Caracterização comportamental e distribuição de neurônios inibitórios em um modelo animal de autismo induzido por ácido valpróico

Autism comprises a heterogeneous group of neurodevelopmental disorders that affects the brain maturation and produces sensorial, motor, language and social interaction deficits in early childhood. Several studies have shown a major involvement of genetic factors leading to a predisposition to autism, which are possibly affected by environmental modulators during embryonic and post-natal life. Recent studies in animal models indicate that alterations in epigenetic control during development can generate neuronal maturation disturbances and produce a hyper-excitable circuit, resulting in typical symptoms of autism. In the animal model of autism induced by valproic acid (VPA) during rat pregnancy, behavioral, electrophysiological and cellular alterations have been reported which can also be observed in patients with autism. However, only a few studies have correlated behavioral alterations with the supposed neuronal hyper-excitability in this model. The aim of this project was to generate an animal model of autism by pre-natal exposure to VPA and evaluate the early post-natal development and pre-puberal (PND30) behavior in the offspring. Furthermore, we quantified the parvalbumin-positive neuronal distribution in the medial prefrontal cortex and Purkinje cells in the cerebellum of VPA animals. Our results show that VPA treatment induced developmental alterations, which were observed in behavioral changes as compared to vehicle-treated controls. VPA animals showed clear behavioral abnormalities such as hyperlocomotion, prolonged stereotipies and reduced social interaction with an unfamiliar mate. Cellular quantification revealed a decrease in the number of parvalbumin-positive interneurons in the anterior cingulate cortex and in the prelimbic cortex of the mPFC, suggesting an excitatory/inhibitory unbalance in this animal model of autism. Moreover, we also observed that the neuronal reduction occurred mainly in the cortical layers II/III and V/VI. We did not detect any change in the density of Purkinje neurons in the Crus I region of the cerebellar cortex. Together, our results strengthens the face validity of the VPA model in rats and shed light on specific changes in the inhibitory circuitry of the prefrontal cortex in this autism model. Further studies should address the challenges to clarify particular electrophysiological correlates of the cellular alterations in order to better understand the behavioral dysfunctions

Revisitando o eletrocorticograma intra-operatório na epilepsia mesial do lobo temporal: relevância das oscilações de alta frequência

Epilepsies are neurological disorders characterized by recurrent and spontaneous seizures due to an abnormal electric activity in a brain network. The mesial temporal lobe epilepsy (MTLE) is the most prevalent type of epilepsy in adulthood, and it occurs frequently in association with hippocampal sclerosis. Unfortunately, not all patients benefit from pharmacological treatment (drug-resistant patients), and therefore become candidates for surgery, a procedure of high complexity and cost. Nowadays, the most common surgery is the anterior temporal lobectomy with selective amygdalohippocampectomy, a procedure standardized by anatomical markers. However, part of patients still present seizure after the procedure. Then, to increase the efficiency of this kind of procedure, it is fundamental to know the epileptic human brain in order to create new tools for auxiliary an individualized surgery procedure. The aim of this work was to identify and quantify the occurrence of epilepticform activity -such as interictal spikes (IS) and high frequency oscillations (HFO) - in electrocorticographic (ECoG) signals acutely recorded during the surgery procedure in drug-resistant patients with MTLE. The ECoG recording (32 channels at sample rate of 1 kHz) was performed in the surface of temporal lobe in three moments: without any cortical resection, after anterior temporal lobectomy and after amygdalohippocampectomy (mean duration of each record: 10 min; N = 17 patients; ethic approval #1038/03 in Research Ethic Committee of Federal University of São Paulo). The occurrence of IS and HFO was quantified automatically by MATLAB routines and validated manually. The events rate (number of events/channels) in each recording time was correlated with seizure control outcome. In 8 hours and 40 minutes of record, we identified 36,858 IS and 1.756 HFO. We observed that seizure-free outcome patients had more HFO rate before the resection than non-seizure free, however do not differentiate in relation of frequency, morphology and distribution of IS. The HFO rate in the first record was better than IS rate on prediction of seizure-free patients (IS: AUC = 57%, Sens = 70%, Spec = 71% vs HFO: AUC = 77%, Sens = 100%, Spec = 70%). We observed the same for the difference of the rate of pre and post-resection (IS: AUC = 54%, Sens = 60%, Spec = 71%; vs HFO: AUC = 84%, Sens = 100%, Spec = 80%). In this case, the algorithm identifies all seizure-free patients (N = 7) with two false positives. To conclude, we observed that the IS and HFO can be found in intra-operative ECoG record, despite the anesthesia and the short time of record. The possibility to classify the patients before any cortical resection suggest that ECoG can be important to decide the use of adjuvant pharmacological treatment or to change for tailored resection procedure. The mechanism responsible for this effect is still unknown, thus more studies are necessary to clarify the processes related to it

