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1.
Nat Commun ; 12(1): 5245, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34475396

RESUMO

State-of-the-art silicon probes for electrical recording from neurons have thousands of recording sites. However, due to volume limitations there are typically many fewer wires carrying signals off the probe, which restricts the number of channels that can be recorded simultaneously. To overcome this fundamental constraint, we propose a method called electrode pooling that uses a single wire to serve many recording sites through a set of controllable switches. Here we present the framework behind this method and an experimental strategy to support it. We then demonstrate its feasibility by implementing electrode pooling on the Neuropixels 1.0 electrode array and characterizing its effect on signal and noise. Finally we use simulations to explore the conditions under which electrode pooling saves wires without compromising the content of the recordings. We make recommendations on the design of future devices to take advantage of this strategy.


Assuntos
Eletrodos Implantados , Eletrofisiologia/métodos , Espaço Extracelular/fisiologia , Silício/química , Potenciais de Ação , Animais , Encéfalo/fisiologia , Eletrofisiologia/instrumentação , Desenho de Equipamento , Camundongos , Rede Nervosa/fisiologia , Neurônios/fisiologia , Processamento de Sinais Assistido por Computador
2.
Nat Commun ; 12(1): 4911, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389710

RESUMO

The mammalian sensory neocortex consists of hierarchically organized areas reciprocally connected via feedforward (FF) and feedback (FB) circuits. Several theories of hierarchical computation ascribe the bulk of the computational work of the cortex to looped FF-FB circuits between pairs of cortical areas. However, whether such corticocortical loops exist remains unclear. In higher mammals, individual FF-projection neurons send afferents almost exclusively to a single higher-level area. However, it is unclear whether FB-projection neurons show similar area-specificity, and whether they influence FF-projection neurons directly or indirectly. Using viral-mediated monosynaptic circuit tracing in macaque primary visual cortex (V1), we show that V1 neurons sending FF projections to area V2 receive monosynaptic FB inputs from V2, but not other V1-projecting areas. We also find monosynaptic FB-to-FB neuron contacts as a second motif of FB connectivity. Our results support the existence of FF-FB loops in primate cortex, and suggest that FB can rapidly and selectively influence the activity of incoming FF signals.


Assuntos
Biorretroalimentação Psicológica/fisiologia , Macaca fascicularis/fisiologia , Neurônios/fisiologia , Córtex Visual/fisiologia , Vias Visuais/fisiologia , Animais , Feminino , Corpos Geniculados/citologia , Corpos Geniculados/fisiologia , Modelos Neurológicos , Reflexo Monosináptico/fisiologia , Córtex Visual/citologia
4.
Nat Commun ; 12(1): 4839, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376673

RESUMO

The ability to maintain a sequence of items in memory is a fundamental cognitive function. In the rodent hippocampus, the representation of sequentially organized spatial locations is reflected by the phase of action potentials relative to the theta oscillation (phase precession). We investigated whether the timing of neuronal activity relative to the theta brain oscillation also reflects sequence order in the medial temporal lobe of humans. We used a task in which human participants learned a fixed sequence of pictures and recorded single neuron and local field potential activity with implanted electrodes. We report that spikes for three consecutive items in the sequence (the preferred stimulus for each cell, as well as the stimuli immediately preceding and following it) were phase-locked at distinct phases of the theta oscillation. Consistent with phase precession, spikes were fired at progressively earlier phases as the sequence advanced. These findings generalize previous findings in the rodent hippocampus to the human temporal lobe and suggest that encoding stimulus information at distinct oscillatory phases may play a role in maintaining sequential order in memory.


