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1.
Adv Exp Med Biol ; 1131: 73-91, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31646507

RESUMO

Imaging techniques may overcome the limitations of electrode techniques to measure locally not only membrane potential changes, but also ionic currents. Here, we review a recently developed approach to image native neuronal Ca2+ currents from brain slices. The technique is based on combined fluorescence recordings using low-affinity Ca2+ indicators possibly in combination with voltage sensitive dyes. We illustrate how the kinetics of a Ca2+ current can be estimated from the Ca2+ fluorescence change and locally correlated with the change of membrane potential, calibrated on an absolute scale, from the voltage fluorescence change. We show some representative measurements from the dendrites of CA1 hippocampal pyramidal neurons, from olfactory bulb mitral cells and from cerebellar Purkinje neurons. We discuss the striking difference in data analysis and interpretation between Ca2+ current measurements obtained using classical electrode techniques and the physiological currents obtained using this novel approach. Finally, we show how important is the kinetic information on the native Ca2+ current to explore the potential molecular targets of the Ca2+ flux from each individual Ca2+ channel.


Assuntos
Canais de Cálcio , Neuroimagem , Animais , Cálcio/metabolismo , Canais de Cálcio/fisiologia , Dendritos/fisiologia , Humanos , Potenciais da Membrana/fisiologia , Imagem Óptica , Células Piramidais/fisiologia
2.
Neuron ; 103(1): 118-132.e7, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31147153

RESUMO

Animals use global image motion cues to actively stabilize their position by compensatory movements. Neurons in the zebrafish pretectum distinguish different optic flow patterns, e.g., rotation and translation, to drive appropriate behaviors. Combining functional imaging and morphological reconstruction of single cells, we revealed critical neuroanatomical features of this sensorimotor transformation. Terminals of direction-selective retinal ganglion cells (DS-RGCs) are located within the pretectal retinal arborization field 5 (AF5), where they meet dendrites of pretectal neurons with simple tuning to monocular optic flow. Translation-selective neurons, which respond selectively to optic flow in the same direction for both eyes, are intermingled with these simple cells but do not receive inputs from DS-RGCs. Mutually exclusive populations of pretectal projection neurons innervate either the reticular formation or the cerebellum, which in turn control motor responses. We posit that local computations in a defined pretectal circuit transform optic flow signals into neural commands driving optomotor behavior. VIDEO ABSTRACT.


Assuntos
Fluxo Óptico/fisiologia , Vias Visuais/citologia , Animais , Cerebelo/citologia , Cerebelo/fisiologia , Dendritos/fisiologia , Neurópilo/fisiologia , Neurópilo/ultraestrutura , Terminações Pré-Sinápticas/fisiologia , Formação Reticular/citologia , Formação Reticular/fisiologia , Células Ganglionares da Retina/fisiologia , Colículos Superiores/citologia , Colículos Superiores/fisiologia , Visão Binocular/fisiologia , Visão Monocular/fisiologia , Vias Visuais/anatomia & histologia , Peixe-Zebra/fisiologia
3.
Neuron ; 103(2): 235-241.e4, 2019 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-31178115

RESUMO

Dendritic integration can expand the information-processing capabilities of neurons. However, the recruitment of active dendritic processing in vivo and its relationship to somatic activity remain poorly understood. Here, we use two-photon GCaMP6f imaging to simultaneously monitor dendritic and somatic compartments in the awake primary visual cortex. Activity in layer 5 pyramidal neuron somata and distal apical trunk dendrites shows surprisingly high functional correlation. This strong coupling persists across neural activity levels and is unchanged by visual stimuli and locomotion. Ex vivo combined somato-dendritic patch-clamp and GCaMP6f recordings indicate that dendritic signals specifically reflect local electrogenesis triggered by dendritic inputs or high-frequency bursts of somatic action potentials. In contrast to the view that dendrites are only sparsely recruited under highly specific conditions in vivo, our results provide evidence that active dendritic integration is a widespread and intrinsic feature of cortical computation.


