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1.
Elife ; 92020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32955014

RESUMO

Social aggression and avoidance are defensive behaviors expressed by territorial animals in a manner appropriate to spatial context and experience. The ventromedial hypothalamus controls both social aggression and avoidance, suggesting that it may encode a general internal state of threat modulated by space and experience. Here, we show that neurons in the mouse ventromedial hypothalamus are activated both by the presence of a social threat as well as by a chamber where social defeat previously occurred. Moreover, under conditions where the animal could move freely between a home and defeat chamber, firing activity emerged that predicted the animal's position, demonstrating the dynamic encoding of spatial context in the hypothalamus. Finally, we found that social defeat induced a functional reorganization of neural activity as optogenetic activation could elicit avoidance after, but not before social defeat. These findings reveal how the hypothalamus dynamically encodes spatial and sensory cues to drive social behaviors.


Assuntos
Agressão/fisiologia , Hipotálamo , Comportamento Espacial/fisiologia , Animais , Hipotálamo/citologia , Hipotálamo/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Optogenética
2.
Biol Rev Camb Philos Soc ; 95(4): 889-910, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32097520

RESUMO

Mixed-species animal groups (MSGs) are widely acknowledged to increase predator avoidance and foraging efficiency, among other benefits, and thereby increase participants' fitness. Diversity in MSG composition ranges from two to 70 species of very similar or completely different phenotypes. Yet consistency in organization is also observable in that one or a few species usually have disproportionate importance for MSG formation and/or maintenance. We propose a two-dimensional framework for understanding this diversity and consistency, concentrating on the types of interactions possible between two individuals, usually of different species. One axis represents the similarity of benefit types traded between the individuals, while the second axis expresses asymmetry in the relative amount of benefits/costs accrued. Considering benefit types, one extreme represents the case of single-species groups wherein all individuals obtain the same supplementary, group-size-related benefits, and the other extreme comprises associations of very different, but complementary species (e.g. one partner creates access to food while the other provides vigilance). The relevance of social information and the matching of activities (e.g. speed of movement) are highest for relationships on the supplementary side of this axis, but so is competition; relationships between species will occur at points along this gradient where the benefits outweigh the costs. Considering benefit amounts given or received, extreme asymmetry occurs when one species is exclusively a benefit provider and the other a benefit user. Within this parameter space, some MSG systems are constrained to one kind of interaction, such as shoals of fish of similar species or leader-follower interactions in fish and other taxa. Other MSGs, such as terrestrial bird flocks, can simultaneously include a variety of supplementary and complementary interactions. We review the benefits that species obtain across the diversity of MSG types, and argue that the degree and nature of asymmetry between benefit providers and users should be measured and not just assumed. We then discuss evolutionary shifts in MSG types, focusing on drivers towards similarity in group composition, and selection on benefit providers to enhance the benefits they can receive from other species. Finally, we conclude by considering how individual and collective behaviour in MSGs may influence both the structure and processes of communities.


Assuntos
Comportamento Animal/fisiologia , Biodiversidade , Aves/classificação , Peixes/classificação , Mamíferos/classificação , Répteis/classificação , Animais , Técnicas de Observação do Comportamento , Evolução Biológica , Aves/fisiologia , Ingestão de Alimentos/fisiologia , Comportamento Alimentar/fisiologia , Peixes/fisiologia , Mamíferos/fisiologia , Comportamento Predatório/fisiologia , Répteis/fisiologia , Comportamento Espacial/fisiologia , Fatores de Tempo
3.
Behav Neurosci ; 133(6): 602-613, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31580093

RESUMO

Previous results suggest that directional information from the head direction cell circuit may inform hippocampal place cell firing when an animal is confronted with visually identical environments. To investigate whether such information might also be essential for spatial behavior, we tested adult, male Lister Hooded rats that had received either bilateral lateral mammillary nuclei (LMN) lesions or sham lesions on a four-way, conditional odor-location discrimination in compartments arranged at 60° to one another. We found that significantly fewer rats in the LMN lesion group were able to learn the task compared to the Sham group. We also found that the extent of the behavioral impairment was highly correlated with the degree of tissue loss in the LMN resulting from the lesion. Animals with LMN lesions were also impaired in a nonmatching-to-sample task in a T maze, and the extent of impairment likewise depended on the extent of the lesion. Performance in the odor-location and T-maze tasks was not affected by tissue loss in the medial mammillary nuclei. Together, these results indicate that the LMN, a key node in the head direction circuit, is critical for solving a spatial task that requires a directional discrimination. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Assuntos
Comportamento Espacial/fisiologia , Processamento Espacial/fisiologia , Potenciais de Ação , Animais , Cabeça/fisiologia , Masculino , Corpos Mamilares/lesões , Corpos Mamilares/fisiopatologia , Vias Neurais/fisiologia , Neurônios/metabolismo , Neurônios/fisiologia , Ratos , Ratos Endogâmicos , Tálamo/lesões
4.
Psychopharmacology (Berl) ; 236(9): 2847-2854, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31069423