Assuntos
Potenciais de Ação/fisiologia , Epilepsia/fisiopatologia , Aprendizagem/fisiologia , Neurônios/fisiologia , Ritmo Teta/fisiologia , Adolescente , Adulto , Epilepsia/diagnóstico , Feminino , Hipocampo/citologia , Hipocampo/fisiologia , Humanos , Masculino , Modelos Neurológicos , Neurônios/citologia , Estimulação Luminosa/métodos , Lobo Temporal/citologia , Lobo Temporal/fisiologia , Adulto Jovem
5.
Nat Commun ; 12(1): 4830, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376663

RESUMO

Choice-relevant brain regions in prefrontal cortex may progressively transform information about options into choices. Here, we examine responses of neurons in four regions of the medial prefrontal cortex as macaques performed two-option risky choices. All four regions encode economic variables in similar proportions and show similar putative signatures of key choice-related computations. We provide evidence to support a gradient of function that proceeds from areas 14 to 25 to 32 to 24. Specifically, we show that decodability of twelve distinct task variables increases along that path, consistent with the idea that regions that are higher in the anatomical hierarchy make choice-relevant variables more separable. We also show progressively longer intrinsic timescales in the same series. Together these results highlight the importance of the medial wall in choice, endorse a specific gradient-based organization, and argue against a modular functional neuroanatomy of choice.


Assuntos
Comportamento de Escolha/fisiologia , Macaca mulatta/fisiologia , Neurônios/fisiologia , Córtex Pré-Frontal/fisiologia , Potenciais de Ação/fisiologia , Algoritmos , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologia , Mapeamento Encefálico , Imageamento por Ressonância Magnética/métodos , Modelos Neurológicos , Córtex Pré-Frontal/citologia
6.
Theranostics ; 11(16): 7685-7699, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335958

RESUMO

Rationale: Mild traumatic brain injury (mTBI), the most common type of brain trauma, frequently leads to chronic cognitive and neurobehavioral deficits. Intervening effectively is impeded by our poor understanding of its pathophysiological sequelae. Methods: To elucidate the long-term neurovascular sequelae of mTBI, we combined optogenetics, two-photon fluorescence microscopy, and intracortical electrophysiological recordings in mice to selectively stimulate peri-contusional neurons weeks following repeated closed-head injury and probe individual vessel's function and local neuronal reactivity. Results: Compared to sham-operated animals, mTBI mice showed doubled cortical venular speeds (115 ± 25%) and strongly elevated cortical venular reactivity (53 ± 17%). Concomitantly, the pericontusional neurons exhibited attenuated spontaneous activity (-57 ± 79%) and decreased reactivity (-47 ± 28%). Post-mortem immunofluorescence revealed signs of peri-contusional senescence and DNA damage, in the absence of neuronal loss or gliosis. Alteration of neuronal and vascular functioning was largely prevented by chronic, low dose, systemic administration of a GABA-A receptor inverse agonist (L-655,708), commencing 3 days following the third impact. Conclusions: Our findings indicate that repeated mTBI leads to dramatic changes in the neurovascular unit function and that attenuation of tonic inhibition can prevent these alterations. The sustained disruption of the neurovascular function may underlie the concussed brain's long-term susceptibility to injury, and calls for development of better functional assays as well as of neurovascularly targeted interventions.


Assuntos
Concussão Encefálica/metabolismo , Concussão Encefálica/fisiopatologia , Acoplamento Neurovascular/fisiologia , Animais , Encéfalo/fisiopatologia , Modelos Animais de Doenças , Feminino , Masculino , Camundongos , Camundongos Endogâmicos , Microscopia de Fluorescência/métodos , Neurônios/fisiologia , Optogenética/métodos
7.
Nat Commun ; 12(1): 4767, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34362912

RESUMO

Axons in the cerebral cortex show a broad range of myelin coverage. Oligodendrocytes establish this pattern by selecting a cohort of axons for myelination; however, the distribution of myelin on distinct neurons and extent of internode replacement after demyelination remain to be defined. Here we show that myelination patterns of seven distinct neuron subtypes in somatosensory cortex are influenced by both axon diameter and neuronal identity. Preference for myelination of parvalbumin interneurons was preserved between cortical areas with varying myelin density, suggesting that regional differences in myelin abundance arises through local control of oligodendrogenesis. By imaging loss and regeneration of myelin sheaths in vivo we show that myelin distribution on individual axons was altered but overall myelin content on distinct neuron subtypes was restored. Our findings suggest that local changes in myelination are tolerated, allowing regenerated oligodendrocytes to restore myelin content on distinct neurons through opportunistic selection of axons.