Assuntos
Potenciais de Ação/fisiologia , Cálcio/metabolismo , Dendritos/fisiologia , Córtex Visual/citologia , Córtex Visual/fisiologia , Animais , Técnicas In Vitro , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Optogenética , Técnicas de Patch-Clamp , Estimulação Luminosa , Células Piramidais , Proteínas Plasmáticas de Ligação ao Retinol/genética , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo
4.
Neuron ; 103(4): 673-685.e5, 2019 08 21.
Artigo em Inglês | MEDLINE | ID: mdl-31230762

RESUMO

Autism spectrum disorder (ASD) is strongly associated with de novo gene mutations. One of the most commonly affected genes is SCN2A. ASD-associated SCN2A mutations impair the encoded protein NaV1.2, a sodium channel important for action potential initiation and propagation in developing excitatory cortical neurons. The link between an axonal sodium channel and ASD, a disorder typically attributed to synaptic or transcriptional dysfunction, is unclear. Here we show that NaV1.2 is unexpectedly critical for dendritic excitability and synaptic function in mature pyramidal neurons in addition to regulating early developmental axonal excitability. NaV1.2 loss reduced action potential backpropagation into dendrites, impairing synaptic plasticity and synaptic strength, even when NaV1.2 expression was disrupted in a cell-autonomous fashion late in development. These results reveal a novel dendritic function for NaV1.2, providing insight into cellular mechanisms probably underlying circuit and behavioral dysfunction in ASD.


Assuntos
Transtorno do Espectro Autista/genética , Dendritos/fisiologia , Córtex Pré-Frontal/fisiologia , Células Piramidais/fisiologia , Potenciais de Ação , Animais , Sinalização do Cálcio , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Heterozigoto , Hipocampo/citologia , Hipocampo/crescimento & desenvolvimento , Hipocampo/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Potenciais Pós-Sinápticos em Miniatura/fisiologia , N-Metilaspartato/análise , Neocórtex/citologia , Neocórtex/crescimento & desenvolvimento , Neocórtex/fisiologia , Córtex Pré-Frontal/citologia , Córtex Pré-Frontal/crescimento & desenvolvimento , Engenharia de Proteínas , Comportamento Social , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico/análise
5.
Genes Cells ; 24(7): 464-472, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31095815

RESUMO

Dendrites of neurons receive and process synaptic or sensory inputs. The Drosophila class IV dendritic arborization (da) neuron is an established model system to explore molecular mechanisms of dendrite morphogenesis. The total number of dendritic branch terminals is one of the frequently employed parameters to characterize dendritic arborization complexity of class IV neurons. This parameter gives a useful phenotypic readout of arborization during neurogenesis, and it is typically determined by laborious manual analyses of numerous images. Ideally, an automated analysis would greatly reduce the workload; however, it is challenging to automatically discriminate dendritic branch terminals from signals of surrounding tissues in whole-mount live larvae. Here, we describe our newly developed software, called DeTerm, which automatically recognizes and quantifies dendrite branch terminals via an artificial neural network. Once we input an image file of a neuronal dendritic arbor and its region of interest information, DeTerm is capable of labeling terminals of larval class IV neurons with high precision, and it also provides positional data of individual terminals. We further show that DeTerm is applicable to other types of neurons, including mouse cerebellar Purkinje cells. DeTerm is freely available on the web and was successfully tested on Mac, Windows and Linux.


Assuntos
Cerebelo/fisiologia , Dendritos/fisiologia , Redes Neurais (Computação) , Neurogênese , Neurônios/fisiologia , Células de Purkinje/fisiologia , Software , Animais , Cerebelo/citologia , Drosophila , Proteínas de Drosophila/metabolismo , Larva , Camundongos , Neurônios/citologia , Células de Purkinje/citologia
6.
PLoS Comput Biol ; 15(4): e1006974, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31009455

RESUMO

Transcranial brain stimulation and evidence of ephaptic coupling have sparked strong interests in understanding the effects of weak electric fields on the dynamics of neuronal populations. While their influence on the subthreshold membrane voltage can be biophysically well explained using spatially extended neuron models, mechanistic analyses of neuronal spiking and network activity have remained a methodological challenge. More generally, this challenge applies to phenomena for which single-compartment (point) neuron models are oversimplified. Here we employ a pyramidal neuron model that comprises two compartments, allowing to distinguish basal-somatic from apical dendritic inputs and accounting for an extracellular field in a biophysically minimalistic way. Using an analytical approach we fit its parameters to reproduce the response properties of a canonical, spatial model neuron and dissect the stochastic spiking dynamics of single cells and large networks. We show that oscillatory weak fields effectively mimic anti-correlated inputs at the soma and dendrite and strongly modulate neuronal spiking activity in a rather narrow frequency band. This effect carries over to coupled populations of pyramidal cells and inhibitory interneurons, boosting network-induced resonance in the beta and gamma frequency bands. Our work contributes a useful theoretical framework for mechanistic analyses of population dynamics going beyond point neuron models, and provides insights on modulation effects of extracellular fields due to the morphology of pyramidal cells.