RESUMO

RATIONALE: Cognitive decline and dementia are major concerns in today's aging society. As limited treatments are available, measures to prevent cognitive decline and dementia are needed. We previously demonstrated that matured hop bitter acids (MHBA), bitter components of beer, increase norepinephrine in the hippocampus and improve memory in amnesia model mice induced by scopolamine (SCP), an antagonist of muscarinic receptor. However, other neurotransmitters involved in the effects of MHBA on memory improvement remain unknown. OBJECTIVES: This study aimed to assess the role of acetylcholine receptors (AChR) in the effects of MHBA on memory. METHOD: The involvement of AChR on the effects of MHBA (10 mg/kg) on cognitive function was evaluated using AChR antagonists, SCP, mecamylamine hydrochloride (MEC), a non-competitive antagonist of nicotinic-AChR (nAChR), and methyllycaconitine citrate (MLA), an α7nAChR antagonist, for the Y-maze test and the novel object recognition test (NORT). A separate population of mice, which underwent vagotomy or sham operation, was subjected to NORT to elucidate further mechanism. In addition, the effect of MHBA on acetylcholinesterase (AChE) activity was measured in vitro. RESULTS: In accordance with previous reports, MHBA improved spontaneous alternations of the Y-maze test in SCP-induced amnesia mice and increased discrimination index evaluated by the NORT in normal mice. On the other hand, treatment with MEC or MLA attenuated the effects of MHBA on memory improvement in the Y-maze test and the NORT. Vagotomized mice also showed attenuated memory enhancement by MHBA in the NORT. In addition, MHBA did not alter AChE activity in vitro. CONCLUSIONS: The results support the involvement of nAChRs in memory improvement in mice by MHBA. MHBA is thus thought to activate the vagal nerve and enhance hippocampus-dependent memory via nAChRs.


Assuntos
Humulus , Memória/efeitos dos fármacos , Extratos Vegetais/farmacologia , Receptores Nicotínicos/metabolismo , Reconhecimento Psicológico/efeitos dos fármacos , Comportamento Espacial/efeitos dos fármacos , Animais , Cognição/efeitos dos fármacos , Cognição/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Memória/fisiologia , Camundongos , Camundongos Endogâmicos ICR , Antagonistas Muscarínicos/farmacologia , Antagonistas Nicotínicos/farmacologia , Extratos Vegetais/isolamento & purificação , Reconhecimento Psicológico/fisiologia , Comportamento Espacial/fisiologia
5.
Neuropharmacology ; 144: 327-336, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30439418

RESUMO

Tobacco smoke is the leading preventable cause of death in the world and treatments aimed to increase success rate in smoking cessation by reducing nicotine dependence are sought. Activation of peroxisome proliferator-activated receptor-alpha (PPARα) by synthetic or endogenous agonists was shown to suppress nicotine-induced activation of mesolimbic dopamine system, one of the major neurobiological substrates of nicotine dependence, and nicotine-seeking behavior in rats and monkeys. An alternative indirect way to activate PPARα is inhibition of N-acylethanolamine acid amidase (NAAA), one of the major hydrolyzing enzyme for its endogenous agonists palmitoylethanolamide (PEA) and oleoylethanolamide (OEA). We synthetized a novel specific brain permeable NAAA inhibitor, AM11095. We administered AM11095 to rats and carried out brain lipid analysis, a functional observational battery (FOB) to assess toxicity, in vivo electrophysiological recording from dopamine cells in the ventral tegmental area, brain microdialysis in the nucleus accumbens shell and behavioral experiments to assess its effect on nicotine -induced conditioned place preference (CPP). AM11095 (5 and 25 mg/kg, i.p.) was devoid of neurotoxic and behavioral effects and did not affect motor behavior and coordination. This NAAA inhibitor (5 mg/kg i.p.) increased OEA and PEA levels in the hippocampus and cortex, prevented nicotine-induced activation of mesolimbic dopamine neurons in the ventral tegmental area, nicotine-induced elevation of dopamine levels in the nucleus accumbens shell and decreased the expression of nicotine CPP. Our results indicate that NAAA inhibitors represent a new class of pharmacological tools to modulate brain PEA/PPARα signalling and show potential in the treatment of nicotine dependence.


