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1.
J Atten Disord ; 28(3): 335-349, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38084076

RESUMO

OBJECTIVE: Interindividual similarity refers to how similarly individuals respond when receiving the same stimulus or intervention. In this study, we aimed to examine interindividual similarity in adults with ADHD. METHOD: We used the cosine similarity index of ex-Gaussian reaction time (RT) vectors of mu, sigma, and tau parameters during a Stroop task. RESULTS: Our results demonstrate that the ADHD group exhibits a reduced interindividual similarity index in their ex-Gaussian RT vectors for congruent stimuli compared to the healthy control group. Importantly, we did not find significant differences in the interindividual similarity index to incongruent stimuli between both groups, thus suggesting that this reduced index was selective for congruent stimuli. CONCLUSION: Our findings highlight that ADHD adults exhibit more significant interindividual differences in cognitive functioning when processing congruent stimuli than healthy controls. These results provide new insights into the selective mechanisms underlying ADHD and may contribute to developing new targeted interventions for this disorder.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Adulto , Humanos , Tempo de Reação , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Distribuição Normal , Cognição , Teste de Stroop
2.
Synapse ; 77(1): e22252, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36099479

RESUMO

Previous studies demonstrated that in vitro preparations of the isolated vestibular system of diverse animal species still exhibit stable resting electrical activity and mechanically evoked synaptic transmission between hair cells and primary afferent endings. However, there are no reports related to their neurodevelopment. Therefore, this research aimed to examine whether NMDA receptors mediate these electrical signals in an isolated preparation of the chicken vestibular system at three developmental stages, E15, E18, and E21. We found that the spontaneous and mechanically evoked discharges from primary afferents of the posterior semicircular canal were modulated by agonists NMDA and glycine, but not by the agonist d-serine applied near the synapses. Moreover, the individually applied by bath perfusion of three NMDA receptor antagonists (MK-801, ifenprodil, and 2-naphthoic acid) or high Mg2+ decreased the resting discharge rate, the NMDA response, and the discharge rate of mechanically evoked activity from these primary afferents. Furthermore, we found that the vestibular ganglion shows a stage-dependent increase in the expression of NMDA receptor subunits GluN1, GluN2 (A-C), and GluN3 (A-B), being greater at E21, except for GluN2D, which was inversely related to the developmental stage. However, in the crista ampullaris, the expression pattern remained constant throughout development. This could suggest the possible existence of presynaptic NMDA receptors. Our results highlight that although the NMDA receptors are functionally active at the early embryonic stages of the vestibular system, NMDA and glycine reach their mature functionality to increase NMDA responses close to hatching (E21).


Assuntos
Galinhas , Receptores de N-Metil-D-Aspartato , Animais , Receptores de N-Metil-D-Aspartato/metabolismo , Galinhas/metabolismo , N-Metilaspartato , Sistema Vestibular , Glicina
4.
Expert Opin Ther Pat ; 31(1): 81-90, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32945223

RESUMO

INTRODUCTION: OX40 is an immune checkpoint in cancer and its presence in cancer is a good prognosis, making it a highly relevant target for the development of new immunotherapies. AREAS COVERED: The patent literature reveals vital information on new trends in cancer therapies. The authors used the patent databases of the six major patent offices in the world: United States Patent and Trademark Office, European Patent Office, World Intellectual Property Organization, Japan Patent Office, State Office of Intellectual Property of China and Korean Intellectual Property Office, to generate a panorama of patents related to OX40 agonists. Specific patents have been grouped into innovative patents and adoption patents. EXPERT OPINION: An increasing trend in the development of OX40 agonists in cancer, particularly in the years 2018 and 2019. United States was the leader in generating patents, followed by China and England. Major pharmaceutical companies have at least one anti-OX40 agonist, MEDI6469 and MEDI-0562 (AstraZeneca), PF-04518600 (Pfizer), GSK3174998 (GlaxoSmithKline), BMS-986,178 (Bristol-Myers Squibb) and MOXR0916 (Roche), which represent 68% of clinical trials conducted with OX40 agonists.