Assuntos
Biologia Computacional/métodos , Estimulação Elétrica/métodos , Células Piramidais/fisiologia , Potenciais de Ação/fisiologia , Animais , Córtex Cerebral/fisiologia , Biologia Computacional/estatística & dados numéricos , Dendritos/fisiologia , Humanos , Interneurônios/fisiologia , Modelos Neurológicos , Neurônios/fisiologia
7.
Nat Commun ; 10(1): 1859, 2019 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-31015414

RESUMO

Complex spike bursts (CSBs) represent a characteristic firing pattern of hippocampal pyramidal cells (PCs). In CA1PCs, CSBs are driven by regenerative dendritic plateau potentials, produced by correlated entorhinal cortical and CA3 inputs that simultaneously depolarize distal and proximal dendritic domains. However, in CA3PCs neither the generation mechanisms nor the computational role of CSBs are well elucidated. We show that CSBs are induced by dendritic Ca2+ spikes in CA3PCs. Surprisingly, the ability of CA3PCs to produce CSBs is heterogeneous, with non-uniform synaptic input-output transformation rules triggering CSBs. The heterogeneity is partly related to the topographic position of CA3PCs; we identify two ion channel types, HCN and Kv2 channels, whose proximodistal activity gradients contribute to subregion-specific modulation of CSB propensity. Our results suggest that heterogeneous dendritic integrative properties, along with previously reported synaptic connectivity gradients, define functional subpopulations of CA3PCs that may support CA3 network computations underlying associative memory processes.


Assuntos
Potenciais de Ação/fisiologia , Região CA3 Hipocampal/fisiologia , Memória/fisiologia , Células Piramidais/fisiologia , Animais , Cálcio/metabolismo , Cátions Bivalentes/metabolismo , Dendritos/fisiologia , Masculino , Modelos Animais , Técnicas de Patch-Clamp , Ratos Wistar
8.
PLoS Comput Biol ; 15(3): e1006871, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30835719

RESUMO

The interplay between excitatory and inhibitory neurons imparts rich functions of the brain. To understand the synaptic mechanisms underlying neuronal computations, a fundamental approach is to study the dynamics of excitatory and inhibitory synaptic inputs of each neuron. The traditional method of determining input conductance, which has been applied for decades, employs the synaptic current-voltage (I-V) relation obtained via voltage clamp. Due to the space clamp effect, the measured conductance is different from the local conductance on the dendrites. Therefore, the interpretation of the measured conductance remains to be clarified. Using theoretical analysis, electrophysiological experiments, and realistic neuron simulations, here we demonstrate that there does not exist a transform between the local conductance and the conductance measured by the traditional method, due to the neglect of a nonlinear interaction between the clamp current and the synaptic current in the traditional method. Consequently, the conductance determined by the traditional method may not correlate with the local conductance on the dendrites, and its value could be unphysically negative as observed in experiment. To circumvent the challenge of the space clamp effect and elucidate synaptic impact on neuronal information processing, we propose the concept of effective conductance which is proportional to the local conductance on the dendrite and reflects directly the functional influence of synaptic inputs on somatic membrane potential dynamics, and we further develop a framework to determine the effective conductance accurately. Our work suggests re-examination of previous studies involving conductance measurement and provides a reliable approach to assess synaptic influence on neuronal computation.