Assuntos
Amidoidrolases/antagonistas & inibidores , Dopamina/metabolismo , Nicotina/farmacologia , Psicotrópicos/farmacologia , Recompensa , Amidoidrolases/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Avaliação Pré-Clínica de Medicamentos , Inibidores Enzimáticos/farmacocinética , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/toxicidade , Masculino , Camundongos , Agonistas Nicotínicos/farmacologia , Distribuição Aleatória , Ratos Sprague-Dawley , Comportamento Espacial/efeitos dos fármacos , Comportamento Espacial/fisiologia
6.
PLoS One ; 13(8): e0201689, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30092007

RESUMO

Mindfulness based stress reduction (MBSR) training has been proposed to improve attentional skills by modulating thalamo-cortical loops that affect the sensitivity of relevant cortical areas like the somatosensory cortex. This modulation may be reflected in the electroencephalographic (EEG) alpha rhythm, and could affect the processing of subsequently applied intracutaneous electrical stimuli. Participants took part in an MBSR training and participated in two EEG sessions. EEG was measured in variants of an endogenous orienting paradigm in which attention had to be directed to the left or right forearm. After the orienting interval, the electrical stimulus was applied, equally likely on the attended or the unattended forearm. One group of participants took part in the EEG session before and after the training, while the other group took part after the training, and another time, eight weeks later. The influence of the MBSR training and spatial attention were examined with behavioral measures, lateralized alpha power within the orienting interval, and with event-related potentials (ERPs) evoked by the electrical stimuli. Self-reported mindfulness was clearly affected by the training, but no influence was found on other behavioral measures. Alpha power was clearly lateralized due to spatial attention and several ERP components (N130, N180, P340) were modulated by spatial attention but no support was found for an influence of the MBSR training. Finally, analyses revealed that individual differences in training time modulated some of the observed effects, but no support was found for an influence on attentional orienting.


Assuntos
Atenção , Estimulação Elétrica , Atenção Plena , Comportamento Espacial/fisiologia , Adulto , Eletroencefalografia , Potenciais Evocados , Humanos , Estresse Psicológico/psicologia , Estresse Psicológico/terapia , Inquéritos e Questionários , Adulto Jovem
7.
Ann Dyslexia ; 68(2): 145-164, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29931552

RESUMO

The aim of this study was to gain additional knowledge about the asynchrony phenomenon in developmental dyslexia, especially when spatial selective attention is manipulated. Adults with developmental dyslexia and non-impaired readers underwent two experimental tasks, one including alphabetic stimuli (pre-lexical consonant-vowel syllables) and the other containing non-alphabetic stimuli (pictures and sounds of animals). Participants were instructed to attend to the right or left hemifields and to respond to all stimuli on that hemifield. Behavioral parameters and event-related potentials were recorded. The main finding was that the dyslexic readers demonstrated asynchrony between the auditory and visual modalities when alphabetic stimuli were presented on the right hemifield. These results suggest that intact reading is linked to a synchronized auditory and visual speed of processing even when spatial selective attention is manipulated. The findings of the current study are discussed in terms of asynchrony between modalities as a neurocognitive marker in developmental dyslexia.


Assuntos
Atenção/fisiologia , Cognição/fisiologia , Dislexia/fisiopatologia , Dislexia/psicologia , Potenciais Evocados/fisiologia , Comportamento Espacial/fisiologia , Estimulação Acústica/métodos , Adulto , Dislexia/diagnóstico , Feminino , Humanos , Masculino , Estimulação Luminosa/métodos , Distribuição Aleatória , Leitura , Adulto Jovem
8.
Behav Brain Res ; 341: 122-128, 2018 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-29288746

RESUMO

In recent years, there has been a marked increase in the use of recreational synthetic psychoactive substances, which is a cause of concern among healthcare providers and legal authorities. In particular, there have been reports on the misuse of 5-(2-aminopropyl)indole (5-API; 5-IT), a new synthetic drug, and of fatal and non-fatal intoxication. Despite these reports, little is known about its psychopharmacological effects and abuse potential. Here, we investigated the abuse potential of 5-IT by evaluating its rewarding and reinforcing effects through conditioned place preference (CPP) (1, 10, and 30 mg/kg, i.p.) in mice and self-administration test (0.1, 0.3, 1, and 3 mg/kg/inf., i.v.) in rats. We also examined whether 5-IT (1, 3, and 10 mg/kg, i.p.) induces locomotor sensitization in mice following a 7-day treatment and drug challenge. Then, we explored the effects of 5-IT (10 mg/kg, i.p.) on dopamine-related genes in the striatum, prefrontal cortex (PFC), and substantia nigra pars compacta (SNc)/ventral tegmental (VTA) of mice by quantitative real-time polymerase chain reaction. 5-IT produced CPP in mice but was not reliably self-administered by rats. 5-IT also induced locomotor sensitization following repeated administration and drug challenge. Moreover, 5-IT increased mRNA levels of dopamine D1 receptor in the striatum and PFC and dopamine transporter in the SNc/VTA of mice. These results indicate that 5-IT has psychostimulant and rewarding properties, which may be attributed to its ability to affect the dopaminergic system in the brain. These findings suggest that 5-IT poses a substantial risk for abuse and addiction in humans.