Assuntos
Encéfalo/fisiologia , Córtex Cerebral/fisiologia , Bainha de Mielina/fisiologia , Neurônios/fisiologia , Regeneração/fisiologia , Animais , Axônios/fisiologia , Feminino , Interneurônios/fisiologia , Masculino , Camundongos , Oligodendroglia , Organogênese/fisiologia , Parvalbuminas , Córtex Somatossensorial
8.
Nat Commun ; 12(1): 4795, 2021 08 09.
Artigo em Inglês | MEDLINE | ID: mdl-34373460

RESUMO

Chemogenetic and optogenetic tools have transformed the field of neuroscience by facilitating the examination and manipulation of existing circuits. Yet, the field lacks tools that enable rational rewiring of circuits via the creation or modification of synaptic relationships. Here we report the development of HySyn, a system designed to reconnect neural circuits in vivo by reconstituting synthetic modulatory neurotransmission. We demonstrate that genetically targeted expression of the two HySyn components, a Hydra-derived neuropeptide and its receptor, creates de novo neuromodulatory transmission in a mammalian neuronal tissue culture model and functionally rewires a behavioral circuit in vivo in the nematode Caenorhabditis elegans. HySyn can interface with existing optogenetic, chemogenetic and pharmacological approaches to functionally probe synaptic transmission, dissect neuropeptide signaling, or achieve targeted modulation of specific neural circuits and behaviors.


Assuntos
Neurônios/fisiologia , Transmissão Sináptica/genética , Transmissão Sináptica/fisiologia , Animais , Comportamento Animal/fisiologia , Caenorhabditis elegans/genética , Caenorhabditis elegans/fisiologia , Cálcio , Expressão Gênica , Técnicas Genéticas , Hydra/genética , Hydra/fisiologia , Vias Neurais/fisiologia , Neuropeptídeos , Optogenética , Transdução de Sinais
9.
Eur J Endocrinol ; 185(4): R93-R101, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34370694

RESUMO

In 2008, the first evidence of a new hormone called neuronostatin was published. The hormone was discovered using a bioinformatic method and found to originate from the same preprohormone as somatostatin. This small peptide hormone of 13 amino acids and a C-terminal amidation was soon found to exert pleiotropic physiological effects. In animal studies, neuronostatin has been shown to reduce food intake and delay gastric emptying and gastrointestinal transit. Furthermore, neuronostatin has been shown to affect glucose metabolism by increasing glucagon secretion during situations when glucose concentrations are low. Additionally, neuronostatin has been shown to affect neural tissue and cardiomyocytes by suppressing cardiac contractility. The effects of neuronostatin have not yet been delineated in humans, but if the effects found in animal studies translate to humans it could position neuronostatin as a promising target in the treatment of obesity, hypertension and diabetes. In this review, we describe the discovery of neuronostatin and the current understanding of its physiological role and potential therapeutic applicability.


Assuntos
Hormônios Peptídicos/fisiologia , Animais , Regulação do Apetite/efeitos dos fármacos , Regulação do Apetite/genética , Diabetes Mellitus/genética , Diabetes Mellitus/terapia , Esvaziamento Gástrico/efeitos dos fármacos , Esvaziamento Gástrico/genética , Humanos , Hipertensão/genética , Hipertensão/terapia , Contração Muscular/efeitos dos fármacos , Contração Muscular/genética , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Obesidade/genética , Obesidade/terapia , Hormônios Peptídicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Somatostatina/química , Somatostatina/farmacologia , Somatostatina/fisiologia
10.
Oxid Med Cell Longev ; 2021: 5481228, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34457114

