PPGNEURO - Mestrado em Neurociências
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Master Thesis Investigação da dinâmica longitudinal da vocalização de saguis (Callithrix jacchus)(Universidade Federal do Rio Grande do Norte, 2025-01-20) Carvalho, Ricardo José Viana de; Takahashi, Daniel Yasumasa; http://lattes.cnpq.br/4659230362946311; http://lattes.cnpq.br/8029687909883036; Silva, Adelaide Hercília Pescatori; https://orcid.org/0000-0001-5569-6621; http://lattes.cnpq.br/2441898800354402; Souza, Arrilton Araújo de; http://lattes.cnpq.br/8822052460371633There are currently around 7,000 languages spoken around the world, many of which are so distinct that efficient communication between different groups is impossible. The massive migration of individuals, the occupation of varied ecological niches, geographical isolation between communities, vocal plasticity and prosociality are considered fundamental factors for linguistic diversity in humanity. If this hypothesis is correct, we might expect that other species exhibiting similar characteristics would also show a diversity in communication structure, i.e. have dialects. Marmosets (Callithrix jacchus) have explored different ecological niches, demonstrate vocal plasticity and are among the few primate species recognized for their pro-sociability. In this project, we investigated possible vocal differences between two wild groups of marmosets (Callithrix jacchus), called Água and Bosque, which are free-living animals in the Açú National Forest and do not interact with each other. We used passive acoustic recording methods, with recorders attached to resting and sleeping trees, minimizing direct interaction with the animals and allowing us to capture vocalizations over the course of a year. Our data show that temperature influences the duration of the groups' vocalizations throughout the year, the seasons and the day, so that at higher temperatures, the animals decrease the duration of their vocalizations, adopting an energy conservation strategy. However, when comparing the duration of vocalizations between the groups, there was no statistically significant difference throughout the year, nor between the dry and rainy seasons. Thus, it can be concluded that the two groups of marmosets (Callithrix jacchus) show vocal similarities, resulting in similar vocalizations during the year.Master Thesis Comparação de padrões de conectividade cerebral em esquizofrenia e estados induzidos por ayahuasca através de rs-fMRI(2025-12-01) Silva, Alex Sandro da; Araújo, Dráulio Barros de; https://orcid.org/0000-0002-6934-2485; http://lattes.cnpq.br/7818012155694188; https://orcid.org/0000-0001-6330-3883; http://lattes.cnpq.br/8457006164870374; Sanders, Lia Lira Olivier; https://orcid.org/0000-0002-3823-9821; http://lattes.cnpq.br/9755275761805348; Ribeiro, Sidarta Tollendal Gomes; https://orcid.org/0000-0001-9325-9545; http://lattes.cnpq.br/0649912135067700Due to the phenomenological similarity between psychotic symptoms and the effects produced by classic psychedelics, the first clinical models proposed for schizophrenia were based on the effects of these substances. Although this relationship has been discussed in the literature for over a century, a consensus has only emerged in the last two decades that the effects caused by classic psychedelics and psychotic symptoms do not exhibit strong functional or structural equivalence. However, a history of psychiatric illness or previous psychotic symptomatology still constitutes a key exclusion criterion in clinical trials involving psychedelics. Given that most comparisons between the effects of psychedelics and the symptoms of schizophrenia have been performed indirectly in the literature, the central objective of this work was to directly compare the neural dynamics observed in schizophrenia and in states induced by ayahuasca, a preparation rich in N,N-dimethyltryptamine (DMT). To this end, we investigated patterns of resting-state functional brain connectivity (rs-fMRI) in four groups: healthy volunteers (n = 19), patients with schizophrenia (n = 18), and healthy volunteers under the acute (n = 9) and subacute (n = 21) effects of ayahuasca. Functional connectivity was estimated using an ROI-to-ROI approach (Harvard–Oxford atlas), with correlations transformed into Fisher’s Z scores. Group differences were assessed using general linear models (ANOVA and t-tests), controlling for sex and applying false discovery rate correction for multiple comparisons (p-FDR). Complementary analyses included the assessment of similarity between connectivity patterns using Tucker’s congruence coefficient, dimensionality reduction via principal component analysis (PCA), and integration with physiological markers using regression models. The results revealed that both schizophrenia and the acute ayahuasca state are characterized by alterations in thalamo-cortical communication and connectivity within the Default Mode Network (DMN). Compared to healthy volunteers, patients with schizophrenia exhibited thalamo-cortical hyperconnectivity (involving temporal, sensorimotor, and occipital regions) and hypoconnectivity within the DMN, as well as between the occipital, somatosensory, and temporal cortices. Similarly, subjects in the acute ayahuasca state displayed thalamo-cortical hyperconnectivity (encompassing auditory and somatosensory areas), hypoconnectivity in the DMN, and increased interhemispheric limbic connectivity. Congruence analysis confirmed several similarities, including thalamo-temporal/somatosensory hyperconnectivity and hypoconnectivity in the DMN. Crucial differences were, however, observed: the thalamo-cortical hyperconnectivity under the acute effect of ayahuasca was more restricted to the superior temporal cortex, while in schizophrenia it appeared more diffuse, associated with regions exhibiting reduced functional integration. Furthermore, schizophrenia showed decreased fronto-temporal connectivity, in contrast to the enhanced integration observed during the acute ayahuasca state. Our work underscores the necessity of expanding theoretical models, such as the cortico-striato-thalamo-cortical (CSTC) circuit applied to schizophrenia, to incorporate structural and physiological alterations, as well as the chronic nature of this condition.Master Thesis Impacto dos canabinoides na cognição, humor, sono e na qualidade de vida em pacientes longevos com diagnóstico de síndrome demencial leve a moderada(Universidade Federal do Rio Grande do Norte, 2025-08-04) Mello Neto, Pedro da Costa; Ribeiro, Sidarta Tollendal Gomes; Araújo, Draulio Barros de; https://orcid.org/0000-0002-6934-2485; http://lattes.cnpq.br/7818012155694188; http://lattes.cnpq.br/0649912135067700; http://lattes.cnpq.br/1426800960591102; Queiroz, Cláudio Marcos Teixeira de; http://lattes.cnpq.br/3384801391828521; Menezes, João Ricardo; Reis, Marina