Assuntos
Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Receptores OX40/agonistas , Animais , Desenvolvimento de Medicamentos , Humanos , Imunoterapia , Neoplasias/imunologia , Neoplasias/patologia , Patentes como Assunto , Receptores OX40/imunologia
5.
Front Neurosci ; 14: 490, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32528244

RESUMO

In previous reports, we developed a method to apply Brownian optogenetic noise-photostimulation (BONP, 470 nm) up to 0.67 mW on the barrel cortex of in vivo ChR2 transgenic mice. In such studies, we found that the BONP produces an increase in the evoked field potentials and the neuronal responses of pyramidal neurons induced by somatosensory mechanical stimulation. Here we extended such findings by examining whether the same type of BONP augments the Na+ current amplitude elicited by voltage-clamp ramps of dissociated pyramidal neurons from the somatosensory cortex of ChR2 transgenic and wild type mice. We found that in all neurons from the ChR2 transgenic mice, but none of the wild type mice, the peak amplitude of a TTX-sensitive Na+ current and its inverse of latency exhibited inverted U-like graphs as a function of the BONP level. It means that an intermediate level of BONP increases both the peak amplitude of the Na+ current and its inverse of latency. Our research suggests that the impact of BONP on the Na+ channels of pyramidal neurons could be associated with the observed augmentation-effects in our previous in vivo preparation. Moreover, it provides caution information for the use of an appropriate range of light intensity, <0.67 mW, which could avoid opto non-genetics (also termed "optonongenetic") related responses due to light-induced temperature changes.

6.
Expert Opin Ther Pat ; 30(7): 487-494, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32397849

RESUMO

INTRODUCTION: Due to the primary role of PD-1 and LAG-3 in regulating the immune response in tumors, there is a need to develop therapies focused on the inhibition of PD-1 and LAG-3 in order to improve the immune response in patients with cancer. The authors of US2018326054 patent propose a method to eradicate cancer by using bispecific anti-PD-1/LAG-3 antibodies. AREAS COVERED: The US2018326054 patent describes anti-PD-1/LAG3 antibodies, pharmaceutical composition that contains it, and their application for cancer treatment, particularly pancreatic carcinoma. Proof concept and preclinical results show anti-PD-1/LAG-3 bispecific antibodies bind and are internalized by CD4 + T cells thereby increasing their effector functions (release of Granzyme B and INF-γ) in the presence of tumor cells, and completely suppress tumors in a murine model. EXPERT OPINION: Anti-PD-1/LAG-3 bispecific antibodies of the US2018326054 patent are new in a general concept, but treatment data is only shown for pancreatic carcinoma. The results to be obtained in future clinical trials of safety and efficacy could conclude whether these bispecific anti-PD-1/LAG-3 antibodies will be useful in a cancer treatment scheme.


Assuntos
Anticorpos Biespecíficos/administração & dosagem , Antígenos CD/imunologia , Neoplasias/terapia , Receptor de Morte Celular Programada 1/imunologia , Animais , Anticorpos Biespecíficos/imunologia , Humanos , Imunoterapia/métodos , Camundongos , Neoplasias/imunologia , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/terapia , Patentes como Assunto , Proteína do Gene 3 de Ativação de Linfócitos
7.
Front Neurosci ; 14: 38, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32076397