Assuntos
Neurônios/fisiologia , Técnicas de Patch-Clamp , Transmissão Sináptica , Animais , Simulação por Computador , Dendritos/fisiologia , Hipocampo/citologia , Hipocampo/fisiologia , Potenciais da Membrana , Modelos Neurológicos , Ratos Sprague-Dawley
9.
PLoS Comput Biol ; 15(3): e1006757, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30840615

RESUMO

Dendrites of pyramidal cells exhibit complex morphologies and contain a variety of ionic conductances, which generate non-trivial integrative properties. Basal and proximal apical dendrites have been shown to function as independent computational subunits within a two-layer feedforward processing scheme. The outputs of the subunits are linearly summed and passed through a final non-linearity. It is an open question whether this mathematical abstraction can be applied to apical tuft dendrites as well. Using a detailed compartmental model of CA1 pyramidal neurons and a novel theoretical framework based on iso-response methods, we first show that somatic sub-threshold responses to brief synaptic inputs cannot be described by a two-layer feedforward model. Then, we relax the core assumption of subunit independence and introduce non-linear feedback from the output layer to the subunit inputs. We find that additive feedback alone explains the somatic responses to synaptic inputs to most of the branches in the apical tuft. Individual dendritic branches bidirectionally modulate the thresholds of their input-output curves without significantly changing the gains. In contrast to these findings for precisely timed inputs, we show that neuronal computations based on firing rates can be accurately described by purely feedforward two-layer models. Our findings support the view that dendrites of pyramidal neurons possess non-linear analog processing capabilities that critically depend on the location of synaptic inputs. The iso-response framework proposed in this computational study is highly efficient and could be directly applied to biological neurons.


Assuntos
Dendritos/fisiologia , Retroalimentação , Células Piramidais/fisiologia , Potenciais de Ação , Animais , Região CA1 Hipocampal/citologia , Modelos Biológicos , Sinapses/fisiologia
10.
J Physiol Sci ; 69(3): 453-463, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30758780

RESUMO

The neuronal K+-Cl- cotransporter KCC2 maintains a low intracellular Cl- concentration and facilitates hyperpolarizing GABAA receptor responses. KCC2 also plays a separate role in stabilizing and enhancing dendritic spines in the developing nervous system. Using a conditional transgenic mouse strategy, we examined whether overexpression of KCC2 enhances dendritic spines in the adult nervous system and characterized the effects on spine dynamics in the motor cortex in vivo during rotarod training. Mice overexpressing KCC2 showed significantly increased spine density in the apical dendrites of layer V pyramidal neurons, measured in vivo using two-photon imaging. During modest accelerated rotarod training, mice overexpressing KCC2 displayed enhanced spine formation rates, greater balancing skill at higher rotarod speeds and a faster rate of learning in this ability. Our results demonstrate that KCC2 enhances spine density and dynamics in the adult nervous system and suggest that KCC2 may play a role in experience-dependent synaptic plasticity.


Assuntos
Espinhas Dendríticas/metabolismo , Espinhas Dendríticas/fisiologia , Aprendizagem/fisiologia , Córtex Motor/metabolismo , Córtex Motor/fisiologia , Plasticidade Neuronal/fisiologia , Simportadores/metabolismo , Animais , Dendritos/metabolismo , Dendritos/fisiologia , Masculino , Camundongos , Camundongos Transgênicos , Células Piramidais/metabolismo , Células Piramidais/fisiologia , Sinapses/metabolismo , Sinapses/fisiologia
11.
J Agric Food Chem ; 67(9): 2709-2715, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30701967

RESUMO

Exposure to nanosized titanium oxide (nano-TiO2) has been proven to suppress brain growth in mouse offspring; however, whether retardation of axonal or dendritic outgrowth is associated with activation of the mitogen-activated protein kinase (MAPK) pathway remains unclear. In the present study, pregnant mice were exposed to nano-TiO2 at 1.25, 2.5, and 5 mg/kg body weight, and the molecular mechanism of axonal or dendritic outgrowth retardation was investigated. The results suggested that nano-TiO2 crossed the blood-fetal barrier and blood-brain barrier and deposited in the brain of offspring, which retarded axonal and dendritic outgrowth, including the absence of axonal outgrowth, and decreased dendritic filament length, dendritic branching number, and dendritic spine density. Importantly, maternal exposure to nano-TiO2 increased phosphorylated (p)-extracellular signal-regulated kinase1/2 (ERK1/2, +24.35% to +59.4%), p-p38 (+60.82% to 181.85%), and p-c-jun N-terminal kinase (JNK, +28.28% to 97.28%) expression in the hippocampus of the offspring. These findings suggested that retardation of axonal and dendritic outgrowth in mouse offspring caused by maternal exposure to nano-TiO2 may be related to excessive activation of the ERK1/2/MAPK signaling pathway. Therefore, the potential toxicity of nano-TiO2 is a concern, especially in pregnant woman or children who are exposed to nano-TiO2.