Assuntos
Dopaminérgicos/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Indóis/farmacologia , Psicotrópicos/farmacologia , Receptores de Dopamina D1/metabolismo , Recompensa , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Comportamento Espacial/efeitos dos fármacos , Comportamento Espacial/fisiologia
9.
Glia ; 65(12): 1944-1960, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28885722

RESUMO

Astrocytes interact with neurons at the cellular level through modulation of synaptic formation, maturation, and function, but the impact of such interaction into behavior remains unclear. Here, we studied the dominant negative SNARE (dnSNARE) mouse model to dissect the role of astrocyte-derived signaling in corticolimbic circuits, with implications for cognitive processing. We found that the blockade of gliotransmitter release in astrocytes triggers a critical desynchronization of neural theta oscillations between dorsal hippocampus and prefrontal cortex. Moreover, we found a strong cognitive impairment in tasks depending on this network. Importantly, the supplementation with d-serine completely restores hippocampal-prefrontal theta synchronization and rescues the spatial memory and long-term memory of dnSNARE mice. We provide here novel evidence of long distance network modulation by astrocytes, with direct implications to cognitive function.


Assuntos
Astrócitos/metabolismo , Cognição/fisiologia , Hipocampo/citologia , Córtex Pré-Frontal/fisiologia , Transdução de Sinais/fisiologia , Animais , Astrócitos/patologia , Astrócitos/ultraestrutura , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/genética , Doxiciclina/farmacologia , Proteína Glial Fibrilar Ácida/metabolismo , Ácido Glutâmico/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Transgênicos , Modelos Neurológicos , Neurônios/ultraestrutura , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/efeitos dos fármacos , Reconhecimento Psicológico/fisiologia , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Proteínas SNARE/genética , Proteínas SNARE/metabolismo , Serina/farmacologia , Comportamento Espacial/fisiologia , Ritmo Teta/efeitos dos fármacos , Ritmo Teta/genética
10.
Behav Brain Res ; 332: 1-6, 2017 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-28559179

RESUMO

Mitragynine is the main psychoactive ingredient of the herbal drug preparation Kratom (Ketum), derived from the plant Mitragyna speciosa. Kratom is a widely abused drug in Southeast Asian and has a psychostimulant profile at low-medium doses, while high doses have opioidergic effects. Mitragynine was shown to possess opiate receptor affinity. However, its role in the behavioural effects of mitragynine is unclear. Here we asked whether the reinforcing effects of mitragynine are mediated by opiate receptors using a conditioned place preference (CPP) paradigm in rats. In the first experiment we tested the effects of the opiate receptor antagonist naloxone (0.1, 0.3 and 1.0mg/kg) on the acquisition of mitragynine (10mg/kg)-induced CPP. In the second experiment, we tested the involvement of opiate receptors in the expression of mitragynine-induced CPP in rats. We found that naloxone suppresses the acquisition of mitragynine-induced CPP. This effect was already evident at a dose of naloxone (0.1mg/kg) which, by itself, had no conditioned place aversion (CPA) effect. Higher doses of naloxone induced a CPA and blocked mitragynine-induced CPP. In contrast, naloxone had no effect on the expression of mitragynine-induced CPP. These findings suggest that the acquisition, but not the expression of the reinforcing effects of mitragynine is mediated by opiate receptors.


Assuntos
Condicionamento Psicológico/efeitos dos fármacos , Psicotrópicos/farmacologia , Receptores Opioides/metabolismo , Alcaloides de Triptamina e Secologanina/farmacologia , Comportamento Espacial/efeitos dos fármacos , Animais , Condicionamento Psicológico/fisiologia , Relação Dose-Resposta a Droga , Masculino , Mitragyna , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Naloxona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Folhas de Planta , Psicotrópicos/isolamento & purificação , Ratos Sprague-Dawley , Reforço Psicológico , Alcaloides de Triptamina e Secologanina/isolamento & purificação , Comportamento Espacial/fisiologia , Transtornos Relacionados ao Uso de Substâncias/tratamento farmacológico , Transtornos Relacionados ao Uso de Substâncias/metabolismo
11.
Cereb Cortex ; 27(2): 1457-1471, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-26759482