RESUMO

The hemodynamic response is a neurovascular and metabolic process in which there is rapid delivery of blood flow to a neuronal tissue in response to neuronal activation. The functional magnetic resonance imaging (fMRI) and the functional near-infrared spectroscopy (fNIRS), for instance, are based on the physiological principles of such hemodynamic responses. Both techniques allow the mapping of active neuronal regions in which the neurovascular and metabolic events are occurring. However, although both techniques have revolutionized the neurosciences, they are mostly employed for neuroimaging of the human brain but not for the spinal cord during functional tasks. Moreover, little is known about other techniques measuring the hemodynamic response in the spinal cord. The purpose of the present study was to show for the first time that a simple optical system termed direct current photoplethysmography (DC-PPG) can be employed to detect hemodynamic responses of the spinal cord and the brainstem during the functional activation of the spinal central pattern generator (CPG). In particular, we positioned two DC-PPG systems directly on the brainstem and spinal cord during fictive scratching in the cat. The optical DC-PPG systems allowed the trial-by-trial recording of massive hemodynamic signals. We found that the "strength" of the flexor-plus-extensor motoneuron activities during motor episodes of fictive scratching was significantly correlated to the "strengths" of the brainstem and spinal DC-PPG signals. Because the DC-PPG was robustly detected in real-time, we claim that such a functional signal reflects the hemodynamic mass action of the brainstem and spinal cord associated with the CPG motor action. Our findings shed light on an unexplored hemodynamic observable of the spinal CPGs, providing a proof of concept that the DC-PPG can be used for the assessment of the integrity of the human CPGs.

8.
Expert Opin Ther Pat ; 30(3): 159-162, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31944149

RESUMO

Introduction: KIR is an inhibitory receptor expressed by natural killer cells that suppress the immune response against tumor cells. There is a great need to discover and develop new therapies focused on inhibiting the action of KIR and consequently improving the immune response in the various types of cancer. Authors of US9879082 and US2018208652 patents propose a method to eradicate cancer that utilizes anti-KIR antibody.Areas covered: US9879082 and US2018208652 patents describe an anti-KIR antibody, a pharmaceutical composition that contains it, and their application for cancer treatment, particularly, multiple myeloma and acute myeloid leukemia. Anti-KIR antibody is used to a dosage of 0.0003-3 mg antibody/kg patient weight, and is suspended in an isotonic solution consisting of sodium phosphate, sucrose, NaCl, and polysorbate 80.Expert opinion: The results of the clinical trials only support trials regarding the pharmacokinetic, pharmacodynamic, safety, and tolerability. In addition, these results demonstrate that treatment with the anti-KIR antibody can induce an antitumor response in cancer patients.


Assuntos
Anticorpos/administração & dosagem , Imunoterapia/métodos , Receptores KIR/antagonistas & inibidores , Animais , Anticorpos/imunologia , Humanos , Células Matadoras Naturais/efeitos dos fármacos , Células Matadoras Naturais/imunologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/imunologia , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/imunologia , Patentes como Assunto , Receptores KIR/imunologia
9.
Oncology ; 97(6): 373-382, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31430760

RESUMO

INTRODUCTION: Breast cancer is one of the leading causes of death worldwide and is the result of dysregulation of various signaling pathways in mammary epithelial cells. The mortality rate in patients suffering from breast cancer is high because the tumor cells have a prominent invasive capacity towards the surrounding tissues. Previous studies carried out in tumor cell models show that voltage-gated ion channels may be important molecular actors that contribute to the migratory and invasive capacity of the tumor cells. METHODS: In this study, by using an experimental strategy that combines cell and molecular biology assays with electrophysiological recording, we sought to determine whether the voltage-dependent sodium channel NaV1.5 regulates the migratory capacity of the human breast cancer cell line MDA-MB 231, when cells are maintained in the presence of epidermal growth factor (EGF), as an inductor of the epithelial-mesenchymal transition. RESULTS: Our data show that EGF stimulates the migratory capacity of MDA-MB 231 cells, by regulating the functional expression of NaV1.5 channels. Consistent with this, the stimulatory actions of the growth factor were prevented by the use of tetrodotoxin, an Na+ channel selective blocker, as well as by resveratrol, an antioxidant that can also affect Na+ channel activity. DISCUSSION: The understanding of molecular mechanisms, such as the EGF pathway in the progression of breast cancer is fundamental for the design of more effective therapeutic strategies for the disease.