PáduaLife expectancy and consequently, the number of dementia cases has increased globally, demanding new therapeutic approaches. Tetrahydrocannabinol (THC) and cannabidiol (CBD), cannabinoids derived from Cannabis sativa, exhibit neuroprotective properties and modulate mood and sleep. This non-randomized descriptive, quantitative, and longitudinal study evaluated the impact of Cannabis sativa formulations rich in CBD and THC on cognition, mood, sleep, and quality of life in 19 elderly patients diagnosed with mild to moderate dementia of various etiologies. Dosages were individually adjusted under medical supervision. Participants were assessed using validated psychometric scales before the initiation of treatment and after four months. The results indicated significant improvement in neuropsychiatric symptoms, quality of life, and life satisfaction. Appropriate statistical tests were applied based on data distribution, with corrections for multiple comparisons and canonical correlation analysis. The findings support the hypothesis of the safety and therapeutic potential of cannabinoid use in elderly patients with dementia in an outpatient setting. Despite these promising results, large-scale clinical trials with more rigorous methodologies and expanded scientific criteria are essential to validate these preliminary findings and establish more precise and evidence-based therapeutic guidelines for clinical practice.Master Thesis Correlatos psicofisiológicos e sociais da Síndrome de Burnout em estudantes do ensino médio de duas escolas públicas de Natal-RN(Universidade Federal do Rio Grande do Norte, 2025-07-14) Cavalcanti Neto, Geraldo Bezerra; Sousa, Maria Bernardete Cordeiro de; http://lattes.cnpq.br/8488760386226790; http://lattes.cnpq.br/4751138427903064; Barbosa, Silvânia da Cruz; https://orcid.org/0000-0003-0435-0801; http://lattes.cnpq.br/2486108351700966; Moreira, Simone da Nóbrega Tomaz; http://lattes.cnpq.br/3642294168997314Adolescence is a critical phase of human development, marked by rapid physical and behavioral transformations, as well as increased vulnerability to social and cultural challenges. In this context, the family and school environments play essential roles in the socialization process and in supporting young people's well-being. As a result, various initiatives have been implemented globally to develop programs and public policies aimed at promoting mental health among adolescents, particularly high school students. This study aimed to investigate the biopsychosocial conditions of high school students in order to identify potential associations between psychophysiological and pathophysiological variables and school burnout syndrome. The research was conducted in two of the most traditional full-time public high schools in the city of Natal, Brazil, with a sample composed of 95 students from the 1st (n = 50) and 3rd (n = 45) years of high school. To assess burnout, sociodemographic data were collected, along with psychometric instruments measuring empathy, school satisfaction (relationships with teachers and peers), family support, and salivary cortisol as a physiological marker. High scores in the emotional exhaustion and cynicism dimensions were observed in 88.4% and 68.4% of the students, respectively, while 41.1% showed low professional efficacy. Statiscal analysis of the R language presents results that show that 28.4% of the students presented signs of burnout syndrome, characterized by high scores in emotional exhaustion and cynicism and, simultaneously, low professional efficacy. The analysis of school burnout showed that the "cynicism" subdomain had a significant positive effect (β = 0.749), whereas professional efficacy had a significant negative effect (β = -0.369; p = 0.012). Regarding empathy, 1% of the students were classified as having low empathy, while the majority were classified as moderately empathetic (72%) or empathetic (27%). High scores were observed in the dimensions of perspective-taking (66.3%), interpersonal flexibility (18.9%), altruism (33.7%), and affective sensitivity (75.8%). However, the total score of the effect of empathy on burnout was not statistically significant. In terms of family support, low or moderately low perceptions were observed in the subdomains of consistent emotional support (77.9%), family adaptability (71.6%), and autonomy (71.6%). In the school environment, most students reported high or moderate satisfaction with their teachers (91.6%) and peers (73.2%). The variable "sex" showed no significant differences in burnout prevalence. The structural equation modeling analysis indicated that family support had a significantly negative and moderate effect on burnout (β = -0.63; p < 0.0001). Third-year students showed significantly higher cortisol levels, which were associated with higher levels of emotional exhaustion, a core subdomain of burnout. The main findings highlight the crucial role of family support in students' school well-being and reveal that higher cortisol levels are associated with burnout in the final year of high school. These findings underscore the need for targeted interventions involving both parents and students to mitigate burnout and promote well-being, thereby supporting student retention in the school environment.Master Thesis Investigação da expressão de egr-1 nos gânglios da base durante a produção e percepção vocal em Callithrix jacchus(Universidade Federal do Rio Grande do Norte, 2024-06-17) Sá, Anna Gabriely Barroso de; Takahashi, Daniel Yasumasa; http://lattes.cnpq.br/4659230362946311; http://lattes.cnpq.br/3496180687690450; Schmidt, Kerstin Erika; Ribeiro, Sidarta Tollendal Gomes; Lima, Bruss Rebouças Coelho; Simões, Cristiano SoaresA fundamental aspect of human communication is flexible speech, which has long been believed to be exclusive to humans among primates. However, recent findings suggest that some non-human primates, such as marmosets, also exhibit vocal plasticity. Investigating the neural correlates of vocal flexibility in marmosets may provide insight into its origins in humans due to brain homologies. Among the brain areas related to vocal behavior, much is known about cortical contributions, but the function of subcortical regions is much less known. In particular, the basal ganglia are related to the choice/initiation of actions, fine motor control and the learning of motor sequences; therefore, it is likely that they are relevant to vocal flexibility. Here, using previously collected histological data and stereological methods, we tested the hypothesis that the caudate nucleus and putamen in the basal ganglia are activated during vocal communication and used the expression of the immediate early gene egr-1 to map their activation in three groups of marmosets. The first group did not vocalize during the test (C), the second group heard playback vocalizations