The influence of visual inter-hemispheric connections on spiking, assembly and LFP activities, and their phase relationship during figure-ground stimulation

Desde os descobrimentos pioneiros de Hubel e Wiesel acumulou-se uma vasta literatura descrevendo as respostas neuronais do córtex visual primário (V1) a diferentes estímulos visuais. Estes estímulos consistem principalmente em barras em movimento, pontos ou grades, que são úteis para explorar as respostas dentro do campo receptivo clássico (CRF do inglês classical receptive field) a características básicas dos estímulos visuais como a orientação, direção de movimento, contraste, entre outras. Entretanto, nas últimas duas décadas, tornou-se cada vez mais evidente que a atividade de neurônios em V1 pode ser modulada por estímulos fora do CRF. Desta forma, áreas visuais primárias poderiam estar envolvidas em funções visuais mais complexas como, por exemplo, a separação de um objeto ou figura do seu fundo (segregação figura-fundo) e assume-se que as conexões intrínsecas de longo alcance em V1, assim como as conexões de áreas visuais superiores, estão ativamente envolvidas neste processo. Sua possível função foi inferida a partir da análise das variações das respostas induzidas por um estímulo localizado fora do CRF de neurônios individuais. Mesmo sendo muito provável que estas conexões tenham também um impacto tanto na atividade conjunta de neurônios envolvidos no processamento da figura quanto no potencial de campo, estas questões permanecem pouco estudadas. Visando examinar a modulação do contexto visual nessas atividades, coletamos potenciais de ação e potenciais de campo em paralelo de até 48 eletrodos implantados na área visual primária de gatos anestesiados. Estimulamos com grades compostas e cenas naturais, focando-nos na atividade de neurônios cujo CRF estava situado na figura. Da mesma forma, visando examinar a influência das conexões laterais, o sinal proveniente da área visual isotópica e contralateral foi removido através da desativação reversível por resfriamento. Fizemos isso devido a: i) as conexões laterais intrínsecas não podem ser facilmente manipuladas sem afetar diretamente os sinais que estão sendo medidos, ii) as conexões inter-hemisféricas compartilham as principais características anatômicas com a rede lateral intrínseca e podem ser vistas como uma continuação funcional das mesmas entre os dois hemisférios e iii) o resfriamento desativa as conexões de forma causal e reversível, silenciando temporariamente seu sinal, permitindo conclusões diretas a respeito da sua contribuição. Nossos resultados demonstram que o mecanismo de segmentação figurafundo se reflete nas taxas de disparo de neurônios individuais, assim como na potência do potencial de campo e na relação entre sua fase e os padrões de disparo produzidos pela população. Além disso, as conexões laterais inter-hemisféricas modulam estas variáveis dependendo da estimulação feita fora do CRF. Observamos também uma influência deste circuito lateral na coerência entre potenciais de campo entre eletrodos distantes. Em conclusão, nossos resultados dão suporte à ideia de um mecanismo complexo de segmentação figura-fundo atuando desde as áreas visuais primárias em diferentes escalas de frequência. Esse mecanismo parece envolver grupos de neurônios ativos sincronicamente e dependentes da fase do potencial de campo. Nossos resultados também são compatíveis com a hipótese que conexões laterais de longo alcance também fazem parte deste mecanismo

Expressão de fos após pulso de escuro no núcleo pré- geniculado do tálamo do sagui (Callithrix jacchus)