Assuntos
Neoplasias da Mama/patologia , Fator de Crescimento Epidérmico/farmacologia , Canal de Sódio Disparado por Voltagem NAV1.5/fisiologia , Cálcio/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal , Feminino , Humanos , Canal de Sódio Disparado por Voltagem NAV1.5/análise , Resveratrol/farmacologia
10.
eNeuro ; 6(2)2019.
Artigo em Inglês | MEDLINE | ID: mdl-31043462

RESUMO

There is evidence that a variety of central and afferent stimuli, including swallowing, can produce phase resetting in the respiratory rhythmicity. Also, there are reports about the intrinsic linkage between locomotion and respiration. However, little is known about the interaction between the central pattern generators (CPGs) for scratching and respiration. The present study aims to examine whether the activation of scratching CPG produces phase resetting of the respiratory rhythm. We employed decerebrate cats to apply brief tactile stimuli to the pinna during the inspiratory-expiratory transition. We observed that those stimuli to the pinna not eliciting fictive scratching did not reset the respiratory rhythm. However, when the pinna stimuli elicited fictive scratching, then the respiratory rhythm exhibited a significant phase resetting. We also found interneurons in the medulla oblongata exhibiting phase resetting related to scratching-CPG episodes. This second finding suggests that this type of resetting involves brainstem components of the respiratory CPG. These results shed new light on the resetting action from a spinal CPG on the respiratory rhythm.


Assuntos
Geradores de Padrão Central/fisiologia , Interneurônios/fisiologia , Bulbo/fisiologia , Periodicidade , Reflexo/fisiologia , Taxa Respiratória/fisiologia , Medula Espinal/fisiologia , Percepção do Tato/fisiologia , Animais , Gatos , Estado de Descerebração/fisiopatologia , Feminino , Masculino
11.
Front Integr Neurosci ; 13: 75, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32038185

RESUMO

Spinal motoneurons exhibit sustained afterdischarges and plateau potentials following a brief high-frequency stimulation of Ia afferents. Also, there is evidence that spinal cord interneurons exhibit plateau potentials. However, to our knowledge, there are no reports about the possible afterdischarge behavior of lumbar spinal interneurons activated by Ia afferents. Given that there are spinal interneurons receiving monosynaptic inputs from Ia afferents, these cells could then be activated in parallel to motoneurons after repetitive muscle stretch. We explored this possibility in cats with a precollicular-postmammillary decerebration. We found that a brief high-frequency stimulation of Ia afferents produces afterdischarges that are highly correlated to a DC slow potential recorded at the cord dorsum. We conclude that in the cat spinal cord, not only the motoneurons but also the interneurons from the superficial and deep dorsal horn produce sustained afterdischarges, thus highlighting the importance of interneurons in the spinal neuronal circuitry. The significance of our finding is that it opens the possibility that the spinal cord interneurons activated by Ia afferents could also exhibit bistability, a relevant phenomenon well-characterized in the motoneurons.

12.
Medicine (Baltimore) ; 97(35): e12008, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30170407

RESUMO

The present investigation documents the electrophysiological occurrence of multisensory internal stochastic resonance (MISR) in the human electroencephalographic (EEG) coherence elicited by auditory and visual noise.We define MISR of EEG coherence as the phenomenon for which an intermediate level of input noise of a sensory modality enhances EEG coherence in response to another noisy sensory modality. Here, EEG coherence is computed by the global weighted coherence (GWC), modulated by quasi-Brownian noise. Specifically, we examined whether a particular level of auditory noise together with constant visual noise (experimental condition 1) and a specified level of visual noise together with constant auditory noise (experimental condition 2), improves EEG's GWC. We compared GWC between ongoing EEG basal activity (BA), zero noise (ZN), optimal noise (ON), and high noise (HN).The data disclosed an intermediate level of input noise that enhances the GWC for the majority of the subjects, thus demonstrating for the first time the occurrence of multisensory internal stochastic resonance (SR) in visuoauditory processing within the central nervous system.