but did not vocalize (H/O), and the third group heard playback calls and vocalized (H/V). We observed an increase in erg-1 expression in both areas in the H/O condition compared to the C condition and an even more significant increase in erg-1 expression in the same areas in the H/V condition compared to the H/O condition. To ensure the specificity of the changes observed, we compared the cells expressing erg-1 in the primary sensory and motor areas, finding no significant difference between the three conditions. In addition, we quantified locomotion during the hour before the end point of the experiment to rule out movement discrepancies as an explanation for the differences observed between the groups in erg-1 expression, without finding a correlation between locomotion and expression variation. Our results indicate activation of the basal ganglia during hearing and vocalization production, independently of other brain areas and body movements, which corroborates our hypothesis. The relevance of the basal ganglia in vocal learning in songbirds, together with our findings in marmosets, suggests their importance in understanding the evolution of vocal learning.Master Thesis Avaliação dos efeitos do canabigerol e do canabinol nas crises agudas induzidas pelo pentilenotetrazol em camundongos(Universidade Federal do Rio Grande do Norte, 2024-06-21) Lamartine, Adriana Freire; Takahashi, Daniel Yasumasa; http://lattes.cnpq.br/4659230362946311; http://lattes.cnpq.br/9243894383609211; Sequerra, Eduardo Bouth; Menezes, João RicardoPhytocannabinoids, secondary metabolites produced by Cannabis plants, modulate cellular excitability and present promising effects in adjunctive treatment for refractory epilepsies. Tetrahydrocannabinol (THC) and cannabidiol (CBD), two phytocannabinoids with the highest concentration in Cannabis sp. inflorescences, have similar mass and molecular structure, but distinct pharmacological effects: THC has a clear psychotropic and pro-convulsant effect, while CBD does not affect behavior or perception, despite notable anti-seizure activity in clinical and preclinical studies. On the other hand, little is known about the pharmacological effects of other phytocannabinoids, such as cannabigerol (CBG, a precursor molecule of THC and CBD) and cannabinol (CBN, which results from the abiotic degradation of THC and CBD). CBG and CBN interact with different molecular targets, such as receptors of the endocannabinoid system (CB1r), but their pharmacological effects on neuronal hyperexcitability are unknown. In this study, we evaluated the antiseizure effect of CBG and CBN in a model of chemically-induced acute seizures by pentylenetetrazol (PTZ) in mice (CEUA/UFRN #043/2022). PTZ administration (60 mg/kg, s.c.) produced spasms, myoclonic jerks, and in some animals, generalized limbic seizures. Pretreatment (1 h before PTZ) with CBG or CBN at doses of 3, 30, or 300 mg/kg (i.p.) did not modify the latency, quantity, or severity of PTZ-induced ictal behaviors compared to the control group (CTR, animals receiving vehicle, i.e., corn oil; p>0.05, ANOVA). On the other hand, pretreatment with diazepam (5 mg/kg, a traditional anti-seizure drug, used here as positive control) increased the latency to the first spasm and the first myoclonus and significantly reduced the number of events compared to the control group (p<0.05, unpaired t-test). Surprisingly, the pretreatment with CBG or CBN increased the proportion of animals experiencing limbic seizures, regardless of the dose. The proportion of animals with seizures in the CTR group was 2/16 (13%), while in the CBG group, it was 8/17 (47%, CTR vs CBG, chi-square=4.66, p=0.031) and in the CBN group it was 5/16 (31%, CTR vs CBN, chi-square=1.65, p>0.05). Our results demonstrate that CBG and CBN do not have antiseizure activity in the PTZ-induced acute seizure model and suggest that these phytocannabinoids promote the expression of limbic seizures. We believe this study expands our understanding of the potential and limitations of the endocannabinoid system in controlling neuronal excitability.Master Thesis Efeito da excentricidade na frequência das oscilações gama de V1 em capuchinhos(Universidade Federal do Rio Grande do Norte, 2024-03-28) Silva, Thais Priscila Lima; Neuenschwander, Sérgio; https://orcid.org/0000-0001-7493-121X; http://lattes.cnpq.br/9217956361436464; http://lattes.cnpq.br/6395496858042816; Rohenkohl, Gustavo; Baron, Jerome Paul Armand Laurent; Schmidt, Kerstin ErikaThe frequency of oscillation is crucial for synchronizing (and breaking) neuronal synchronization. In this study, we recorded spike activity at locations corresponding to distinct points in the visual map of V1 in Capuchin Monkeys (N= 195 recording sites in 3 monkeys). Our results confirm and deepen previous findings in Resos (Lima et al., 2010, limited to LFP recordings), showing that gamma oscillation frequency is systematically higher in the central representation (mean 66.3 Hz ± 2.09 SEM) compared to the peripheral representation of the visual field (51.9 Hz ± 1.98). In our study, we were able to record both in the foveal representation (1°) and in the far periphery to measure the effects on oscillation frequency when cortical magnification was higher, systematically varying stimulus properties (moving gratings) such as orientation, speed, spatial frequency, and size. Our results offer an alternative interpretation to the findings of Murty et al. (J. Neurosci, 2018), which suggest the existence of two distinct gamma rhythms in V1, depending on the size of the stimulus. Low-frequency components originating in the periphery of V1 (calcarine, slow gamma) could propagate to the central representation region (operculum, fast gamma) through volume conduction. As we discuss in this work, the two gamma rhythms should be conceived not as playing a complementary role in visual processing but as a mere epiphenomenon of the topological arrangement of the underlying cortical circuit.Master Thesis Estudo comportamental e eletroencefalográfico do desempenho da tarefa Go/No-Go ao longo do ciclo menstrual(Universidade Federal do Rio Grande do Norte, 2023-12-04) Lima, Luana Adalice Borges de Araújo; Sousa, Maria Bernardete Cordeiro de; Souza, Rafaela Faustino Lacerda de; http://lattes.cnpq.br/8488760386226790; http://lattes.cnpq.br/1794031731087670; Araújo, Draulio Barros de; https://orcid.org/0000-0002-6934-2485; http://lattes.cnpq.br/7818012155694188; Campos, Tânia FernandesMotor behavior involves the adaptive control of movement and depends on mechanisms arising from perception and cognition that plan and execute different complex movement actions of an innate nature acquired through learning. Steroid hormones, in turn, act as transcription factors participating in signaling pathways and modulation of neural functions, including motor function. Evidence shows that