RESUMO

Peripheral nerve injury (PNI), resulting in the impairment of myelin sheaths and axons, seriously affects the transmission of sensory or motor nerves. Growth factors (GFs) provide a biological microenvironment for supporting nerve regrowth and have become a promising alternative for repairing PNI. As one number of intracellular growth factor family, fibroblast growth factor 13 (FGF13) was regard as a microtubule-stabilizing protein for regulating cytoskeletal plasticity and neuronal polarization. However, the therapeutic efficiency and underlying mechanism of FGF13 for treating PNI remained unknown. Here, the application of lentivirus that overexpressed FGF13 was delivered directly to the lesion site of transverse sciatic nerve for promoting peripheral nerve regeneration. Through behavioral analysis and histological and ultrastructure examinations, we found that FGF13 not only facilitated motor and sense functional recovery but also enhanced axon elongation and remyelination. Furthermore, pretreatment with FGF13 also promoted Schwann cell (SC) viability and upregulated the expression cellular microtubule-associated proteins in vitro PNI model. These data indicated FGF13 therapeutic effect was closely related to maintain cellular microtubule stability. Thus, this work provides the evident that FGF13-medicated microtubule stability is necessary for promoting peripheral nerve repair following PNI, highlighting the potential therapeutic value of FGF13 on ameliorating injured nerve recovery.


Assuntos
Fatores de Crescimento de Fibroblastos/metabolismo , Microtúbulos/química , Regeneração Nervosa , Neurônios/citologia , Traumatismos dos Nervos Periféricos/terapia , Recuperação de Função Fisiológica , Células de Schwann/citologia , Animais , Fatores de Crescimento de Fibroblastos/genética , Masculino , Neurônios/fisiologia , Traumatismos dos Nervos Periféricos/etiologia , Traumatismos dos Nervos Periféricos/patologia , Ratos , Ratos Sprague-Dawley , Células de Schwann/fisiologia
11.
Zoolog Sci ; 38(4): 317-325, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34342952

RESUMO

Many insects in temperate regions avoid environmental adversity for reproduction, and thus enter reproductive diapause according to photoperiod. This reproductive diapause is induced by inhibition of juvenile hormone biosynthesis in the corpus allatum. Some neuropeptides that have an effect on juvenile hormone biosynthesis have been detected in insect brains. Thus, the reproductive diapause may be photoperiodically regulated by these juvenile hormones-controlling neuropeptides. However, there is limited understanding of how the neurons expressing these neuropeptides respond to the photoperiod and control the peptide release accordingly. Here, we performed electrophysiological analyses in the pars intercerebralis (PI) of Plautia stali, where juvenile hormone inhibitory neuropeptides, Plautia stali myoinhibitory peptides (Plast-MIPs) are expressed. We found that the large neurons in the PI showed very high firing activity under diapause-inducing short day conditions. Neurotracer staining revealed that all recorded neurons projected to the nervus corporis cardiaci 1, which is known to be connected to the corpus cardiacum-corpus allatum complex. Finally, we determined how many of the large PI cells expressed Plast-MIP by single cell reverse transcription PCR. About half of large PI neurons coexpressed Plast-Mip and other neuropeptides, Diuretic hormone 44 and insulin-like peptide 1. The remaining cells only expressed Diuretic hormone 44 and insulin-like peptide 1. The present results suggested that large PI neurons, including Plast-MIP neurons, have enhanced activity under short day conditions, which may increase Plast-MIP release to the corpus cardiacum-corpus allatum complex and thus contribute to reproductive diapause.


Assuntos
Heterópteros/fisiologia , Fotoperíodo , Animais , Encéfalo/citologia , Diapausa , Feminino , Regulação da Expressão Gênica/fisiologia , Regulação da Expressão Gênica/efeitos da radiação , Neurônios/fisiologia , Neuropeptídeos/genética , Neuropeptídeos/metabolismo
12.
Phys Rev Lett ; 127(3): 038301, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34328756

RESUMO

Lorentzian distributions have been largely employed in statistical mechanics to obtain exact results for heterogeneous systems. Analytic continuation of these results is impossible even for slightly deformed Lorentzian distributions due to the divergence of all the moments (cumulants). We have solved this problem by introducing a "pseudocumulants" expansion. This allows us to develop a reduction methodology for heterogeneous spiking neural networks subject to extrinsic and endogenous fluctuations, thus obtaining a unified mean-field formulation encompassing quenched and dynamical sources of disorder.