Assuntos
Eletroencefalografia/métodos , Potenciais Evocados Auditivos/fisiologia , Potenciais Evocados Visuais/fisiologia , Modelos Neurológicos , Estimulação Acústica , Adulto , Percepção Auditiva/fisiologia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Ruído , Estimulação Luminosa , Processos Estocásticos , Percepção Visual/fisiologia , Adulto Jovem
13.
J Neurophysiol ; 114(4): 2132-43, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26156387

RESUMO

The present investigation documents the electrophysiological occurrence of multisensory stochastic resonance in the human visual pathway elicited by tactile noise. We define multisensory stochastic resonance of brain evoked potentials as the phenomenon in which an intermediate level of input noise of one sensory modality enhances the brain evoked response of another sensory modality. Here we examined this phenomenon in visual evoked potentials (VEPs) modulated by the addition of tactile noise. Specifically, we examined whether a particular level of mechanical Gaussian noise applied to the index finger can improve the amplitude of the VEP. We compared the amplitude of the positive P100 VEP component between zero noise (ZN), optimal noise (ON), and high mechanical noise (HN). The data disclosed an inverted U-like graph for all the subjects, thus demonstrating the occurrence of a multisensory stochastic resonance in the P100 VEP.


Assuntos
Encéfalo/fisiologia , Potenciais Evocados Visuais/fisiologia , Percepção do Tato/fisiologia , Vias Visuais/fisiologia , Percepção Visual/fisiologia , Adulto , Eletroencefalografia , Feminino , Humanos , Masculino , Modelos Neurológicos , Estimulação Física/métodos , Processos Estocásticos , Adulto Jovem
14.
Int J Dev Neurosci ; 44: 92-101, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26070862

RESUMO

We performed intracellular and single-unit extracellular recordings of neurons from different regions of the basilar papilla in the isolated chicken inner ear. We compared the spontaneous activity and the response properties of these neurons in embryos at E15 versus posthatching animals at P1. The recordings were carried out from the apical (position 0) to the basal extension at three positions of the basilar papilla, at 5%, 10% and 40% of the entire length of the cochlea. We found that the neurons at E15 recorded from these three regions exhibited a significant higher coefficient of variation compared with those neurons at P1 recorded in the same positions. This shows that in the posthatching age P1 the neurons from the whole basilar papilla become less irregular. We found that the intracellular action potential waveforms generated at E15 had small amplitudes and small depolarization slopes in comparison to those recorded at P1, respectively (53 ± 1 mV vs. 62 ± 2 mV; 66 ± 12 mV/msec vs. 166 ± 23 mV/msec). Furthermore, we also found that the response patterns to injection of current steps were phasic, tonic, or in the form of a not yet reported "burst" pattern. Our study shows that the low irregular discharge, the immature action potential waveforms, and the differences in the response patterns to current injection, highlights the important differences between neurons at E15 and P1, consistent with the incapacity of auditory neurons at embryonic age E16, to respond at sound levels <100 decibels.


Assuntos
Potenciais de Ação/fisiologia , Vias Aferentes/fisiologia , Neurônios/fisiologia , Órgão Espiral/citologia , Órgão Espiral/crescimento & desenvolvimento , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Biofísica , Embrião de Galinha , Estimulação Elétrica , Eletrofisiologia
15.
PLoS One ; 9(10): e109534, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25329563

RESUMO

We introduce the behavior of the electrical output response of a magnetic field sensor based on microelectromechanical systems (MEMS) technology under different levels of controlled magnetic noise. We explored whether a particular level of magnetic noise applied on the vicinity of the MEMS sensor can improve the detection of subthreshold magnetic fields. We examined the increase in the signal-to-noise ratio (SNR) of such detected magnetic fields as a function of the magnetic noise intensity. The data disclosed an inverted U-like graph between the SNR and the applied magnetic noise. This finding shows that the application of an intermediate level of noise in the environment of a MEMS magnetic field sensor improves its detection capability of subthreshold signals via the stochastic resonance phenomenon.