RESUMO

Spatial knowledge about an environment can be cued from memory by perception of a visual scene during active navigation or by imagination of the relationships between nonvisible landmarks, such as when providing directions. It is not known whether these different ways of accessing spatial knowledge elicit the same representations in the brain. To address this issue, we scanned participants with fMRI, while they performed a judgment of relative direction (JRD) task that required them to retrieve real-world spatial relationships in response to either pictorial or verbal cues. Multivoxel pattern analyses revealed several brain regions that exhibited representations that were independent of the cues to access spatial memory. Specifically, entorhinal cortex in the medial temporal lobe and the retrosplenial complex (RSC) in the medial parietal lobe coded for the heading assumed on a particular trial, whereas the parahippocampal place area (PPA) contained information about the starting location of the JRD. These results demonstrate the existence of spatial representations in RSC, ERC, and PPA that are common to visually guided navigation and spatial imagery.


Assuntos
Mapeamento Encefálico , Encéfalo/fisiologia , Memória/fisiologia , Percepção Espacial/fisiologia , Comportamento Espacial/fisiologia , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Imagens, Psicoterapia/métodos , Imageamento por Ressonância Magnética/métodos , Masculino , Adulto Jovem
12.
Eur J Pharmacol ; 795: 13-21, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27915041

RESUMO

Neuroinflammation is known as a risk factor for cognitive deficit and dementia and its incidence increases with aging. S-allyl cysteine (SAC) is the active and main component of aged garlic extract with anti-inflammatory, neuroprotective, and nootropic potential. In this study, the protective effect of SAC against lipopolysaccharide (LPS)-induced cognitive deficit in the rat was investigated. For induction of learning and memory impairment and neuroinflammation, LPS was intraperitoneally injected at a dose of 167µg/kg for 7 days and SAC was administered p.o. at doses of 25, 50, or 100mg/kg/day, 30min after LPS, for seven days. Treatment of LPS-injected rats with SAC at a dose of 100mg/kg improved spatial recognition memory in Y maze, discrimination ratio in novel object discrimination task, and retention and recall in passive avoidance test. In addition, SAC at the latter dose mitigated lipid peroxidation marker malondialdehyde (MDA) and augmented key antioxidant defensive elements including superoxide dismutase (SOD), catalase and glutathione (GSH) in hippocampal homogenate and lowered acetylcholinesterase activity. Meanwhile, SAC down-regulated hippocampal nuclear factor-B, toll-like receptor 4 (TLR4), glial fibrillary acidic protein (GFAP), and interleukin 1ß (IL-1ß) and up-regulated nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in addition to lowering iba1-immunoreactive intensity in the hippocampus of LPS-injected group. Taken together, SAC administration could mitigate LPS-induced cognitive deficits via attenuation of oxidative stress, neuroinflammation, astrogliosis, and acetylcholinesterase activity.


Assuntos
Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/prevenção & controle , Cisteína/análogos & derivados , Alho/química , Lipopolissacarídeos/farmacologia , Acetilcolinesterase/metabolismo , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Biomarcadores/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/fisiopatologia , Cisteína/farmacologia , Cisteína/uso terapêutico , Discriminação Psicológica/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Interleucina-1beta/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Proteínas dos Microfilamentos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Comportamento Espacial/efeitos dos fármacos , Comportamento Espacial/fisiologia , Receptor 4 Toll-Like/metabolismo
13.
Proc Natl Acad Sci U S A ; 113(14): 3873-8, 2016 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-27001861

RESUMO

Attention plays a fundamental role in selectively processing stimuli in our environment despite distraction. Spatial attention induces increasing and decreasing power of neural alpha oscillations (8-12 Hz) in brain regions ipsilateral and contralateral to the locus of attention, respectively. This study tested whether the hemispheric lateralization of alpha power codes not just the spatial location but also the temporal structure of the stimulus. Participants attended to spoken digits presented to one ear and ignored tightly synchronized distracting digits presented to the other ear. In the magnetoencephalogram, spatial attention induced lateralization of alpha power in parietal, but notably also in auditory cortical regions. This alpha power lateralization was not maintained steadily but fluctuated in synchrony with the speech rate and lagged the time course of low-frequency (1-5 Hz) sensory synchronization. Higher amplitude of alpha power modulation at the speech rate was predictive of a listener's enhanced performance of stream-specific speech comprehension. Our findings demonstrate that alpha power lateralization is modulated in tune with the sensory input and acts as a spatiotemporal filter controlling the read-out of sensory content.


