group differences in brain metabolic networks. These findings provide new insights on the brain regions and functional brain networks underlying spatial memory, and specifically spatial memory extinction. © 2016 Wiley Periodicals, Inc.


Subject(s)
Extinction, Psychological/physiology , Hippocampus/metabolism , Spatial Memory/physiology , Amygdala/metabolism , Animals , Cerebral Cortex/metabolism , Electron Transport Complex IV/metabolism , Male , Mammillary Bodies/metabolism , Maze Learning/physiology , Neural Pathways/metabolism , Neuropsychological Tests , Random Allocation , Rats, Wistar
16.
Neurobiol Learn Mem ; 114: 165-70, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24937013

ABSTRACT

Visual discrimination tasks have been widely used to evaluate many types of learning and memory processes. However, little is known about the brain regions involved at different stages of visual discrimination learning. We used cytochrome c oxidase histochemistry to evaluate changes in regional brain oxidative metabolism during visual discrimination learning in a water-T maze at different time points during training. As compared with control groups, the results of the present study reveal the gradual activation of cortical (prefrontal and temporal cortices) and subcortical brain regions (including the striatum and the hippocampus) associated to the mastery of a simple visual discrimination task. On the other hand, the brain regions involved and their functional interactions changed progressively over days of training. Regions associated with novelty, emotion, visuo-spatial orientation and motor aspects of the behavioral task seem to be relevant during the earlier phase of training, whereas a brain network comprising the prefrontal cortex was found along the whole learning process. This study highlights the relevance of functional interactions among brain regions to investigate learning and memory processes.


Subject(s)
Brain/physiology , Discrimination Learning/physiology , Maze Learning/physiology , Nerve Net/physiology , Visual Perception/physiology , Animals , Electron Transport Complex IV/metabolism , Male , Orientation/physiology , Rats , Rats, Wistar
17.
Neurosci Lett ; 555: 182-6, 2013 Oct 25.
Article in English | MEDLINE | ID: mdl-24084195

ABSTRACT

Several studies have reported the brain regions involved in response learning. However, there is discrepancy regarding the lighting conditions in the experimental setting (i.e. under dark or light conditions). In this regard, it would be relevant to know if the presence/absence of visual cues in the environment has any effect in the brain networks involved in a response learning task. Animals were trained in a water T-maze under two different lighting conditions (light versus dark). All subjects reached the learning criterion of 80% correct arm choices. Quantitative cytochrome oxidase (CO) histochemistry was used as a metabolic brain mapping technique. Our results show that the ventral hippocampus and the parietal cortex are associated with the acquisition of a response learning task regardless of lighting conditions. In addition, when the same task is run in the dark, widespread recruitment of structures involving cortical, limbic and striatal regions was found.


Subject(s)
Brain/physiology , Learning/physiology , Lighting , Animals , Brain/enzymology , Darkness , Electron Transport Complex IV/metabolism , Male , Maze Learning , Rats , Rats, Wistar , Reaction Time
18.
PLoS One ; 8(5): e64749, 2013.
Article in English | MEDLINE | ID: mdl-23724089

ABSTRACT

Functional inactivation techniques enable studying the hippocampal involvement in each phase of spatial memory formation in the rat. In this study, we applied tetrodotoxin unilaterally or bilaterally into the dorsal hippocampus to evaluate the role of this brain structure in retrieval of memories acquired 28 days before in the Morris water maze. We combined hippocampal inactivation with the assessment of brain metabolism using cytochrome oxidase histochemistry. Several brain regions were considered, including the hippocampus and other related structures. Results showed that both unilateral and bilateral hippocampal inactivation impaired spatial memory retrieval. Hence, whereas subjects with bilateral hippocampal inactivation showed a circular swim pattern at the side walls of the pool, unilateral inactivation favoured swimming in the quadrants adjacent to the target one. Analysis of cytochrome oxidase activity disclosed regional differences according to the degree of hippocampal functional blockade. In comparison to control group, animals with bilateral inactivation showed increased CO activity in CA1 and CA3 areas of the hippocampus during retrieval, while the activity of the dentate gyrus substantially decreased. However, unilateral inactivated animals showed decreased CO activity in Ammon's horn and the dentate gyrus. This study demonstrated that retrieval recruits differentially the hippocampal subregions and the balance between them is altered with hippocampal functional lesions.