Assuntos
Modelos Neurológicos , Modelos Estatísticos , Neurônios/fisiologia , Potenciais de Ação , Dinâmica Populacional
13.
Neuron ; 109(16): 2556-2572.e6, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34197732

RESUMO

Neurological and psychiatric disorders are associated with pathological neural dynamics. The fundamental connectivity patterns of cell-cell communication networks that enable pathological dynamics to emerge remain unknown. Here, we studied epileptic circuits using a newly developed computational pipeline that leveraged single-cell calcium imaging of larval zebrafish and chronically epileptic mice, biologically constrained effective connectivity modeling, and higher-order motif-focused network analysis. We uncovered a novel functional cell type that preferentially emerged in the preseizure state, the superhub, that was unusually richly connected to the rest of the network through feedforward motifs, critically enhancing downstream excitation. Perturbation simulations indicated that disconnecting superhubs was significantly more effective in stabilizing epileptic circuits than disconnecting hub cells that were defined traditionally by connection count. In the dentate gyrus of chronically epileptic mice, superhubs were predominately modeled adult-born granule cells. Collectively, these results predict a new maximally selective and minimally invasive cellular target for seizure control.


Assuntos
Comunicação Celular/fisiologia , Epilepsia/fisiopatologia , Neurônios/fisiologia , Convulsões/fisiopatologia , Animais , Giro Denteado/patologia , Giro Denteado/fisiopatologia , Rede Nervosa/fisiopatologia , Peixe-Zebra
14.
Neuron ; 109(16): 2519-2534, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34293296

RESUMO

Developing sensory circuits exhibit different patterns of spontaneous activity, patterns that are related to the construction and refinement of functional networks. During the development of different sensory modalities, spontaneous activity originates in the immature peripheral sensory structures and in the higher-order central structures, such as the thalamus and cortex. Certainly, the perinatal thalamus exhibits spontaneous calcium waves, a pattern of activity that is fundamental for the formation of sensory maps and for circuit plasticity. Here, we review our current understanding of the maturation of early (including embryonic) patterns of spontaneous activity and their influence on the assembly of thalamic and cortical sensory networks. Overall, the data currently available suggest similarities between the developmental trajectory of brain activity in experimental models and humans, which in the future may help to improve the early diagnosis of developmental disorders.


Assuntos
Potenciais de Ação/fisiologia , Córtex Cerebral/fisiologia , Plasticidade Neuronal/fisiologia , Córtex Somatossensorial/fisiologia , Animais , Humanos , Neurônios/fisiologia , Lobo Parietal/fisiologia
15.
Nat Commun ; 12(1): 4234, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244491

RESUMO

We propose a Double EXponential Adaptive Threshold (DEXAT) neuron model that improves the performance of neuromorphic Recurrent Spiking Neural Networks (RSNNs) by providing faster convergence, higher accuracy and a flexible long short-term memory. We present a hardware efficient methodology to realize the DEXAT neurons using tightly coupled circuit-device interactions and experimentally demonstrate the DEXAT neuron block using oxide based non-filamentary resistive switching devices. Using experimentally extracted parameters we simulate a full RSNN that achieves a classification accuracy of 96.1% on SMNIST dataset and 91% on Google Speech Commands (GSC) dataset. We also demonstrate full end-to-end real-time inference for speech recognition using real fabricated resistive memory circuit based DEXAT neurons. Finally, we investigate the impact of nanodevice variability and endurance illustrating the robustness of DEXAT based RSNNs.


