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1.
Cell Rep ; 20(2): 308-318, 2017 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-28700934

RESUMO

The control of targeted reaching is thought to be shaped by distinct subtypes of local GABAergic inhibitory neurons in primary forelimb motor cortex (M1). However, little is known about their action potential firing dynamics during reaching. To address this, we recorded the activity of parvalbumin-expressing (PV+) GABAergic neurons identified from a larger population of fast-spiking units and putative excitatory regular-spiking units in layer 5 of the mouse forelimb M1 during an M1-dependent, sensory-triggered reaching task. PV+ neurons showed short latency responses to the acoustic cue and vibrotactile trigger stimulus and an increase in firing at reaching onset that scaled with the amplitude of reaching. Unexpectedly, PV+ neurons fired before regular-spiking units at reach onset and showed high overall firing rates during both sensory-triggered and spontaneous reaches. Our data suggest that increasing M1 PV+ neuron firing rates may play a role in the initiation of voluntary reaching.


Assuntos
Neurônios GABAérgicos/metabolismo , Córtex Motor/metabolismo , Parvalbuminas/metabolismo , Potenciais de Ação/fisiologia , Animais , Potenciais Pós-Sinápticos Excitadores/fisiologia , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL
2.
Nat Neurosci ; 20(2): 209-218, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27941788

RESUMO

The skin is equipped with specialized mechanoreceptors that allow the perception of the slightest brush. Indeed, some mechanoreceptors can detect even nanometer-scale movements. Movement is transformed into electrical signals via the gating of mechanically activated ion channels at sensory endings in the skin. The sensitivity of Piezo mechanically gated ion channels is controlled by stomatin-like protein-3 (STOML3), which is required for normal mechanoreceptor function. Here we identify small-molecule inhibitors of STOML3 oligomerization that reversibly reduce the sensitivity of mechanically gated currents in sensory neurons and silence mechanoreceptors in vivo. STOML3 inhibitors in the skin also reversibly attenuate fine touch perception in normal mice. Under pathophysiological conditions following nerve injury or diabetic neuropathy, the slightest touch can produce pain, and here STOML3 inhibitors can reverse mechanical hypersensitivity. Thus, small molecules applied locally to the skin can be used to modulate touch and may represent peripherally available drugs to treat tactile-driven pain following neuropathy.


Assuntos
Hipersensibilidade/metabolismo , Canais Iônicos/metabolismo , Mecanorreceptores/metabolismo , Proteínas de Membrana/antagonistas & inibidores , Proteínas do Tecido Nervoso/antagonistas & inibidores , Células Receptoras Sensoriais/metabolismo , Animais , Gânglios Espinais/metabolismo , Hipersensibilidade/tratamento farmacológico , Mecanotransdução Celular/efeitos dos fármacos , Mecanotransdução Celular/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/metabolismo , Células Receptoras Sensoriais/efeitos dos fármacos , Pele/inervação , Tato/fisiologia
3.
J Virol Methods ; 168(1-2): 63-71, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20433869

RESUMO

A quantitative real-time reverse transcriptase PCR (RT-qPCR) assay was developed for the analysis of influenza A virus transcription and replication dynamics in mammalian cell culture. The assay is based on a polarity- and sequence-specific reverse transcription used to distinguish specifically between viral genomes (vRNA(-)), replicative intermediates (cRNA(+)) and viral messenger RNAs (vmRNA(+)) of segments 4 (HA), 6 (NA), 7 (M) and 8 (NS) during the life cycle of influenza virus. Synthetic viral RNAs used as reference standards for validation and quantitation were prepared for each viral RNA type and segment. Assay validation demonstrated linearity over five orders of magnitude, sensitivity of 1.0 x 10(3) to 8.9 x 10(3) of viral RNA molecules, repeatability and reproducibility of less than 0.8-3.1% CV (coefficient of variation). Dynamics of influenza A virus infection in adherent MDCK cells, a substrate considered for human influenza vaccine manufacturing, were analyzed. In general, mainly vmRNA(+) were synthesized during early phases of infection at about 0.6 hpi, followed immediately by cRNA(+) synthesis and after a short delay of about 1.9 hpi viral genome replication could be detected. The vRNA(-)s were synthesized in equimolar amounts and similar dynamics whereas preferential synthesis of NS1 vmRNA(+) in early transcription phases and a delay for M1 vmRNA(+) was found.


Assuntos
Perfilação da Expressão Gênica , Vírus da Influenza A/fisiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transcrição Gênica , Replicação Viral , Animais , Células Cultivadas , Cães , Vírus da Influenza A/genética , Vírus da Influenza A/crescimento & desenvolvimento , RNA Viral/biossíntese , RNA Viral/genética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
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