Assuntos
Atenção/fisiologia , Percepção Auditiva/fisiologia , Ondas Encefálicas/fisiologia , Audição/fisiologia , Análise Espaço-Temporal , Percepção da Fala/fisiologia , Fala/fisiologia , Estimulação Acústica , Adulto , Córtex Auditivo/fisiologia , Mapeamento Encefálico , Feminino , Lateralidade Funcional/fisiologia , Humanos , Magnetoencefalografia , Masculino , Tempo de Reação , Comportamento Espacial/fisiologia , Adulto Jovem
14.
Neuropsychopharmacology ; 41(3): 811-21, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26171719

RESUMO

Overconsumption of dietary fat is increasingly linked with motivational and emotional impairments. Human and animal studies demonstrate associations between obesity and blunted reward function at the behavioral and neural level, but it is unclear to what degree such changes are a consequence of an obese state and whether they are contingent on dietary lipid class. We sought to determine the impact of prolonged ad libitum intake of diets rich in saturated or monounsaturated fat, separate from metabolic signals associated with increased adiposity, on dopamine (DA)-dependent behaviors and to identify pertinent signaling changes in the nucleus accumbens (NAc). Male rats fed a saturated (palm oil), but not an isocaloric monounsaturated (olive oil), high-fat diet exhibited decreased sensitivity to the rewarding (place preference) and locomotor-sensitizing effects of amphetamine as compared with low-fat diet controls. Blunted amphetamine action by saturated high-fat feeding was entirely independent of caloric intake, weight gain, and plasma levels of leptin, insulin, and glucose and was accompanied by biochemical and behavioral evidence of reduced D1R signaling in the NAc. Saturated high-fat feeding was also tied to protein markers of increased AMPA receptor-mediated plasticity and decreased DA transporter expression in the NAc but not to alterations in DA turnover and biosynthesis. Collectively, the results suggest that intake of saturated lipids can suppress DA signaling apart from increases in body weight and adiposity-related signals known to affect mesolimbic DA function, in part by diminishing D1 receptor signaling, and that equivalent intake of monounsaturated dietary fat protects against such changes.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Dopamina/metabolismo , Núcleo Accumbens/metabolismo , Azeite de Oliva/administração & dosagem , Óleos de Plantas/administração & dosagem , Receptores de Dopamina D1/metabolismo , Anfetamina/farmacologia , Animais , Benzazepinas/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Dieta Hiperlipídica/métodos , Agonistas de Dopamina/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Núcleo Accumbens/efeitos dos fármacos , Óleo de Palmeira , Distribuição Aleatória , Ratos Wistar , Receptores de AMPA/metabolismo , Receptores de Dopamina D1/agonistas , Recompensa , Transdução de Sinais , Comportamento Espacial/efeitos dos fármacos , Comportamento Espacial/fisiologia
15.
ACS Chem Neurosci ; 6(11): 1813-24, 2015 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-26325040

RESUMO

3-Iodobenzoyl naltrexamine (IBNtxA) is a potent analgesic belonging to the pharmacologically diverse 6ß-amidoepoxymorphinan group of opioids. We present the synthesis and pharmacological evaluation of five analogs of IBNtxA. The scaffold of IBNtxA was modified by removing the 14-hydroxy group, incorporating a 7,8 double bond and various N-17 alkyl substituents. The structural modifications resulted in analogs with picomolar affinities for opioid receptors. The lead compound (MP1104) was found to exhibit approximately 15-fold greater antinociceptive potency (ED50 = 0.33 mg/kg) compared with morphine, mediated through the activation of kappa- and delta-opioid receptors. Despite its kappa agonism, this lead derivative did not cause place aversion or preference in mice in a place-conditioning assay, even at doses 3 times the analgesic ED50. However, pretreatment with the lead compound prevented the reward behavior associated with cocaine in a conditioned place preference assay. Together, these results suggest the promise of dual acting kappa- and delta-opioid receptor agonists as analgesics and treatments for cocaine addiction.