The pregeniculate nucleus (PGN) of the primate s thalamus is an agglomerate neuronal having a cap shaped located dorsomedially to the main relay visual information to the cerebral cortex, the dorsal lateral geniculate nucleus (GLD). Several cytoarchitectonic, neurochemical and retinal projections studies have pointed PGN as a structure homologous to intergeniculate leaflet (IGL) of rodents. The IGL receives retinal terminals and appears to be involved in the integration of photic and non-photic information relaying them, through geniculo-hypothalamic tract (TGH), to the main circadian oscillator in mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus. Thus, the IGL participates in the control of the biological rhythm by modulating the activity of the SCN. Pharmacological and IGL injury studies conclude that it is critical in the processing of non-photic information which is transmitted to the SCN. Other studies have found that especially neurons immunoreactive to neuropeptide Y (NPY) respond to this type of stimulation, determined by its colocation with the FOS protein. Has not been determined if the PGN responds, expressing the FOS protein, to the non-photic stimulus nor the neurochemical nature of these cells. Thus, we apply a dark pulse in the specifics circadian phases and analyze the pattern of expression of FOS protein in PGN of the marmoset (Callithrix jacchus). We found that in all animals analyzed the FOS expression was higher in the experimental than in the control group. There was a higher expression of FOS when the dark pulse was applied during the subjective day between the groups. Still, a subregion of the PGN, known by immunoreactive to NPY, had a greater number of FOS-positive cells in relation to his other just close dorsal region. Our data corroborate the theory that the PGN and IGL are homologous structures that were anatomically modified during the evolutionary process, but kept its main neurochemical and functional characteristics. However, injury and hodological studies are still needed for a more accurate conclusion

Expressão de genes imediatos induzidos por vocalizações em sagüis-comuns (Callithrix jacchus)

Immediate-early genes (IEGs) expression has been widely used as a valuable tool to investigate brain areas activated by specific stimuli. Studies of natural vocalizations, specially in songbirds, have largely benefited from this tool. Here we used IEGs expression to investigate brain areas activated by the hearing of conspecific common marmoset (Callithrix jacchus) vocalizations and/or utterance of antiphonal vocalizations. Nine adult male common marmosets were housed in sound-attenuating cages. Six animals were stimulated with playbacks of freely recorded natural long distance vocalizations (phee calls and twitters; 45 min. total duration). Three of them vocalized in response (O/V group) and three did not (O/n group). The control group (C) was composed by the remaining animals, which neither heard the playbacks nor spontaneously vocalized. After one hour of the stimulation onset (or no stimulation, in the case of the C group), animals were perfused with 0,9% phosphate-saline buffer and 4% paraformaldehyde. The tissue was coronally sectioned at 20 micro meter in a cryostat and submitted to immunohistochemistry for the IEGs egr-1 and c-fos. Marked immunoreactivity was observed in the auditory cortex of O/V and O/n subjects and in the anterior cingulate cortex, the dorsomedial prefrontal cortex and the ventrolateral prefrontal cortex of O/V subjects. In this study, brain areas activated by vocalizations of common marmosets were investigated using IEGs expression for the first time. Our results with the egr-1 gene indicate that potential plastic phenomena occur in areas related to hearing and uttering conspecific vocalizations.

Centros rombencefálicos de processamento auditivo do sagui (Callithrix jacchus): uma análise citoarquitetônica e neuroquímica

The auditory system is composed by a set of relays from the outer ear to the cerebral cortex. In mammals, the central auditory system is composed by cochlear nuclei, superior olivary complex, inferior colliculus and medial geniculate body. In this study, the auditory rombencephalic centers, the cochlear nuclear complex and the superior olivary complex were evaluated from the cytoarchitecture and neurochemical aspects, thorough Nissl staining and immunohistochemical techniques to reveal specific neuron nuclear protein (NeuN), glutamate (Glu), glutamic acid decarboxilase (GAD), enkephalin (ENK), serotonin (5-HT), choline acetyltransferase (ChAT) and calcium-binding proteins calbindin (CB), calretinin (CR), and parvalbumin (PV). The common marmoset (Callithrix jacchus), a little native primate of the Brazilian atlantic forest was used as an experimental animal. As results, it was noted that the cochlear nuclear complex is composed by anteroventral, posteroventral and dorsal nuclei, and the superior olivary complex is constituted by the lateral and medial superior olivary nuclei and the trapezoid body nucleus. Glu, GAD, ENK, ChAT, CB, CR, PV-immunoreactive cells, fibers and terminals besides besides only 5-HT terminals were found unhomogeneously in all nuclei, of both complex. The emerging data are discussed in a comparative and functional context, and represent an important contribution to knowledge of the central auditory pathways in the common marmoset, and then in primates

O Núcleo genuíno lateral dorsal do tálamo do sagüi (callithrix jacchus): Pprojeção retiniana, caracterização citoarquitetônica e neuroquimica da principal estação visual primária.