Assuntos
Campos Magnéticos , Sistemas Microeletromecânicos/instrumentação , Processos Estocásticos , Humanos , Sistemas Microeletromecânicos/métodos , Modelos Neurológicos , Razão Sinal-Ruído
16.
Neurosci Lett ; 553: 24-8, 2013 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-23954824

RESUMO

The purpose of the present study was to investigate the modulation of spontaneous afferent activity by ATP during embryonic development in a preparation isolated chicken inner ear. This work was performed using multiunit and single-unit extracellular recordings from the posterior semicircular canal nerve and the basilar papilla nerve. α,ß-meATP, a P2X receptor agonist, notably increased the discharge frequency of the vestibular afferents between E15 and E18, but not in the basilar papilla. In contrast, the P2Y receptor agonist UTP produced a slight increase in the discharge frequency of basilar papilla afferents, without apparent changes in the vestibular afferent activity. 2-MeSATP, a P2Y agonist, increased the basal discharge of the primary afferents in a dose-age dependent way, but when we applied the antagonist of P2Y receptor, Reactive Blue 2 (10(-4)M), the effect of 2-MeSATP decreased significantly. This was observed both in vestibule and basilar papilla. Using RT-PCR the presence of P2X3, P2Y1, P2Y2 and P2Y6 mRNA was documented in the vestibular system with more important presence during the early stage (E15) than the later stage (E21), however in the basilar papilla we found only the P2Y1, P2Y2 and P2Y6 mRNA with the same temporal course as in the vestibule. These results confirm our pharmacological findings. Together this data suggests a role for P2X receptors-mediated purinergic signaling in vestibular synaptic organization. Temporal changes in P2Y receptors during development might be involved in the establishment of the endolymphatic ion composition needed for normal vestibular and auditory transduction and/or specific cellular differentiation.


Assuntos
Orelha Interna/metabolismo , Receptores Purinérgicos P2X/metabolismo , Receptores Purinérgicos P2Y/metabolismo , Potenciais de Ação , Vias Aferentes/fisiologia , Animais , Embrião de Galinha , Orelha Interna/inervação , Fibras Nervosas/fisiologia , Órgão Espiral/metabolismo , Agonistas do Receptor Purinérgico P2X/farmacologia , Agonistas do Receptor Purinérgico P2Y/farmacologia , Vestíbulo do Labirinto/inervação , Vestíbulo do Labirinto/metabolismo
17.
Synapse ; 67(7): 374-81, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23401185

RESUMO

The aim of this study was to characterize the effect of γ-aminobutyric acid (GABA) in the resting multiunit activity of the vestibular afferents during development using the isolated inner ear of embryonic and postnatal chickens (E15-E21 and P5). GABA (10(-3) to 10(-5) M; n = 133) and muscimol (10(-3) M) elicited an increase in the frequency of the basal discharge of the vestibular afferents. We found that GABA action was dose-dependent and inversely related to animal age. Thus, the largest effect was observed in embryonic ages such as E15 and E17 and decreases in E21 and P5. The GABAA receptor antagonists, bicuculline (10(-5) M; n = 10) and picrotoxin (10(-4) M; n = 10), significantly decreased the excitatory action of GABA and muscimol (10(-3) M). Additionally, CNQX 10(-6) M, MCPG 10(-5) M and 7ClKyn 10(-5) M (n = 5) were co-applied by bath substitution (n = 5). Both the basal discharge and the GABA action significantly decreased in these experimental conditions. The chloride channel blocker 9-AC 0.5 mM produced an important reduction in the effect of GABA 10(-3) (n = 5) and 10(-4) M (n = 5). Thus, our results suggest an excitatory role of GABA in the resting activity of the vestibular afferents that can be explained by changes in the gradient of concentration of Cl(-) during development. We show for the first time that the magnitude of this GABA effect decreases at later stages of embryonic and early postnatal development. Taking into account the results with glutamatergic antagonists, we conclude that GABA has a presynaptic action but is not the neurotransmitter in the vestibular afferent synapses, although it could act as a facilitator of the spontaneous activity and may regulate glutamate release.