sex steroids influence neurotransmission in the central nervous system, affecting the quality of female performance in motor tasks, highlighting the importance of restriction and motor control in human behavior. The present study investigated whether cortical activity and variations related to skeletal muscle activity present changes in the phases of the menstrual cycle (menstrual, follicular and luteal) in 30 women during a Go/NoGo Protocol. This test included pairs of auditory stimuli (1st stimulus = S1; 2nd stimulus = S2) that were grouped into two general types: centered on S1 and centered on S2. In the S1-centered task, the decision is made after S1 and motor execution/inhibition occurs after S2. In tasks centered on S2, decision making and execution occur only after S2. Cortical activity was recorded using electroencephalography (EEG) in the medial frontal regions (Fz), left center (C3) and center-right (C4) to study specifically the alpha (8-13Hz), beta (15-30Hz) and beta 1 (15-23Hz) rhythms. The relationships between these EEG measures and Go/No-Go behavioral outcomes and ERPs were assessed. Through the Friedman test, behavioral activity significantly differed in reaction time and accuracy between the S1 and S2 centered protocols, but without significant differences regarding menstrual cycle phases. A moderate positive correlation was found between reaction time and progesterone levels in protocol centered on S1. Changes in brain activity with the generation of beta-ERS during movement initiation in the medial frontal region suggest an increase in motor stimulus control associated with the decreased levels of HSFs found in the menstrual phase. Furthermore, beta and alpha oscillations in the left central region were significantly more pronounced in the follicular and luteal phases, suggesting a modulation resulting from the increase in sex hormones, estradiol and progesterone, in the processing and execution of motor tasks. In summary, this pioneering study highlights variations in motor cognition throughout the menstrual cycle in Go/No-Go tasks, which may have implications for optimizing motor performance of women during the reproductive age, providing an important basis for future research and clinical approaches.Master Thesis Papel da PKA cortical na formação da memória de reconhecimento de objetos(Universidade Federal do Rio Grande do Norte, 2023-09-28) Araújo, Raquel Lúcia Souto de; Cammarota, Martin Pablo; Rossato, Janine Inez; https://orcid.org/0000-0002-7980-5842; http://lattes.cnpq.br/8136970112250481; https://orcid.org/0000-0001-9741-5074; http://lattes.cnpq.br/4888317387600937; http://lattes.cnpq.br/0623474419062785; Laplagne, Diego Andres; Gonzalez, Maria CarolinaRecognition memory is a central component of declarative memories. Failures in the processing of these memories lead to severe consequences that characterize the initial symptoms in patients with cognitive decline, such as Alzheimer's disease. The novel object recognition task is used to evaluate the molecular mechanisms involved in the processing of recognition memory which requires the detection of novelty in the environment. Different regions of the brain are required to discriminate objects. The medial prefrontal cortex (mPFC) and the hippocampus play distinct roles during the processing of this type of memory. Dopamine is important for novelty detection and signaling mediated by the activation of D1/D5 receptors is mediated by cAMP-activated protein kinase, PKA. The aim of this study was to evaluate the role of cortical PKA in the formation of object recognition memory in rats. Adult and middle-aged male and female Wistar rats were bilaterally implanted with cannulas in the mPFC. Our results show that, in rats, the consolidation of long-term object recognition memory requires PKA activation in the mPFC shortly after training. Sex, age and time of the light/dark cycle do not interfere with formation of this type of memory and PKA inhibition in these individuals also induces amnesia. PKA inhibition also prevents short-term object recognition memory formation. With these findings we can infer that PKA in the mPFC is essential for object recognition memory formation.Master Thesis Exposição intra-amniótica ao ácido valpróico induz teratogênese e reproduz endofenótipo dos modelos animais de autismo(Universidade Federal do Rio Grande do Norte, 2023-02-28) Real, Ana Luíza Campos Vila; Pereira, Rodrigo Neves Romcy; http://lattes.cnpq.br/9209418339421588; http://lattes.cnpq.br/9090119100629090; Bloise, Enrrico; Anomal, Renata Figueiredo; http://lattes.cnpq.br/6437989445919424Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that includes, approximately, 1% of the world’s population. ASD is characterized by clinical observations of deficits in social communication and interaction and, also, the prevalence of repetitive behaviors and restricted interests. Currently, several animal models are used to investigate the neurobiological mechanisms associated with ASD. The animal model generated by exposing rats, during pregnancy, to valproic acid (VPA) is already well established in the literature. The effect of VPA exposure in rats is similar to what is observed in the clinic: the use of this drug during pregnancy increases the prevalence of children born with the autistic phenotype. The evaluation of several studies about this model indicates that the behavioral phenotype of these animals is expressed differently, depending on the dose used, the route of administration and the stage of development in which the exposure occurs. Therefore, in this study, we sought to investigate the effects of exposure to VPA administered via the intra-amniotic route (VPAia), directly in rat fetuses, at doses of 2.0 and 2.5 μmoles. For this, we performed a medial laparotomy in pregnant rats, on the 12th gestational day, for exposure of the uterine horns and subsequent microinjections of VPAia. This administration was given during the stage of development when neural tube closure occurs, and in which the exposure to VPA is associated with autistic phenotypes in the offspring and the development of neural tube defects. The hypotheses of this work were (1) that exposure to VPAia would induce autistic-like behavioral phenotypes in the offspring; (2) that the severity of these phenotypes would be dose-dependent; and (3) that behavioral phenotypes would be expressed more homogenously compared to the model induced by intraperitoneal VPA administration. Once the injections were done, we followed the births and developmental milestones of the pups during the first few postnatal weeks. We evaluated weight, time for eye opening, recorded their ultrasonic vocal production during maternal separation and applied behavioral tests of social interaction. Our results show that the doses used (2.0 and 2.5 μmol/fetus) induced teratogenicity in less