The thalamus plays an important role in the sensorial processing information, in this particular case, the visual information. Several neuronal groups have been characterized as conductors and processors of important sensorial information to the cerebral cortex. The lateral geniculate complex is one to them, and appears as a group very studied once it is responsible, in almost all totality, for the processing of visual information. Among the nuclei that constitute the lateral geniculate complex we highlight the dorsal lateral geniculate nucleus of the thalamus (DLG), the main thalamic relay for the visual information. This nucleus is located rostral and lateral to medial geniculate nucleus and ventral to thalamic pulvinar nucleus in most of the mammals. In the primates humans and non-humans, it presents as a laminate structure, arranged in layers, when observed in coronal sections. The objective of this work was to do a mapping of the retinal projections and a citoarchictetonic and neurochemical characterization of DLG in the marmoset (Callithrix jacchus), a New World primate. The retinal projections were traced by anterograde transport of subunit b of cholera toxin (CTb), the citoarchicteture was described by Nissl method, and to neurochemical characterization immunohistochemicals technical were used to examine the main neurotransmitters and neuroatives substances present in this neural center. In DGL of marmoset thalamus, in coronal sections labeled by Nissl method, was possible to visualize the division of this nucleus in four layers divided in two portions: magnocellular and parvocellular. The retinal projections were present being visualized fibers and terminals immunorreactives to CTb (IR-CTb) in the DLG ipsilateral and contralateral. And through the immunohistochemicals techniques was observed that DLG contain cells, fibers and/or terminals immunoreactives against neuronal nuclear protein, subunits of AMPA 15 glutamate receptors (GluR1, GluR2/3, GluR4), choline acetyltransferase, serotonin, glutamic acid decarboxylase, binding calcium proteins (calbindin, parvalbumin and calretinin), vasopressin, vasoactive intestinal polypeptide, and an astrocyte protein, glial fibrillary acidic protein.

Expressão de zif268 no cérebro do lagarto Tropidurus Hispidus após exploração de um ambiente enriquecido.

In the present work, we investigated behavioral changes associated with the increase in Zif268 protein expression within telencephalic areas of the tropical lizard Tropidurus hispidus that correspond to the mammalian hippocampus (HC). We used 13 male individuals of this species, collected at the Federal Agrotechnical School of Rio Grande do Norte, under SISBIO license number 19561-1. Four animals had their brains removed and were submitted to a Western blot with antibodies for the Zif268 protein. The remaining animals were separated in two different groups: a control group (n=4) and an exploration group (n=5). Animals from the exploration group were exposed to an enriched environment with many sensory cues novel to them. Control group animals stayed in the environment they were already habituated to. After 90 min from the onset of exposure to the new environment, animals from both groups were submitted to intracardiac perfusion with fixative, and the brains were removed, cryoprotected and frozen. After that, brains were sectioned at 20 μm and the sections were subjected to immunohistochemistry for the Zif268 protein. We verified that the Zif268 protein is likely conserved in the brain of T. hispidus, which showed antigenicity for the antibody anti-Zif268 made in mammals. In animals from the exploration group, we detected an increase of the Zif268 protein in the Septum, Striatum, Dorsoventricular Area and in cortical areas corresponding to the HC. This increase was proportional to the amount of environmental exploration, with maximum positive correlation in the hippocampal subareas Medial Cortex (R = 0.94 and p = 0.004) and Dorsomedial Cortex (R = 0.92 and p = 0.006). The data corroborate the notion that the reptilian hippocampus, as well as the mammalian HC, plays an important role in spatial exploration.

Efeitos do tratamento com lítio na memória aversiva, comportamentos relacionados à ansiedade e depressão e na expressão de BDNF em ratos