Assuntos
Potenciais de Ação/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Neurônios Aferentes/fisiologia , Nervo Vestibular/fisiologia , Ácido gama-Aminobutírico/metabolismo , Animais , Embrião de Galinha , Canais de Cloreto/antagonistas & inibidores , Cloretos/metabolismo , Antagonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas GABAérgicos/farmacologia , Muscimol/farmacologia , Neurônios Aferentes/metabolismo , Nervo Vestibular/citologia , Nervo Vestibular/embriologia
18.
J Neurophysiol ; 108(4): 1176-85, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22673332

RESUMO

Crossed effects from group I afferents on reflex excitability and their mechanisms of action are not yet well understood. The current view is that the influence is weak and takes place indirectly via oligosynaptic pathways. We examined possible contralateral effects from group I afferents on presynaptic inhibition of Ia terminals in humans and cats. In resting and seated human subjects the soleus (SO) H-reflex was conditioned by an electrical stimulus to the ipsilateral common peroneal nerve (CPN) to assess the level of presynaptic inhibition (PSI_control). A brief conditioning vibratory stimulus was applied to the triceps surae tendon at the contralateral side (to activate preferentially Ia muscle afferents). The amplitude of the resulting H-reflex response (PSI_conditioned) was compared to the H-reflex under PSI_control, i.e., without the vibration. The interstimulus interval between the brief vibratory stimulus and the electrical shock to the CPN was -60 to 60 ms. The H-reflex conditioned by both stimuli did not differ from that conditioned exclusively by the ipsilateral CPN stimulation. In anesthetized cats, bilateral monosynaptic reflexes (MSRs) in the left and right L(7) ventral roots were recorded simultaneously. Conditioning stimulation applied to the contralateral group I posterior biceps and semitendinosus (PBSt) afferents at different time intervals (0-120 ms) did not have an effect on the ipsilateral gastrocnemius/soleus (GS) MSR. An additional experimental paradigm in the cat using contralateral tendon vibration, similar to that conducted in humans, was also performed. No significant differences between GS-MSRs conditioned by ipsilateral PBSt stimulus alone and those conditioned by both ipsilateral PBSt stimulus and contralateral tendon vibration were detected. The present results strongly suggest an absence of effects from contralateral group I fibers on the presynaptic mechanism of MSR modulation in relaxed humans and anesthetized cats.


Assuntos
Lateralidade Funcional/fisiologia , Reflexo H/fisiologia , Músculo Esquelético/fisiologia , Inibição Neural/fisiologia , Terminações Pré-Sinápticas/fisiologia , Vibração , Adulto , Animais , Gatos , Feminino , Humanos , Masculino , Especificidade da Espécie
19.
Rev. neurol. (Ed. impr.) ; 52(11): 665-675, 1 jun., 2011. ilus, tab
Artigo em Espanhol | IBECS | ID: ibc-89252