than 10% of the injected animals. Analyzes of weight and eye-opening time did not reveal developmental changes in VPAia animals compared to control animals. As for the vocalizations, the VPAia animals vocalized less than the controls at the age of 7 days (P7; p<0.05), without significant alterations at P14 and P21. We also observed less exploratory activity in the open field apparatus (P21; p<0.005), shorter time spent walking in the center of the open field apparatus (P30; p<0.05) and a greater number of entries at the social interaction zone (ZIS; P35; p<0.05) of VPAia animals. We can conclude, therefore, that the administration of VPAia promoted changes in some characteristic behaviors of animal models of ASD, such as vocalization and locomotor activity, but without significant effects on stereotypes and social interaction.Master Thesis Efeitos eletrofisiológicos do sevoflurano em neurônios piramidais da camada 5 do córtex auditivo primário do camundongo(Universidade Federal do Rio Grande do Norte, 2023-05-15) Araújo, Aelton Silva; Leão, Emelie Katarina Svahn; https://orcid.org/0000-0001-7295-1233; http://lattes.cnpq.br/1279823352935722; https://orcid.org/0000-0001-5960-996X; http://lattes.cnpq.br/6864851885074431; Takahashi, Daniel Yasumasa; http://lattes.cnpq.br/4659230362946311; Leão, Ricardo Maurício XavierGeneral anesthetics are ubiquitous in medical practice, but the cellular mechanisms that promote amnesia, analgesia, immobility and unconsciousness by modulating voltage- and ligand-gated ion channels are still poorly understood. Recent studies are beginning to show the diversity of different anesthetics in regulating specific ion channels and that cortical pyramidal neurons are affected by lower concentrations than interneurons. This highlights that general anesthesia does not follow a "general" mechanism but depends on the choice of anesthetics with cell-type specific effects that need to be studied case by case. For example, the electrophysiological effects of volatile anesthetics such as sevoflurane are especially hard to study in in vitro preparations, yet, biophysical models predict stabilization of the open-state of low-threshold voltage-gated K+ channels (Kv1.2). Here we attempt a first step in identifying the electrophysiological profile of sevoflurane on layer 5 pyramidal neurons (L5 PNs) of the auditory cortex of adult mice. We applied sevoflurane by passing the carbogen mixture through a vaporizer for volatile anesthetic thereby both oxygenating and solubilizing sevoflurane in the artificial cerebrospinal fluid (aCSF) used for whole-cell patch-clamp recordings. The concentration of sevoflurane in the aCSF was quantified using gas chromatography-mass spectrometry. We further subdivided L5 PN into type A and B cells based on responses to small depolarizing and hyperpolarizing current steps, since type A and type B L5 PNs display subtle differences in membrane properties that might be modulated by sevoflurane. Quantification of passive and active membrane properties before and after application of low dose sevoflurane (approximately 22 µM) showed a decrease in the firing frequency for both cell types and a specific effect of depolarizing the action potential threshold of type A PNs, (APthreshold aCSF: -36.31 ± 0.94 mV; sevo: -21.75 ± 4.39 mV; p = 0.009; n = 8 cells) and increasing the action potential half-width of type B PNs (APHalf-width aCSF: 1.80 ± 0.13 ms; sevo: 2.29 ± 0.23 ms; p = 0.040; n = 10). Stable recordings after the washout of sevoflurane restored partially initial maximum firing frequency, AP threshold for type A and AP half-width for type B L5 PNs. Our preliminary results conclude that sevoflurane decreases the firing frequency of both types of L5 PNs, however, membrane properties are differentially affected depending on cell type. This work shows for the first time the direct effect of sevoflurane on L5 cortical pyramidal cells and adds to the cellular understanding of the mechanism of action of volatile anesthetics.Master Thesis Sono e aprendizagem em Octopus insularis(Universidade Federal do Rio Grande do Norte, 2023-01-30) Paiva, Mizziara Marlen Matias de; Ribeiro, Sidarta Tollendal Gomes; http://lattes.cnpq.br/0649912135067700; http://lattes.cnpq.br/8384422489387376; Marian, José Eduardo Amoroso Rodriguez; Sequerra, Eduardo Bouth; http://lattes.cnpq.br/2028204211415978; Leite, Tatiana SilvaAmong invertebrate animals, the class of cephalopods has stood out in research for its remarkable intelligence and learning ability. In particular, octopuses have shown complex behavior regarding the organization of their nervous system, which includes a lobe for learning. These animals also show, as already known in vertebrates, learning skills by touch and observation. In the literature, there are studies carried out with the species O. vulgaris in which it was verified that octopuses are able to change behavior based on the results of experiments, demonstrating that they can associate information and reproduce adaptive behavioral responses. Sleep is a behavior that occurs in several taxa of the animal kingdom and has already been extensively studied in vertebrates, especially in mammals and birds. However, among invertebrates, in the case of octopuses, there are behavioral and electrophysiological studies that point to the existence of at least two sleep phases. Among the objectives of this study, we seek to relate the learning capacity of these animals with the quiet and active sleep patterns, as well as to investigate and describe in detail, through a comprehensive behavioral quantification, a learning process in the species Octopus insularis. In order to do that, we submitted the animals to a task called “Russian Dolls”. Using video recordings, we are assessing whether the young adults of this species are capable of learning a new task, which requires the animals to sequentially open up to three different jars, one inside the other, one smaller than the other, with a reward (crab or shrimp) inside the smaller jar. We observed that the octopuses are able to open the 3 types of jars, often opening each of them in many different ways, which shows the cognitive ability and behavioral versatility of these animals, showing a significant value to the bigger jar step. Regarding the sleep monitoring, it was observed that the learning task caused changes in the duration of the active sleep episodes before and after the task.Master Thesis Ritmos respiratórios no bulbo olfatório e córtex pré-frontal medial durante o comportamento do tipo ansioso(Universidade Federal do Rio Grande do Norte, 2023-02-27) Dias, Ana Luiza Alves; Tort, Adriano Bretanha Lopes; Laplagne, Diego Andres; https://orcid.org/0000-0001-5860-1667; http://lattes.cnpq.br/0293416967746987; https://orcid.org/0000-0002-9877-7816; http://lattes.cnpq.br/3181888189086405; http://lattes.cnpq.br/3451581806806030; Barbosa, Flávio