Subject(s)
Hippocampus/metabolism , Hippocampus/physiopathology , Memory, Long-Term/drug effects , Tetrodotoxin/toxicity , Animals , Behavior, Animal/drug effects , Electron Transport Complex IV/metabolism , Hippocampus/drug effects , Hippocampus/pathology , Learning Curve , Male , Rats , Rats, Wistar
19.
Psicothema (Oviedo) ; 25(1): 3-12, ene.-mar. 2013.
Article in English | IBECS | ID: ibc-108589

ABSTRACT

Background: Epigenetics is changing the widely accepted linear conception of genome function by explaining how environmental and psychological factors regulate the activity of our genome without involving changes in the DNA sequence. Research has identified epigenetic mechanisms mediating between environmental and psychological factors that contribute to normal and abnormal behavioral development. Method: the emerging field of epigenetics as related to psychology is reviewed. Results: the relationship between genes and behavior is reconsidered in terms of epigenetic mechanisms acting after birth and not only prenatally, as traditionally held. Behavioral epigenetics shows that our behavior could have long-term effects on the regulation of the genome function. In addition, epigenetic mechanisms would be related to psychopathology, as in the case of schizophrenia. In the latter case, it would be especially relevant to consider epigenetic factors such as life adversities (trauma, disorganized attachment, etc.) as related to its clinical manifestations, rather than genetic factors. Moreover, epigenetics implies overcoming classical dualist dichotomies such as nature-nurture, genotype-phenotype or pathogenesis-pathoplasty. Conclusions: In general, it can be stated that behavior and environment will finally take on a leading role in human development through epigenetic mechanisms (AU)


La epigenética está cambiando la concepción lineal que se suele tener de la genética al mostrar cómo eventos ambientales y psicológicos regulan la actividad de nuestro genoma sin implicar modificación en la secuencia de ADN. La investigación ha identificado mecanismos epigenéticos que juegan un papel mediador entre eventos ambientales y psicológicos y el desarrollo normal y alterado. Método: el artículo revisa el campo emergente de la epigenética y sus implicaciones para la psicología. Resultados: entre sus implicaciones destacan la reconsideración de la relación entre genes y conducta en términos de procesos epigenéticos que acontecen a lo largo de la vida y no solo prenatalmente como se asumía. La epigenética conductual muestra que nuestra conducta puede tener efectos a largo plazo sobre la función genómica. Otra implicación concierne a la psicopatología, señaladamente a la esquizofrenia. Más que de causas genéticas, habría que hablar de mediadores epigenéticos entre las adversidades de la vida (trauma, apego desorganizado) y formas clínicas. Asimismo, la epigenética implica la superación de dicotomías dualistas como herencia-medio, genotipo-fenotipo y patogenia-patoplastia. Conclusiones: en general, se puede decir que la conducta y el ambiente asumirán finalmente un papel protagonista en el desarrollo humano mediante mecanismos epigenéticos (AU)


Subject(s)
Humans , Male , Female , Genetics, Behavioral/ethics , Genetics, Behavioral/instrumentation , Genetics, Behavioral/organization & administration , DNA/analysis , Psychopathology/methods , Memory/physiology , Schizophrenia/genetics , Schizophrenic Psychology , Genetics, Behavioral/legislation & jurisprudence , Genetics, Behavioral/methods , Genetics, Behavioral/standards
20.
Psicothema ; 25(1): 3-12, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23336536

ABSTRACT

BACKGROUND: Epigenetics is changing the widely accepted linear conception of genome function by explaining how environmental and psychological factors regulate the activity of our genome without involving changes in the DNA sequence. Research has identified epigenetic mechanisms mediating between environmental and psychological factors that contribute to normal and abnormal behavioral development. METHOD: the emerging field of epigenetics as related to psychology is reviewed. RESULTS: the relationship between genes and behavior is reconsidered in terms of epigenetic mechanisms acting after birth and not only prenatally, as traditionally held. Behavioral epigenetics shows that our behavior could have long-term effects on the regulation of the genome function. In addition, epigenetic mechanisms would be related to psychopathology, as in the case of schizophrenia. In the latter case, it would be especially relevant to consider epigenetic factors such as life adversities (trauma, disorganized attachment, etc.) as related to its clinical manifestations, rather than genetic factors. Moreover, epigenetics implies overcoming classical dualist dichotomies such as nature-nurture, genotype-phenotype or pathogenesis-pathoplasty. CONCLUSIONS: In general, it can be stated that behavior and environment will finally take on a leading role in human development through epigenetic mechanisms.


Subject(s)
Epigenomics , Behavior , Genes , Humans , Mental Disorders/genetics , Schizophrenia/genetics
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