Assuntos
Modelos Neurológicos , Redes Neurais de Computação , Neurônios/fisiologia , Computadores , Conjuntos de Dados como Assunto , Humanos , Nanoestruturas , Interface para o Reconhecimento da Fala
16.
Int J Mol Sci ; 22(14)2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34299127

RESUMO

Reelin is a secretory protein involved in a variety of processes in forebrain development and function, including neuronal migration, dendrite growth, spine formation, and synaptic plasticity. Most of the function of Reelin is focused on excitatory neurons; however, little is known about its effects on inhibitory neurons and inhibitory synapses. In this study, we investigated the phosphatidylinositol 3-kinase/Akt pathway of Reelin in primary cortical and hippocampal neurons. Individual neurons were visualized using immunofluorescence to distinguish inhibitory neurons from excitatory neurons. Reelin-rich protein supplementation significantly induced the phosphorylation of Akt and ribosomal S6 protein in excitatory neurons, but not in most inhibitory neurons. In somatostatin-expressing inhibitory neurons, one of major subtypes of inhibitory neurons, Reelin-rich protein supplementation induced the phosphorylation of S6. Subsequently, we investigated whether or not Reelin-rich protein supplementation affected dendrite development in cultured inhibitory neurons. Reelin-rich protein supplementation did not change the total length of dendrites in inhibitory neurons in vitro. Finally, we examined the development of inhibitory synapses in primary hippocampal neurons and found that Reelin-rich protein supplementation significantly reduced the density of gephyrin-VGAT-positive clusters in the dendritic regions without changing the expression levels of several inhibitory synapse-related proteins. These findings indicate a new role for Reelin in specific groups of inhibitory neurons and the development of inhibitory synapses, which may contribute to the underlying cellular mechanisms of RELN-associated neurological disorders.


Assuntos
Moléculas de Adesão Celular Neuronais/metabolismo , Dendritos/fisiologia , Proteínas da Matriz Extracelular/metabolismo , Potenciais Pós-Sinápticos Inibidores , Proteínas do Tecido Nervoso/metabolismo , Inibição Neural , Plasticidade Neuronal , Neurônios/fisiologia , Serina Endopeptidases/metabolismo , Sinapses/fisiologia , Animais , Moléculas de Adesão Celular Neuronais/genética , Proteínas da Matriz Extracelular/genética , Hipocampo/citologia , Hipocampo/fisiologia , Camundongos , Camundongos Endogâmicos ICR , Proteínas do Tecido Nervoso/genética , Neurogênese , Neurônios/citologia , Serina Endopeptidases/genética , Transdução de Sinais
18.
Int J Mol Sci ; 22(14)2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34299239

RESUMO

Estrogens are steroid hormones that play a crucial role in the regulation of the reproductive and non-reproductive system physiology. Among non-reproductive systems, the nervous system is mainly affected by estrogens due to their antioxidant, anti-apoptotic, and anti-inflammatory activities, which are mediated by membranous and nuclear estrogen receptors, and also by non-estrogen receptor-associated estrogen actions. Neuronal viability and functionality are also associated with the maintenance of mitochondrial functions. Recently, the localization of estrogen receptors, especially estrogen receptor beta, in the mitochondria of many types of neuronal cells is documented, indicating the direct involvement of the mitochondrial estrogen receptor beta (mtERß) in the maintenance of neuronal physiology. In this study, cell lines of N2A cells stably overexpressing a mitochondrial-targeted estrogen receptor beta were generated and further analyzed to study the direct involvement of mtERß in estrogen neuroprotective antioxidant and anti-apoptotic actions. Results from this study revealed that the presence of estrogen receptor beta in mitochondria render N2A cells more resistant to staurosporine- and H2O2-induced apoptotic stimuli, as indicated by the reduced activation of caspase-9 and -3, the increased cell viability, the increased ATP production, and the increased resistance to mitochondrial impairment in the presence or absence of 17-ß estradiol (E2). Thus, the direct involvement of mtERß in antioxidant and anti-apoptotic activities is documented, rendering mtERß a promising therapeutic target for mitochondrial dysfunction-associated degenerative diseases.