Lithium (Li) is the first choice to treat bipolar disorder, a psychiatric illness characterized by mood oscillations between mania and depression. However, studies have demonstrated that this drug might influence mnemonic process due to its neuroprotector, antiapoptotic and neurogenic effects. The use of Li in the treatment of cognitive deficits caused by brain injury or neurodegenerative disorders have been widely studied, and this drug shows to be effective in preventing or even alleviating the memory impairment. The effects of Li on anxiety and depression are controversial and the relationship of the effects of lithium on memory, anxiety and depression remain unknown. In this context, this study aims to: evaluate the effects of acute and chronic administration of lithium carbonate in aversive memory and anxiety, simultaneously, using the plus maze discriminative avoidance task (PMDAT); test the antidepressant effect of the drug through the forced swimming test (FS) and analyze brainderived neurotrophic factor (BDNF) expression in structures related to memory and emotion. To evaluation of the acute effects, male Wistar rats were submitted to i.p. administration of lithium carbonate (50, 100 or 200 mg/kg) one hour before the training session (PMDAT) or lithium carbonate (50 or 100 mg/kg) one hour before the test session (FS). To evaluation of the chronic effects, the doses administered were 50 or 100 mg/kg or vehicle once a day for 21 days before the beginning of behavioral tasks (PMDAT and FS). Afterwards, the animals were euthanized and their brains removed and submitted to immunohistochemistry procedure to quantify BDNF. The animals that received acute treatment with 100 and 200 mg/kg of Li did not discriminated between the enclosed arms (aversive and non-aversive) in the training session of PMDAT, showing that these animal did not learned the task. This lack of discrimination was also observed in the test session, showing that the animals did not recall the aversive task. We also observed an increased exploration of the open arms of these same groups, indicating an anxiolytic effect. The same groups showed a reduction of locomotor activity, however, this effect does not seem to be related with the anxiolytic effect of the drug. Chronic treatment with Li did not promote alterations on learning or memory processes. Nevertheless, we observed a reduction of open arms exploration by animals treated with 50 mg/kg when compared to the other groups, showing an anxiogenic effect caused by this dose. This effect it is not related to locomotor alterations since there were no alterations in these parameters. Both acute and chronic treatment were ineffective in the FS. Chronic treatment with lithium was not able to modify BDNF expression in hippocampus, amygdala and pre-frontal cortex. These results suggest that acute administration of lithium promote impairments on learning in an aversive task, blocking the occurrence of memory consolidation and retrieval. The reduction of anxiety following acute treatment may have prevented the learning of the aversive task, as it has been found that optimum levels of anxiety are necessary for the occurrence of learning with emotional context. With continued, treatment the animals recover the ability to learn and recall the task. Indeed, they do not show differences in relation to control group, and the lack of alterations on BDNF expression corroborates this result. Possibly, the regimen of treatment used was not able to promote cognitive improvement. Li showed acute anxiolytic effect, however chronic administration 4 promoted the opposite effect. More studies are necessary to clarify the potential beneficial effect of Li on aversive memory

Sistema de agentes poligínicos para esteganálise de imagens digitais

In this work, we propose a multi agent system for digital image steganalysis, based on the poliginic bees model. Such approach aims to solve the problem of automatic steganalysis for digital media, with a case study on digital images. The system architecture was designed not only to detect if a file is suspicious of covering a hidden message, as well to extract the hidden message or information regarding it. Several experiments were performed whose results confirm a substantial enhancement (from 67% to 82% success rate) by using the multi-agent approach, fact not observed in traditional systems. An ongoing application using the technique is the detection of anomalies in digital data produced by sensors that capture brain emissions in little animals. The detection of such anomalies can be used to prove theories and evidences of imagery completion during sleep provided by the brain in visual cortex areas

Medida de uma codificação de estímulos sonoros por potenciais pós-sinápticos e potenciais de campo local usando teoria da informação

Coding process is a fundamental aspect of cerebral functioning. The sensory stimuli transformation in neurophysiological responses has been a research theme in several areas of Neuroscience. One of the most used ways to measure a neural code e ciency is by the use of Information Theory measures, such as mutual information. Using these tools, recent studies show that in the auditory cortex both local eld potentials (LFPs) and action potential spiking times code information about sound stimuli. However, there are no studies applying Information Theory tools to investigate the e ciency of codes that use postsynaptics potentials (PSPs), alone and associated with LFP analysis. These signals are related in the sense that LFPs are partly created by joint action of several PSPs. The present dissertation reports information measures between PSP and LFP responses obtained in the primary auditory cortex of anaesthetized rats and auditory stimuli of distinct frequencies. Our results show that PSP responses hold information about sound stimuli in comparable levels and even greater than LFP responses. We have also found that PSPs and LFPs code sound information independently, since the joint analysis of these signals did neither show synergy nor redundancy.

