Maria Clotilde Tavares

Working and reference memory across the estrous cycle of rat: A long-term study in gonadally intact females

The results of many studies conducted over the past two decades suggested a role of estrogen on mammals ability to learn and remember. In the present paper, we analyzed the influence that the endogenous fluctuation of estrogen, naturally present across the different phases of estrous cycle of female rats, can exert over the performance of tasks utilized to assess memory. In particular, we analyzed the performances in an eight arms radial maze task, dependent upon working memory, and in a water maze (WM) task, dependent upon spatial reference memory. The water maze is aversively motivated by the desire to escape onto a safe platform, whereas the radial arm maze (RAM) is motivated by food reward. The difference in reinforcement may affect the speed of learning, the strategy adopted and the necessity for accurate navigation. Therefore, coherent results obtained through the two different tasks can be due to mnemonic factors. The study was conducted during a long period of time, 14 months, utilizing gonadally intact females, without pharmacological and surgical treatments. In order to evaluate the post-acquisition phase we first trained the animals to reach the criterion in performing tasks, and then we submitted them to experimental phase. Our results show that estrogen can have an effect on memory processes, and that this effect may be different in relation to different kinds of memory. In fact, in our study, estrogen selectively improved working memory, but not reference memory, during post-acquisition performance of a RAM task with four baited and four un-baited arms. Moreover, WM performances showed that estrogen have a negative effect on spatial reference memory.

Working memory for emotional facial expressions: Role of the estrogen in young women.

Physiological hormonal fluctuations during the menstrual cycle, postpartum, and menopause have been implicated in the modulation of mood, cognition, and affective disorders. Taking into account that womens performance in memory tasks can also fluctuate with circulating hormones levels across the menstrual cycle, the cognitive performance in a working memory task for emotional facial expressions, using the six basic emotions as stimuli in the delayed matching-to-sample, was evaluated in young women in different phases of the menstrual cycle. Our findings suggest that high levels of estradiol in the follicular phase could have a negative effect on delayed matching-to-sample working memory task, using stimuli with emotional valence. Moreover, in the follicular phase, compared to the menstrual phase, the percent of errors was significantly higher for the emotional facial expressions of sadness and disgust. The evaluation of the response times (time employed to answer) for each facial expression with emotional valence showed a significant difference between follicular and luteal in reference to the emotional facial expression of sadness. Our results show that high levels of estradiol in the follicular phase could impair the performance of working memory. However, this effect is specific to selective facial expressions suggesting that, across the phases of the menstrual cycle, in which conception risk is high, women could give less importance to the recognition of the emotional facial expressions of sadness and disgust. This study is in agreement with research conducted on non-human primates, showing that fluctuations of ovarian hormones across the menstrual cycle influence a variety of social and cognitive behaviors. Moreover, our data could also represent a useful tool for investigating emotional disturbances linked to menstrual cycle phases and menopause in women.

Sex-related lateralized effect of emotional content on declarative memory: an event related potential study.

Several studies suggest that emotional arousal can promote memory storage. In this study, we evaluated the effects of emotional content on declarative memory, utilizing an adaptation of two versions of the same story, with different arousing properties (neutral or emotional), which have been already employed in experiments involving the enhancing effects of emotions on memory retention. We used event related potentials (ERP) to evaluate whether there is a sex-related hemispheric lateralization of electrical potentials elicited by the emotional content of a story. We compared left and right hemisphere P300 waves, recorded in P3 and P4 electrode sites, in response to emotional or neutral stimuli in men and women. In the left hemisphere, emotional stimuli elicited a stronger P300 in women, compared to men, as indexed by both amplitude and latency measures; moreover, the emotional content of the story elicited a stronger P300 in the right hemisphere in men than in women. The better memory for the arousal material may be related to the differential P300 at encoding. These data indicate that both sex and cerebral hemisphere constitute important, interacting influences on neural correlates of emotion, and of emotionally influenced memory.

Superior colliculus lesions impair threat responsiveness in infant capuchin monkeys.