Freitas; Teixeira, Robson SchefferAnxiety is characterized as a state of perception of threats that can lead to danger. It is considered an evolutionarily adaptive behavior that results in different physiological changes. The emotional response evoked by anxiety causes activation of brain areas and temporal coordination of neuromodulation. Over the past 20 years, studies have shown that changes in the activity of the hippocampus, amygdala, and prefrontal cortex (PFC) would be related to fear and anxiety responses. The connections between these areas are thought to be coordinated by the theta oscillations (~ 6 - 12 Hz). However, recent findings have shown that a larger network could be related to the modulation of anxiety, which would be orchestrated by the projections from the olfactory bulb (OB) to the PFC. Namely, both the OB and PFC exhibit neuronal oscillations that synchronize to the phase of the respiratory cycle and are named respiratory rhythms (RR) because of their co-variability in peak frequency with the breathing rate. These refer to actual LFP oscillations coupled with breathing and not the mechanical process of breathing itself. Lower LFP frequencies present themselves as a mechanism for long-range communication through the synchronization of cortical brain regions during different behavioral states, which could be the case of RR. In this work, we wanted to understand how the changes in the respiratory cycle could influence the appearance of these oscillations and how they could be related to the behavioral state during anxiety. For that, we recorded respiration through intranasal pressure and LFPs from the medial PFC (anterior cingulate, prelimbic and medial orbital), OB and parietal cortex of 7 male Wistar rats as they freely behaved in the elevated plus maze (EPM). We found that the respiratory rate changes depending on the behavioral state (anxious vs non-anxious) and locomotor activity. Furthermore, changes in the LFP power spectrum also depend on the behavioral state and reflect changes in respiratory activity. Finally, we observed RR in the same frequency range as theta during more anxious states. We hypothesize that the theta rhythm described in previous anxiety studies may have been confused with RR, and that this rhythm may coordinate longrange communication in the brain, being found both in the frontal brain and in more distant regions such as the parietal cortex.Master Thesis Avaliação da resposta imune materna contra alvos no cérebro fetal durante a origem de microcefalias derivadas da infecção pelo vírus zika(Universidade Federal do Rio Grande do Norte, 2022-11-21) Maia, Sara do Nascimento; Sequerra, Eduardo Bouth; Jerônimo, Selma Maria Bezerra; http://lattes.cnpq.br/2028204211415978; http://lattes.cnpq.br/7520226696373251; Maranhão, Andréa Queiroz; Leao, Emelie Katarina SvahnDuring pregnancy, the mother's immune system undergoes several physiological changes that induce its tolerance to the cells of the embryo. As the embryo has half the genome of its father, the breach of tolerance can induce the production of maternal antibodies against fetal antigens. Among the variables that can induce the breakdown of tolerance are infections by pathogens. Congenital Zika virus (ZIKV) infection leads to malformation of the central nervous system (CNS) in most cases, which has been called congenital Zika virus syndrome (SCZ). In some cases, the patient is born without any clear sequelae and develops postnatal microcephaly, which suggests persistent inflammation of the CNS. Thus, in this project we tested the hypothesis that in addition to the direct damage caused by the viral infection, patients may experience a maternal autoimmune response. Here we show that mothers of children with SCZ have higher levels of antibodies against Engrailed1, a protein expressed by the developing hindbrain. The level of antibodies against Engrailed 1 correlates with the level of ZIKV antibody expression that each mother expresses. However, levels of antibodies against Engrailed 1 do not correlate with the occurrence of epilepsies or hindbrain malformations. We further tested whether serum from mothers of SCZ children reacts with slices of adult hippocampus or telencephalon from rodent embryos, a method employed to detect neural autoantibodies. Serum from these patients does not react against these tissues or even against organoid slices from human brains. Thus, this work suggests that ZIKV infection during pregnancy stimulates the production of maternal antibodies against a target expressed in the embryonic CNS. However, this production does not reflect on the severity of the case, which is probably more dependent on direct infection by the virus.Master Thesis Efeitos da paroxetina durante sessões de teste e reteste no labirinto em cruz elevado(Universidade Federal do Rio Grande do Norte, 2022-06-30) Paiva, Izabela Lima; Tort, Adriano Bretanha Lopes; https://orcid.org/0000-0002-9877-7816; http://lattes.cnpq.br/3181888189086405; http://lattes.cnpq.br/2087840828035036; Barbosa, Flavio Freitas; Belchior, Hindiael Aeraf; https://orcid.org/0000-0002-6898-3985; http://lattes.cnpq.br/2815729240392635Anxiety and fear mediate critical fight-and-flight responses, which are essential to survival. As a pathology, anxiety is characterized by the overvaluation of potential threats and sustained worry. Such a condition strongly impacts daily life, resulting in a social dysfunction that can trigger other mood disorders such as depression and bipolar disorder. According to a World Health Organization estimative, anxiety disorders affect around 3.6% of the world population, and this number increased drastically after the COVID-19 pandemic. The elevated plus-maze (EPM) is the most used task for assessing anxiety-like behavior in rodents. This task is based on an avoidance-approach conflict generated by the natural behavior of rodents to explore a new environment and its aversion to open and light spaces. Interestingly, when the animals are re-exposed to the maze, a phenomenon called one-trial tolerance (OTT) may occur. In this phenomenon, drugs that have an anxiolytic effect when administered on the first day of EPM exposure tend not to be anxiolytic when administered on the second day. Of note, OTT has implications for translatability from preclinical research since the EPM is often used as an acute task during screening for anxiety treatments. In the present study, we investigated the effects of the systemic administration of paroxetine, a selective serotonin reuptake inhibition widely used to treat anxiety disorders, during a test (first exposure) and a retest (second exposure) session in the EPM taking place in consecutive days. Given that anxiety disorders exhibit gender differences since they are more prevalent in females, we studied cohorts of both male and female