Modelo animal da Doença de Parkinson baseado na expressão de alfa - sinucleína: caracterização comportamental, eletrofisiológica e avaliação dos efei tos da estimulação da medula espinhal

Parkinson disease (PD) is associated with motor symptoms and dopaminergic cell loss in the nigrostriatal pathway. Alpha-synuclein is the major component of the Lewy bodies, the biological hallmarks of disease, and has been associated with familial cases of PD. Recently, the spinal cord stimulation (SCS) showed to be effective to alleviate the Parkinson symptoms in animal models and human patients. In this project, we characterized the motor and electrophysiological effects of alpha-synuclein overexpression in the substantia nigra of rats. We further investigated the effects of spinal electrical stimulation, AMPT and L-dopa administration in this model. Method: Sprague-Dawley rats were injected with empty viral vector or the vector carrying the gene for alpha-synuclein in the substantia nigra, and were tested weekly for 10 weeks in the open field and cylinder tests. A separated group of animals implanted with bilateral electrode arrays in the motor cortex and the striatum were recorded in the open field, during the SCS sessions and the pharmacological experiments. Results: Alpha-synuclein expression resulted in motor asymmetry, observed as the reduction in use of contralateral forepaw in the cylinder test. Animals showed an increase of local field potential activity in beta band three and four weeks after the virus injection, that was not evident after the 5th week. AMPT resulted in a sever parkinsonian state, with reduction in the locomotor activity and significant peak of oscillatory activity in cortex and striatum. SCS was effective to alleviate the motor asymmetry at long term, but did not reduce the corticostriatal low frequency oscillations observed 24 hs after the AMPT administration. These oscillations were attenuated by L-dopa that, even as SCS, was not effective to restore the locomotor activity during the severe dopaminergic depletion period. Discussion: The alpha-synuclein model reproduces the motor impairment and the progressive neurodegenerative process of PD. We demonstrated, by the first time, that this model also presents the increase in low frequency oscillatory activity in the corticostriatal circuit, compatible with parkinsonian condition; and that SCS has a therapeutic effect on motor symptom of this model.

Caracterização de células de lugar no hipocampo e de suas relações com oscilações do potencial de campo local

The main inputs to the hippocampus arise from the entorhinal cortex (EC) and form a loop involving the dentate gyrus, CA3 and CA1 hippocampal subfields and then back to EC. Since the discovery that the hippocampus is involved in memory formation in the 50's, this region and its circuitry have been extensively studied. Beyond memory, the hippocampus has also been found to play an important role in spatial navigation. In rats and mice, place cells show a close relation between firing rate and the animal position in a restricted area of the environment, the so-called place field. The firing of place cells peaks at the center of the place field and decreases when the animal moves away from it, suggesting the existence of a rate code for space. Nevertheless, many have described the emergence of hippocampal network oscillations of multiple frequencies depending on behavioral state, which are believed to be important for temporal coding. In particular, theta oscillations (5-12 Hz) exhibit a spatio-temporal relation with place cells known as phase precession, in which place cells consistently change the theta phase of spiking as the animal traverses the place field. Moreover, current theories state that CA1, the main output stream of the hippocampus, would interplay inputs from EC and CA3 through network oscillations of different frequencies, namely high gamma (60-100 Hz; HG) and low gamma (30-50 Hz; LG), respectively, which tend to be nested in different phases of the theta cycle. In the present dissertation we use a freely available online dataset to make extensive computational analyses aimed at reproducing classical and recent results about the activity of place cells in the hippocampus of freely moving rats. In particular, we revisit the debate of whether phase precession is due to changes in firing frequency or space alone, and conclude that the phenomenon cannot be explained by either factor independently but by their joint influence. We also perform novel analyses investigating further characteristics of place cells in relation to network oscillations. We show that the strength of theta modulation of spikes only marginally affects the spatial information content of place cells, while the mean spiking theta phase has no influence on spatial information. Further analyses reveal that place cells are also modulated by theta when they fire outside the place field. Moreover, we find that the firing of place cells within the theta cycle is modulated by HG and LG amplitude in both CA1 and EC, matching cross-frequency coupling results found at the local field potential level. Additionally, the phase-amplitude coupling in CA1 associated with spikes inside the place field is characterized by amplitude modulation in the 40-80 Hz range. We conclude that place cell firing is embedded in large network states reflected in local field potential oscillations and suggest that their activity might be seen as a dynamic state rather than a fixed property of the cell.