The ability to react fast and efficiently in threatening situations is paramount for the survival of organisms and has been decisive in our evolutionary history. Defense mechanisms in primates rely on the fast recognition of potential predators and facial expressions of conspecifics. The neural circuitry responsible for the detection of threat is generally thought to be centered on the amygdala. Although it is a pivotal structure in the processing of emotional stimuli, the amygdala does not seem necessary for the early stages of this process. Here we show that bilateral neurotoxic lesions of the superior colliculus in infant capuchins monkeys impaired the recognition of a rubber-snake in a threat-reward conflict task. Lesioned monkeys were uninhibited by a snake in a food-reward retrieval task. Lack of inhibition in the task was observed over the course of 15 weeks. The long lasting recognition impairment of a natural predator observed here is similar to the tameness aspects of Kluver-Bucy syndrome, indicating an important role of this structure in threat recognition.

Estrogen, cognitive functions and emotion: an overview on humans, non-human primates and rodents in reproductive years

Abstract Accumulating evidence has highlighted a number of important, global issues regarding the influence of estrogen on emotion and cognitive functions, including learning and memory processes, both in animal models and humans. The influence of estrogen on cognition and emotion can be explained by taking into account its modulator role on several neurotransmitter systems, acetylcholine in particular, but also catecholamines, serotonin and GABA in rodents, primates and humans. Another reason may lie in the widespread presence of the two classes (α and β) of estrogen receptors in many brain regions involved in emotion and cognition, including the hippocampal formation, amygdala and cerebral cortex. The present review reports on research conducted in our laboratory and others with the objective of identifying the action of estrogens on cognition and emotion in rodents, monkeys and humans in youth. In particular, the first section, focused on the mechanisms of estrogens action in the brain, illustrates the involvement of estrogen receptors and neurotransmitters in the cognitive and emotional processes; the second section deals with the estrogen effects on cognitive and emotional mechanisms, with particular emphasis on memory and the involvement of estrogen in emotion and cognition across the estrous/menstrual cycle.

The Müller-Lyer illusion as a tool for schizophrenia screening.

The perceptual deficit hypothesis for schizophrenia is based on more general models of normal human visual perception, which have traditionally postulated that objects must compete for attention and processing space in the visual system. Recent evidence suggests that susceptibility of schizophrenics to the Müller-Lyer (ML) illusion may be a marker of vulnerability, detectable in prodromic patients, but disappearing with the progression of the illness. This illusion consists of overestimating the length of a straight line with converging arrowheads at the ends, while underestimating those with diverging arrowheads. Although the ML illusion has been shown to occur in touch as well as vision, it is not known whether abnormal contextual suppression extends to other sensory modalities in schizophrenics. Another challenge consists in verifying whether different visual parameters of the illusion which favor the magnocellular and parvocellular systems would have diverse ML illusion effects in schizophrenia. In this review we present data showing the degree of illusion in capuchin monkeys (Cebus spp.), a possible animal model for schizophrenia. To this end, a computer program was developed to conduct experiments in humans and non-human primates, allowing the display of illusory figures, manipulation of the stimulis exposure time, interval between stimuli and number of trials. In the non-primate experiments, the visual illusion test based on achromatic ML illusion figures indicated the presence of the ML illusory effect in 10 capuchin monkeys. These results suggest that Cebus might be a good model for the experimental study of schizophrenia.

Color vision discrimination in the capuchin monkey Cebus apella : evidence for trichromaticity

Primates display significant differences in color vision. The purpose of this study was to assess the ability of capuchin monkeys in discriminating chromatic and achromatic Munsell color chips through behavioral tests. The subjects were trained in a simple and reverse discrimination learning procedure. All subjects were capable of discriminations along five color categories investigated. The results are discussed in terms of the hypothesis of male dichromatism in New World monkeys, the role of color vision in adaptation to feeding ecology, as well as to aspects regarding primate evolution.

Biodistribution and biocompatibility of DMSA-stabilized maghemite magnetic nanoparticles in nonhuman primates (Cebus spp.)