C57BL/J6 mice, which were analyzed either combined or separately. Our results show that paroxetine is indeed anxiolytic during the test session in the EPM. Nevertheless, we observed the OTT phenomenon in animals treated with vehicle in the test session and with paroxetine 24 hours later in the retest session, in which case paroxetine no longer had an anxiolytic effect. Curiously, we also found that paroxetine treatment in the first EPM session leads to a long-term anxiolytic effect; namely, animals later injected with vehicle in the retest session exhibited a lower anxietylike behavioral profile than animals treated with vehicle in both the test and retest sessions. Further experimental protocols revealed that paroxetine administered after the first EPM exposure was also associated with a long-term anxiolytic effect in the second EPM exposure 24 hours later. Most of our results held true when analyzing males and females separately, though specific sex differences in some behaviors could also be found. In all, we conclude that paroxetine has different effects during the test and retest sessions in the EPM.Master Thesis Decaimento da frequência gama: estudo comparativo entre a retina, o núcleo geniculado lateral e o córtex(Universidade Federal do Rio Grande do Norte, 2018-12-14) Silva, Luana Dantas da; Maciel, Sérgio Tulio Neuenschwander; Schmidt, Kerstin Erika; Baron, Jerome Paul Armand LaurentGamma oscillations (30 to 90 Hz) has been implicated in cognitive processes such as visual binding (Singer, 1999; Uhlhaas et al., 2009) and attention (Fries, 2001; Gregoriou et al. Pesaran et al., 2002; Montgomery and Buzsáki, 2007; Lima et al., 2011). The communication through coherence hypothesis (CTC), proposed by Pascal Fries (Fries, 2005; Fries, 2009), identifies gamma as a key mechanism for stimulus encoding and control of the flow of information in cortical-cortical systems. Accordingly, experimental work on monkeys has suggested that the modulation of oscillation frequency may be fundamental for establishing coherence, and hence neural communication, for example between cortical areas V1 - V4, and V1 - V2 (Bosman et al, 2012; Roberts et al., 2013). Indeed, non-matching frequencies can be used as distinct channels for information transmission, as suggested between FEF and V4 (Gregoriou et al., 2009) and the hippocampus and the entorhinal cortex (Colgin et al, 2009). Thus, the oscillation frequency is likely a critical parameter for the modulation of gamma oscillations during attentional control. On the other hand, it is also known that gamma frequency depends on stimulus features, such as velocity (Gray et al., 1990; Lima et al., 2010); size (Gieselmann and Thiele, 2008), orientation and contrast (Ray & Mausell, 2015). The eccentricity position in the visual map seems as well determinant for the oscillation frequency, as higher frequencies are systematically seen for receptive fields at the central representation of the visual field as compared to the peripheral representation. Interestingly, gamma frequency is rarely stationary along the course of the responses. In general, oscillation frequency decreases continuously in the first hundreds of milliseconds after stimulus onset. This is a robust phenomenon, observable at different levels of the visual system, for a variety of species (cats, monkeys, humans, mice; see examples in CasteloBranco et al., 1998; Neuenschwander et al., 1999; Van Pelt et al., 2012; Storchi et al., 2017). Although remarkable, this decay in gamma frequency has been mostly ignored, and a possible functional role remains evasive (Fries et al., 2015). Here, we characterize the decay of gamma frequency for a variety of stimulus conditions. Comparisons are made for two systems known to show strong gamma oscillations: (1) the retinogeniculate system of the cat and (2) the primary visual cortex of the monkey. A robust finding is that both the retina and the cortex show pronounced decay in gamma frequency. This is striking since the cortical oscillations are known independent of the rhythms originated in the retina (CasteloBranco et al., 1998; Saleem et al., 2017). Overall, gamma frequency decay was observed for a variety of stimuli and appeared to be independent of the instantaneous firing of the cells. We discuss the possible meaning of a decay in frequency for the current ideas of the role of gamma in stimulus encoding and attentional control.Master Thesis Spike-field coherence in the low-gamma band of the primary visual cortex of agouti and cats(Universidade Federal do Rio Grande do Norte, 2021-10-01) Moura, Júlio Cesar da Costa; Schmidt, Kerstin Erika; Maciel, Sergio Tulio Neuenschwander; Baron, Jerome Paul Armand LaurentMaster Thesis Ripples e fast ripples na epileptogênese: caracterização das oscilações de alta frequência após o estado epiléptico(Universidade Federal do Rio Grande do Norte, 2021-07-30) Rocha, Antonio Jhones Lima da; Queiroz, Claudio Marcos Teixeira de; Aguiar, Cleiton Lopes; Calganotto, Maria ElisaHigh-frequency oscillations (HFOs) are spontaneous (80-500 Hz), transient and fast (20-100 ms) oscillations observed in cortical structures in mammals. Recorded mainly during slow-wave sleep (SWS) and quiet waking, physiological HFOs (ripples, between 80 and 200 Hz) participate in sensorial perception and memory consolidation. In parallel, pathological HFOs (above 200 Hz) occur in brain regions involved in the seizure initiation in individuals with epilepsy. In this work, we used electrophysiological recordings and an animal model of status epilepticus (SE) to study the expression of HFOs associated with epileptogenesis in mice. Animals were implanted with deep electrodes, bilaterally, in the hippocampus and retrosplenial cortex. We also implanted a guide-cannula in the right dorsal hippocampus for local administration of pilocarpine. After the recording of the sleep-wake cycle (baseline; minimum of 2 days, 5 h/day), animals received a single intrahippocampal dose of pilocarpine (560 µg/site in 800 nL) for the induction of status epilepticus (SE) during video-electrophysiology recordings. After SE, animals were recorded in four moments in time: one day after SE (SE+1), two days after SE (SE+2), between 7-14 days after SE (SE+7) and between 15 and 30 days (SE+30). The recordings were processed to identify ripples and pathological HFOs in windows of slow wave sleep and during the two initial hours of the SE, respectively. We identified 1,689 ripples in 6 animals. We observed that ripple rate of occurrence decreased after SE (F[4,20]=4.34, p=0.01; ANOVA), as well as oscillation frequency of ripples (F[4,20]=5.39, p=0.003; ANOVA). We did not identify statistical differences regarding power and duration of ripples after the SE. Interestingly, we observed a significant correlation between the reduction in frequency of ripples and the severity of the SE (SE+2, R= -0.82, p= 