Efeito agudo da respiração abdominal lenta sobre a atividade cerebral, respostas emocionais e cardiovasculares

Introduction: Slow abdominal breathing (SAB) stimulates baroreflex and generates respiratory sinus arrhythmia, changing cardiovascular, emotional and cerebral systems acute and chronically. However, although meditative practices have been receiving increasingly attention in the last years, there is no agreement on the neurophysiological changes underlying them, mainly because of the lack of topographical pieces of information. Purpose: We aimed to analyze the acute effect of SAB on brain activity, emotional and cardiovascular responses in untrained subjects in meditative techniques. Methods: Seventeen healthy adults’ men were assessed into two different sessions in a random and crossed order. Into experimental session, they breathed in 6 cycles/minute and in control session they kept breathing in normal rate, both for 20 minutes. xi Before, during, and after each session we assessed brain activity using electroencephalography (EEG), anxiety, mood, heart rate variability (HRV) and blood pressure. The sLORETA software was used to analyze EEG data for source localization of brain areas in which activity was changed. Results: The sLORETA showed that beta band frequency was reduced in frontal gyrus (P<0.01) and anterior cingulate cortex (P<0.05) both during and after SAB (P<0.05) compared to the moment before it. There was no change in brain activity in control session. Additionally, a two-way repeated measures ANOVA showed that there was no effect on anxiety (P>0.8) and mood (P>0.08). There were improvements in HRV (P<0.03), with increased RR interval and decreased HR after SAB, as well as increased SDNN, RMSSD, pNN50, low frequency, LF/HF ratio, and total power during it, with no changes in SBP and DBP. Conclusions: We conclude that SAB is able to change brain activity in areas responsible for emotional processing, even without behavioral changes. Furthermore, SAB improves HRV and does not change blood pressure in normotensive.

Modulaçao do estresse social sobre parâmetros fisiológicos, comportamentais, cognitivos e plasticidade neuronal em saguis (Callithrix jacchus) juvenis: um modelo psiquiátrico e cognitivo

Nos períodos críticos de plasticidade neural ocorre uma maior permissividade do sistema nervoso ao ambiente, por isto, a ação do estresse sobre o individuo e suas repercussões sobre áreas responsáveis pelo controle dos sistemas de resposta ao estresse e por funções cognitivas complexas vem recebendo bastante atenção. A utilização de modelos experimentais translacionais tem sido imprescindível na elucidação destes mecanismos e das patologias associadas. Diante disto, este trabalho investigou os efeitos do estresse social sobre parâmetros fisiológicos, comportamentais, cognitivos e sobre a neurogênese no córtex pré-frontal (CPF) durante um período crítico de plasticidade cerebral, a fase juvenil, em machos de Callithrix jacchus. Durante cinco meses, 5 animais foram acompanhados em suas famílias (GF) e 5 animais foram isolados socialmente por 4 meses (GI), após um mês em observação em ambiente familiar (fase basal- FB). Ao final do 5º mês foram aplicados 2 testes de memória de trabalho (MT) nos animais GF e GI. Em seguida, 3 animais de cada grupo foram sacrificados para análise do fator de neurogênese BDNF ( Brain Derived Neurotrophic Factor) por imunofluorescência no CPF (sub-regiões orbitofrontal e lateral). Os animais do GF não variaram significativamente o cortisol ao longo do estudo, enquanto o GI elevou o cortisol e comportamentos indicadores de ansiedade (CA) na primeira semana do isolamento. Em seguida, o GI apresentou uma redução no cortisol, nos CA, no peso corporal e um aumento de comportamentos estereotipados e da anedonia, alterações tipicamente depressivas em primatas não-humanos. Ao final, o GI apresentaram níveis de cortisol menores que em FB. Ambos os grupos apresentaram dificuldades em realizar e aprender as tarefas cognitivas e a presença de BDNF no córtex pré-frontal foi independente do grupo (GF ou GI), porém correlacionou-se com os níveis de cortisol presentes na ultima semana do estudo, e os animais com presença de BDNF no CPF lateral e orbitofrontal apresentaram maiores níveis de cortisol. Estes resultados contribuem no processo de validação do sagui como um bom modelo psiquiátrico translacional e aponta para possibilidade de estudos sobre transtornos depressivos na juventude e suas repercussões posteriores. Além disto, os resultados observados para as tarefas cognitivas levou-nos a fazer uma releitura dos protocolos utilizados em estudos de memoria de trabalho com animais adultos desta espécie, com a finalidade de aprimora-los facilitando a aprendizagem em animais juvenis, naives e em situações de estresse. Ademais, evidenciou-se pela primeira vez a relação do estresse, cortisol e níveis de BDNF, em animais juvenis desta espécie, com a fim de contribuir com sua utilização como modelo animal neurocognitivo.