Assuntos
Analgésicos Opioides/síntese química , Analgésicos Opioides/farmacologia , Cocaína/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Morfinanos/síntese química , Morfinanos/farmacologia , Analgésicos Opioides/química , Animais , Transtornos Relacionados ao Uso de Cocaína/tratamento farmacológico , Transtornos Relacionados ao Uso de Cocaína/metabolismo , Condicionamento Psicológico/efeitos dos fármacos , Condicionamento Psicológico/fisiologia , Avaliação Pré-Clínica de Medicamentos , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Estrutura Molecular , Morfinanos/química , Naltrexona/análogos & derivados , Naltrexona/química , Nociceptividade/efeitos dos fármacos , Nociceptividade/fisiologia , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/farmacologia , Distribuição Aleatória , Receptores Opioides delta/agonistas , Receptores Opioides delta/metabolismo , Receptores Opioides kappa/agonistas , Receptores Opioides kappa/genética , Receptores Opioides kappa/metabolismo , Receptores Opioides mu/genética , Receptores Opioides mu/metabolismo , Recompensa , Comportamento Espacial/efeitos dos fármacos , Comportamento Espacial/fisiologia
16.
J Vestib Res ; 25(2): 47-55, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26410669

RESUMO

This study investigated whether spatial aspects of an information processing task influence dual-task interference. Two groups (Older/Young) of healthy adults participated in dual-task experiments. Two auditory information processing tasks included a frequency discrimination choice reaction time task (non-spatial task) and a lateralization choice reaction time task (spatial task). Postural tasks included combinations of standing with eyes open or eyes closed on either a fixed floor or a sway-referenced floor. Reaction times and postural sway via center of pressure were recorded. Baseline measures of reaction time and sway were subtracted from the corresponding dual-task results to calculate reaction time task costs and postural task costs. Reaction time task cost increased with eye closure (p = 0.01), sway-referenced flooring (p < 0.0001), and the spatial task (p = 0.04). Additionally, a significant (p = 0.05) task x vision x age interaction indicated that older subjects had a significant vision X task interaction whereas young subjects did not. However, when analyzed by age group, the young group showed minimal differences in interference for the spatial and non-spatial tasks with eyes open, but showed increased interference on the spatial relative to non-spatial task with eyes closed. On the contrary, older subjects demonstrated increased interference on the spatial relative to the non-spatial task with eyes open, but not with eyes closed. These findings suggest that visual-spatial interference may occur in older subjects when vision is used to maintain posture.


Assuntos
Envelhecimento/fisiologia , Atenção/fisiologia , Percepção Auditiva/fisiologia , Retroalimentação Sensorial/fisiologia , Mascaramento Perceptivo/fisiologia , Equilíbrio Postural/fisiologia , Tempo de Reação , Comportamento Espacial/fisiologia , Estimulação Acústica , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Discriminação Psicológica/fisiologia , Feminino , Humanos , Masculino , Desempenho Psicomotor/fisiologia , Distribuição Aleatória , Localização de Som/fisiologia , Percepção Espacial/fisiologia , Percepção Visual/fisiologia , Adulto Jovem
17.
Neuron ; 87(4): 882-92, 2015 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-26291168

RESUMO

The frontal lobes control wide-ranging cognitive functions; however, functional subdivisions of human frontal cortex are only coarsely mapped. Here, functional magnetic resonance imaging reveals two distinct visual-biased attention regions in lateral frontal cortex, superior precentral sulcus (sPCS) and inferior precentral sulcus (iPCS), anatomically interdigitated with two auditory-biased attention regions, transverse gyrus intersecting precentral sulcus (tgPCS) and caudal inferior frontal sulcus (cIFS). Intrinsic functional connectivity analysis demonstrates that sPCS and iPCS fall within a broad visual-attention network, while tgPCS and cIFS fall within a broad auditory-attention network. Interestingly, we observe that spatial and temporal short-term memory (STM), respectively, recruit visual and auditory attention networks in the frontal lobe, independent of sensory modality. These findings not only demonstrate that both sensory modality and information domain influence frontal lobe functional organization, they also demonstrate that spatial processing co-localizes with visual processing and that temporal processing co-localizes with auditory processing in lateral frontal cortex.


Assuntos
Atenção/fisiologia , Lobo Frontal/fisiologia , Memória de Curto Prazo/fisiologia , Rede Nervosa/fisiologia , Comportamento Espacial/fisiologia , Estimulação Acústica/métodos , Adulto , Mapeamento Encefálico/métodos , Feminino , Humanos , Masculino , Estimulação Luminosa/métodos , Fatores de Tempo , Adulto Jovem
18.
J Stroke Cerebrovasc Dis ; 24(8): 1905-16, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26051668