0.05; Spearman), as well as between the rate of ripples and the severity of the SE (SE+2, R= -0.94, p= 0.01; Spearman). As to the pathological HFOs, we did not identify a single oscillation above 200 Hz in the baseline period. Curiously, pathological HFOs were detected in the first seconds of the first seizure of the SE in all recorded animals (N=6). Similar events were detected on day SE+1 in two animals. Most of the pathological HFOs occurred coupled with high-amplitude ictal spikes. The pathological HFOs showed higher oscillation frequency (t(38)=-8.8, p< 0.001), power (t(38)=-15.5, p< 0.001) and duration (t(38)=-4.6, p< 0.001, testes t de Welch), when compared to ripples. As far as we know, this work is the first study to extensively describe the evolution of the electrophysiological profile of ripples during epileptogenesis. Our results show that ripple alterations are partially explained by SE severity. We also show that pathological HFOs occur in the first seconds after the beginning of SE, suggesting that these oscillations do not need structural reorganization for its expression. Our hypothesis is that pathological HFOs result from a sustained depolarization of a neuronal population which recurrent (feedback) inhibition is functional, contributing with synchronized firing of action potentials in a neuronal population. Taken together, we observed that ripples and pathological HFOs display distinct dynamics, during and after the SE, that can help to comprehend the temporal evolution of epilepsy.Master Thesis Effect of Cannabis extract on noise induced tinnitus and anxiety-related behaviour in adolescent mice(Universidade Federal do Rio Grande do Norte, 2021-07-15) Paixão, Rodolfo Diógenes da; Leão, Emelie Katarina Svahn; http://lattes.cnpq.br/1279823352935722; http://lattes.cnpq.br/4988018421366299; Queiroz, Cláudio Marcos Teixeira de; http://lattes.cnpq.br/3384801391828521; Barbosa, Flávio Freitas; http://lattes.cnpq.br/3611261597113820Tinnitus is an auditory condition characterised as phantom sounds, often described as ringing or hissing sounds. Chronic bothersome tinnitus can lead to stress, anxiety and even depression, and still lacks standardized treatments. Recently Cannabis has gathered attention as it might modulate both behaviour and synaptic activity acting in the endocannabinoid system. However, literature is still inconclusive about beneficial or detrimental effects of Cannabis treatment for tinnitus. Here we used a model of noiseinduced tinnitus to investigate, first, if tinnitus is altered by a low dose Cannabis extract rich in tetrahydrocannabinol (extract, 2.44 mg/kg; THC, 1.0 mg/kg); second, if noiseexposure is related to increased anxiety and, third, if tinnitus-related anxiety is affected by Cannabis administration. We used gap prepulse inhibition of the acoustic startle (GPIAS) to assess tinnitus perception, and the open field (OF) and elevated plus maze (EPM), to evaluate anxiety behaviour. Our results show that only a subgroup of noiseexposed mice developed tinnitus-like behaviour (noise-exposed Tinnitus-like, and noiseexposed Not tinnitus-like) and that GPIAS index was not altered by Cannabis treatment in either group. When investigating anxiety-like behaviour we found noise-exposed mice to show reduced centre entries in the OF test 30 minutes after Cannabis extract administration compared to vehicle (p = 0.007) and reduced locomotion compared to sham (p = 0.042). In the EPM, noise-exposed mice entered fewer times into the closed arms compared to sham animals (p = 0.026). After Cannabis administration noiseexposed animals entered fewer times into the open arms of the EPM (p = 0.003). Subdivision of noise-exposed mice revealed, in the OF, that tinnitus-like mice entered less the centre after Cannabis administration compared to vehicle (p = 0.022). In the EPM, tinnitus-like and not tinnitus-like mice showed reduced entries in closed arms and open arms, respectively (tinnitus-like, p = 0.0167; not tinnitus-like, p = 0.033). Also, tinnitus-like mice spent more time in closed arms after Cannabis administration (p = 0.021). Thereby, specifically noise-exposed mice with tinnitus-like behaviour avoided the OF centre area and preferred to stay inside the closed arms of the EPM after cannabis administration. In summary this work shows that anxiety tests can be an addition to GPIAS tests to evaluate tinnitus and potential therapeutic substances. Future studies will test lower doses of cannabis extract for anxiolytic effects in treating tinnitus-related stress and anxiety.Master Thesis Experiências auditivas na juventude alteram a discriminação auditiva no Mandarim-Diamante (Taeniopygia guttata)(Universidade Federal do Rio Grande do Norte, 2021-03-25) Barbalho, Gabriela Peixoto; Velho, Tarciso André Ferreira; ; http://lattes.cnpq.br/8194534389725093; ; http://lattes.cnpq.br/7907565884329843; Pichorim, Mauro; ; http://lattes.cnpq.br/5696697654544552; Figuerola, Wilfredo Blanco; ; http://lattes.cnpq.br/9912829629195282Songbirds are considered one of the best animal models to investigate the neurobiological basis of vocal learning. As in humans, these animals have distinct phases for vocal learning that are influenced by social and motor experiences. More specifically, social deprivation in songbirds can generate deficits in the individual's vocal production, whereas singing prevention delays vocal maturation. However, it is not completely clear whether limited experience during development can affect the animal's auditory discrimination abilities, a well-known phenomenon in humans. To address this question, we manipulate social and motor practice experiences in zebra finches, the most widely used songbird species. We first confirmed that our manipulation altered vocal learning, without grossly affecting development. More precisely, socially deprived animals showed abnormal songs, typical of animals lacking a song model. In contrast, juvenile animals where singing practice was limited continued to produce immature vocalizations as adults. Notably, behavioral experiments demonstrated that control animals, i.e., animals with normal social experiences, showed a lower performance in auditory discrimination tasks compared to isolated and juvenile animals. Conversely, sing-limited did not differ from control birds. These results suggest that early development auditory experiences may influence the discriminatory capacity in adult zebra finches, while vocal practice appears to have little influence in the performance of adult birds. That is, birds that are exposed to normal social experiences during postnatal development may have diminished ability to discriminate conspecific songs. Such interpretation is in agreement with the increased specificity observed in auditory neurons, and would parallel the perceptual losses observed during speech acquisition in humans.