Assuntos
Receptor beta de Estrogênio/metabolismo , Mitocôndrias/metabolismo , Neuroblastoma/metabolismo , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Estradiol/farmacologia , Receptor beta de Estrogênio/genética , Estrogênios/metabolismo , Estrogênios/farmacologia , Peróxido de Hidrogênio/metabolismo , Camundongos , Mitocôndrias/fisiologia , Células-Tronco Neurais/metabolismo , Neuroblastoma/genética , Neurônios/metabolismo , Neurônios/fisiologia , Neuroproteção/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Receptores de Estrogênio/metabolismo
19.
Nat Commun ; 12(1): 4488, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301944

RESUMO

Opn7b is a non-visual G protein-coupled receptor expressed in zebrafish. Here we find that Opn7b expressed in HEK cells constitutively activates the Gi/o pathway and illumination with blue/green light inactivates G protein-coupled inwardly rectifying potassium channels. This suggests that light acts as an inverse agonist for Opn7b and can be used as an optogenetic tool to inhibit neuronal networks in the dark and interrupt constitutive inhibition in the light. Consistent with this prediction, illumination of recombinant expressed Opn7b in cortical pyramidal cells results in increased neuronal activity. In awake mice, light stimulation of Opn7b expressed in pyramidal cells of somatosensory cortex reliably induces generalized epileptiform activity within a short (<10 s) delay after onset of stimulation. Our study demonstrates a reversed mechanism for G protein-coupled receptor control and Opn7b as a tool for controlling neural circuit properties.


Assuntos
Proteínas de Ligação ao GTP/metabolismo , Neurônios/metabolismo , Opsinas/metabolismo , Optogenética/métodos , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Proteínas de Ligação ao GTP/genética , Células HEK293 , Humanos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Opsinas/genética , Células Piramidais/metabolismo , Células Piramidais/fisiologia , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/genética , Córtex Somatossensorial/citologia , Córtex Somatossensorial/metabolismo , Sinapses/genética , Sinapses/fisiologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/genética
20.
Commun Biol ; 4(1): 855, 2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244604

RESUMO

The spatial-temporal sequence of cerebral blood flow (CBF), cerebral blood volume (CBV) and blood velocity changes triggered by neuronal activation is critical for understanding functional brain imaging. This sequence follows a stereotypic pattern of changes across different zones of the vasculature in the olfactory bulb, the first relay of olfaction. However, in the cerebral cortex, where most human brain mapping studies are performed, the timing of activity evoked vascular events remains controversial. Here we utilized a single whisker stimulation model to map out functional hyperemia along vascular arbours from layer II/III to the surface of primary somatosensory cortex, in anesthetized and awake Thy1-GCaMP6 mice. We demonstrate that sensory stimulation triggers an increase in blood velocity within the mid-capillary bed and a dilation of upstream large capillaries, and the penetrating and pial arterioles. We report that under physiological stimulation, response onset times are highly variable across compartments of different vascular arbours. Furthermore, generating transfer functions (TFs) between neuronal Ca2+ and vascular dynamics across different brain states demonstrates that anesthesia decelerates neurovascular coupling (NVC). This spatial-temporal pattern of vascular events demonstrates functional diversity not only between different brain regions but also at the level of different vascular arbours within supragranular layers of the cerebral cortex.


Assuntos
Encéfalo/fisiologia , Córtex Cerebral/fisiologia , Circulação Cerebrovascular/fisiologia , Acoplamento Neurovascular/fisiologia , Córtex Somatossensorial/fisiologia , Animais , Encéfalo/irrigação sanguínea , Mapeamento Encefálico/métodos , Capilares/fisiologia , Córtex Cerebral/irrigação sanguínea , Feminino , Humanos , Masculino , Camundongos Endogâmicos C57BL , Neuroimagem/métodos , Neurônios/fisiologia , Bulbo Olfatório/irrigação sanguínea , Bulbo Olfatório/fisiologia , Córtex Somatossensorial/irrigação sanguínea , Vibrissas/fisiologia , Vigília/fisiologia
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