RESUMO

BACKGROUND: Clinical research, together with computed tomography/magnetic resonance imaging findings, proves that ischemic stroke (IS) that damages auditory pathways can cause hearing loss and impairment of higher auditory processes such as sound localization. The goal of the study was to find possible correlations between the IS risk factors, ischemic lesion volume and localization, neurologic status, and the sound localization capability in acute IS patients. METHODS: We consecutively enrolled 61 IS patients into the study. The control group consisted of 60 healthy volunteers. All neuro-otological evaluations were performed up to 30 days from the incidence of stroke. All the subjects underwent the horizontal minimum audible angle test (HMAAT) and standard tonal and speech audiometric assessments. RESULTS: HMMAT results were significantly worse in the IS patients and were present in 82.0% of the patients. There were more patients with unilateral disturbances than with bilateral ones (54.1% versus 27.9%). It was the characteristics of the ischemic lesions that correlated strongly with the sound localization deterioration, that is, their bilateral (the 90° azimuth, P = .018; the 180°, P = .002), multiple (the 45°, P = .020; the 180°, P = .007; the 225°, P = .047), and lacunar character (the 90°, P = .015; the 225°, P = .042). Differences in the types of HMAAT results were significant for lesions in the frontal and the temporal lobe (P = .018 and P = .040). In addition, worse sound localization ability was more common in patients with poor speech discrimination and the bilateral sensorineural hearing loss. We have not found statistically significant correlations for other analyzed factors such as the cortical/subcortical character of the lesions, the patients' neurologic status, and cerebrovascular risk factors. CONCLUSIONS: Sound localization impairment is common in IS patients and it is the multiple, bilateral, and lacunar character of the ischemic lesions that seems to be strongly positively correlated with the disturbance of the sound localization ability.


Assuntos
Transtornos da Percepção Auditiva/etiologia , Isquemia Encefálica/complicações , Comportamento Espacial/fisiologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/etiologia , Estimulação Acústica , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Audiometria , Estudos de Casos e Controles , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Localização de Som , Tomógrafos Computadorizados , Adulto Jovem
19.
Biosystems ; 130: 28-36, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25766395

RESUMO

Leeches are fascinating creatures: they have simple modular nervous circuitry yet exhibit a rich spectrum of behavioural modes. Leeches could be ideal blue-prints for designing flexible soft robots which are modular, multi-functional, fault-tolerant, easy to control, capable for navigating using optical, mechanical and chemical sensorial inputs, have autonomous inter-segmental coordination and adaptive decision-making. With future designs of leech-robots in mind we study how leeches behave in geometrically constrained spaces. Core results of the paper deal with leeches exploring a row of rooms arranged along a narrow corridor. In laboratory experiments we find that rooms closer to ends of the corridor are explored by leeches more often than rooms in the middle of the corridor. Also, in series of scoping experiments, we evaluate leeches capabilities to navigating in mazes towards sources of vibration and chemo-attraction. We believe our results lay foundation for future developments of robots mimicking behaviour of leeches.


Assuntos
Comportamento Exploratório/fisiologia , Sanguessugas/fisiologia , Atividade Motora/fisiologia , Comportamento Espacial/fisiologia , Animais
20.
J Neurosci ; 34(27): 9067-75, 2014 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-24990927

RESUMO

Although commonly viewed as a sensory information relay center, the thalamus has been increasingly recognized as an essential node in various higher-order cognitive circuits, and the underlying thalamocortical interaction mechanism has attracted increasing scientific interest. However, the development of thalamocortical connections and how such development relates to cognitive processes during the earliest stages of life remain largely unknown. Leveraging a large human pediatric sample (N = 143) with longitudinal resting-state fMRI scans and cognitive data collected during the first 2 years of life, we aimed to characterize the age-dependent development of thalamocortical connectivity patterns by examining the functional relationship between the thalamus and nine cortical functional networks and determine the correlation between thalamocortical connectivity and cognitive performance at ages 1 and 2 years. Our results revealed that the thalamus-sensorimotor and thalamus-salience connectivity networks were already present in neonates, whereas the thalamus-medial visual and thalamus-default mode network connectivity emerged later, at 1 year of age. More importantly, brain-behavior analyses based on the Mullen Early Learning Composite Score and visual-spatial working memory performance measured at 1 and 2 years of age highlighted significant correlations with the thalamus-salience network connectivity. These results provide new insights into the understudied early functional brain development process and shed light on the behavioral importance of the emerging thalamocortical connectivity during infancy.


Assuntos
Mapeamento Encefálico , Córtex Cerebral/crescimento & desenvolvimento , Desenvolvimento Infantil , Cognição/fisiologia , Rede Nervosa/crescimento & desenvolvimento , Tálamo/crescimento & desenvolvimento , Córtex Cerebral/fisiologia , Feminino , Seguimentos , Jogos Experimentais , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Memória de Curto Prazo/fisiologia , Rede Nervosa/fisiologia , Vias Neurais/crescimento & desenvolvimento , Vias Neurais/fisiologia , Testes Neuropsicológicos , Comportamento Espacial/fisiologia , Tálamo/fisiologia
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