AIM This work represents the first reported investigation on the effects of magnetic nanoparticles (MNPs) in nonhuman primates. Biodistribution, biocompatibility and nanotoxicity of maghemite nanoparticles stabilized with dimercaptosuccinic acid (DMSA) were accessed. MATERIALS & METHODS A control animal was used and three other animals were intravenously injected with DMSA-MNPs and euthanized 12 h, 30 and 90 days following administration. Extracted organs were processed by histological techniques. An additional animal was used to collect blood samples to complementarily assess biocompatibility 12 h, 7, 15, 30, 60 and 90 days after DMSA-MNP injection. RESULTS DMSA-MNPs were preferentially addressed to the lungs, liver and kidneys. Hematological and serum biochemical results corroborated histological findings, supporting DMSA-MNP biocompatibility while preserving both hepatic and renal normal activity. CONCLUSION DMSA-MNPs were preferentially distributed to the lung, liver and kidneys. Furthermore, DMSA-MNPs were considered biocompatible, supporting their application as a promising nanomaterial platform for future biomedical use.

Effects of intra-nasally administered testosterone on sexual proceptive behavior in female capuchin monkeys (Cebus apella)

Sexual dysfunction in the female has been associated with a decrease in androgen levels, which can be reversed by testosterone treatment, however, bearing the risk of adverse side effects. Nasally administered testosterone could be an effective method for androgenic treatment avoiding the first-pass intestinal and hepatic metabolism and side effects. Here we examined the effects of chronic intranasal administration of testosterone on sexual behavior in female capuchin monkeys (Cebus apella) that lived with male cohorts. During 8 days of baseline 10 females were observed for their sexual and non-sexual behavior without drug. They then received daily intranasal testosterone (0.24 mg per nostril, n=5 per group) or placebo gel for 5 days, followed by 5 days of wash out, followed by 5 days of daily intranasal application, whereby the animals that had received testosterone before, now received placebo and vice versa. Diverse sexual and non-sexual behaviors were scored. Blood samples were collected and analyzed for testosterone, estradiol, dihydrotestosterone and progesterone using EIAs. The results revealed an increase in sexual behavior (eyebrow raising, chest rubbing, courtship behavior, masturbation) in the females during testosterone treatment, which seemed to be prolonged even when testosterone treatment was discontinued. These behavioral results were accompanied by an increase in plasma testosterone levels. This study demonstrates the efficacy of testosterone in enhancing sexual behavior in female capuchin monkeys by means of intranasal application, which may be a useful alternative compared to other forms of administration.

EEG and autonomic responses during performance of matching and non-matching to sample working memory tasks with emotional content

Working memory (WM) is a memory system responsible for the temporary storage of information and its utilization in problem solving. The central executive is theorized as the controller of storage functions that support WM. Neurophysiological data suggest that electroencephalographic (EEG) theta and alpha oscillations in frontal and midline regions are involved in neural communication between the central executive and storage functions during WM performance. Emotion is known to modulate several memory systems, including WM, through central and peripheral pathways. However, the physiological effect (EEG; autonomic nervous activity) of emotion over WM are not well described. In this study we aimed to identify physiological responses related to emotional WM performance. EEG (21 channels), heart rate (HR), and galvanic skin response (GSR) recordings were obtained from 54 volunteers while performing delayed matching and non-matching to sample tasks (DMTS/DNMTS). Emotional and neutral pictures from the International Affective Picture System and geometric figures were used as stimuli. As expected, WM performance was accompanied by presence of theta (frontal and midline electrodes) and alpha power (parietal electrodes). Beta and gamma oscillations were concentrated in frontopolar and left temporal regions. The DNMTS task was accompanied by higher increases in beta power, HR, and GSR compared to the DMTS task. Correlation analyses showed a positive tendency for gamma in the Fp2 site, ratio of LF/HF and skin conductance in both tasks. The HR results indicate an inverse reaction related to parasympathetic and sympathetic nervous system during the performance of the tasks. Taken together, our results contribute to elucidate the complex interactions between central and autonomic nervous systems in the modulation of emotional WM tasks.