RESUMO

Introducción. El ácido gamma-aminobutírico (GABA) es el principal neurotransmisor de tipo inhibitorio y sus acciones son mediadas por receptores de tipo ionotrópico (GABAA) y metabotrópico (GABAB), ampliamente distribuidos en el tejido nervioso central. Objetivo. Revisar la estructura de los receptores GABA y su implicación en procesos fisiológicos en el sistema nervioso central. Desarrollo. Se aborda el estudio de la estructura y diversidad de los receptores GABA, especialmente durante el neurodesarrollo, y se hace referencia a la naturaleza excitatoria e inhibitoria de la transmisión gabérgica, donde la participación de los cotransportadores NKCC1 y KCC2 tiene un papel clave en dicha dualidad funcional en la transición de un estadio embrionario a uno posnatal. De igual forma, se plasma el interés por los receptores GABA como diana farmacológica de uso clínico, lo que se manifiesta por la presencia de sitios de modulación alostérica poco explorados en dicho complejo-receptor. Conclusiones. El conocimiento fisiológico y farmacológico de la gran diversidad de subunidades que conforman un determinado subtipo de receptor GABA, así como la correcta expresión en tiempo y espacio para garantizar la viabilidad de un organismo, prometen ser la respuesta a trastornos graves y añejos como la epilepsia o la drogadicción, y tan complejos como el neurodesarrollo (AU)


Introduction. Gamma-aminobutyric acid (GABA) is the most important inhibitory-type neurotransmitter and its actions are mediated by ionotropic (GABAA) and metabotropic (GABAB) type receptors, which are widely distributed throughout the tissue of the central nervous system. Aim. To review the structure of GABA receptors and their involvement in physiological processes in the central nervous system. Development. The study addresses the structure and diversity of the GABA receptors, especially during neurodevelopment, and reference is made to the excitatory and inhibitory nature of GABAergic transmission, where the participation of the cotransporters NKCC1 and KCC2 plays a key role in this functional duality in the transition from an embryonic to a postnatal state. Likewise, the interest in GABA receptors as a pharmacological target for clinical use is also discussed. This is manifested by the presence of under-explored allosteric modulation sites in the aforementioned complex-receptor. Conclusions. The physiological and pharmacological knowledge of the great diversity of subunits that make up a particular subtype of GABA receptor, as well as the correct expression in time and space in order to ensure the viability of the organism, promise to be the answer to long-time severe disorders like epilepsy or drug addiction, and such complex ones as neurodevelopment (AU)


Assuntos
Humanos , Sistema Nervoso/crescimento & desenvolvimento , Ácido gama-Aminobutírico/fisiologia , Receptores de GABA/fisiologia , Transtornos Induzidos por Álcool/fisiopatologia , Benzodiazepinas/farmacocinética , Nociceptores/fisiopatologia
20.
Biomed Microdevices ; 13(2): 303-13, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21113665

RESUMO

We describe a simple procedure to characterize a magnetic field sensor based on microelectromechanical systems (MEMS) technology, which exploits the Lorentz force principle. This sensor is designed to detect, in future applications, the spiking activity of neurons or muscle cells. This procedure is based on the well-known capability that a magnetic MEMS device can be used to sense a small magnetic flux density. In this work, an electronic neuron (FitzHugh-Nagumo) is used to generate controlled spike-like magnetic fields. We show that the magnetic flux density generated by the hardware of this neuron can be detected with a new MEMS magnetic field sensor. This microdevice has a compact resonant structure (700 × 600 × 5 µm) integrated by an array of silicon beams and p-type piezoresistive sensing elements, which need an easy fabrication process. The proposed microsensor has a resolution of 80 nT, a sensitivity of 1.2 V.T(-1), a resonant frequency of 13.87 kHz, low power consumption (2.05 mW), quality factor of 93 at atmospheric pressure, and requires a simple signal processing circuit. The importance of our study is twofold. First, because the artificial neuron can generate well-controlled magnetic flux density, we suggest it could be used to analyze the resolution and performance of different magnetic field sensors intended for neurobiological applications. Second, the introduced MEMS magnetic field sensor may be used as a prototype to develop new high-resolution biomedical microdevices to sense magnetic fields from cardiac tissue, nerves, spinal cord, or the brain.


Assuntos
Células Artificiais/citologia , Fenômenos Eletromagnéticos , Magnetismo/instrumentação , Fenômenos Mecânicos , Microtecnologia/instrumentação , Neurônios/citologia , Eletricidade , Desenho de Equipamento
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