Assuntos
Axônios/efeitos dos fármacos , Dendritos/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Titânio/toxicidade , Animais , Axônios/fisiologia , Química Encefálica/efeitos dos fármacos , Dendritos/fisiologia , Feminino , Hipocampo/ultraestrutura , Troca Materno-Fetal , Camundongos , Nanopartículas , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Titânio/análise
12.
Neurosci Lett ; 698: 33-38, 2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30625349

RESUMO

Microglia are unique cells of the central nervous system (CNS) with a distinct ontogeny and molecular profile. They are the predominant immune resident cell in the CNS. Recent studies have revealed a diversity of transient and terminal physical interactions between microglia and neurons in the vertebrate brain. In this review, we follow the historical trail of the discovery of these interactions, summarize their notable features, provide implications of these discoveries to CNS function, emphasize emerging themes along the way and peak into the future of what outstanding questions remain to move the field forward.


Assuntos
Encéfalo/fisiologia , Microglia/fisiologia , Neurônios/fisiologia , Animais , Axônios/fisiologia , Encéfalo/citologia , Dendritos/fisiologia , Humanos , Fagocitose , Sinapses/fisiologia
13.
Science ; 363(6425): 413-417, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30679375

RESUMO

How neuronal connections are established and organized into functional networks determines brain function. In the mammalian cerebral cortex, different classes of GABAergic interneurons exhibit specific connectivity patterns that underlie their ability to shape temporal dynamics and information processing. Much progress has been made toward parsing interneuron diversity, yet the molecular mechanisms by which interneuron-specific connectivity motifs emerge remain unclear. In this study, we investigated transcriptional dynamics in different classes of interneurons during the formation of cortical inhibitory circuits in mouse. We found that whether interneurons form synapses on the dendrites, soma, or axon initial segment of pyramidal cells is determined by synaptic molecules that are expressed in a subtype-specific manner. Thus, cell-specific molecular programs that unfold during early postnatal development underlie the connectivity patterns of cortical interneurons.


Assuntos
Córtex Cerebral/fisiologia , Interneurônios/fisiologia , Sinapses/genética , Sinapses/fisiologia , Animais , Dendritos/genética , Dendritos/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Células Piramidais/fisiologia , Análise de Sequência de RNA , Transcrição Genética , Transcriptoma
14.
Mol Biol Cell ; 30(6): 742-752, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30699046

RESUMO

The regulation of organelle transport by the cytoskeleton is fundamental for eukaryotic survival. Cytoskeleton motors are typically modular proteins with conserved motor and diverse cargo-binding domains. Motor:cargo interactions are often indirect and mediated by adaptor proteins, for example, Rab GTPases. Rab27a, via effector melanophilin (Mlph), recruits myosin-Va (MyoVa) to melanosomes and thereby disperses them into melanocyte dendrites. To better understand how adaptors regulate motor:cargo interaction, we used single melanosome fluorescence recovery after photobleaching (smFRAP) to characterize the association kinetics among MyoVa, its adaptors, and melanosomes. We found that MyoVa and Mlph rapidly recovered after smFRAP, whereas Rab27a did not, indicating that MyoVa and Mlph dynamically associate with melanosomes and Rab27a does not. This suggests that dynamic Rab27a:effector interaction rather than Rab27a melanosome:cytosol cycling regulates MyoVa:melanosome association. Accordingly, a Mlph-Rab27a fusion protein reduced MyoVa smFRAP, indicating that it stabilized melanosomal MyoVa. Finally, we tested the functional importance of dynamic MyoVa:melanosome interaction. We found that whereas a MyoVa-Rab27a fusion protein dispersed melanosomes in MyoVa-deficient cells, dendrites were significantly less elongated than in wild-type cells. Given that dendrites are the prime sites of melanosome transfer from melanocytes to keratinocytes, we suggest that dynamic MyoVa:melanosome interaction is important for pigmentation in vivo.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Melanócitos/metabolismo , Cadeias Pesadas de Miosina/metabolismo , Miosina Tipo V/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Transporte Biológico/fisiologia , Técnicas de Cultura de Células , Citoesqueleto/metabolismo , Dendritos/metabolismo , Dendritos/fisiologia , Humanos , Melanócitos/fisiologia , Melanossomas/metabolismo , Camundongos , Ligação Proteica , Proteínas rab de Ligação ao GTP/metabolismo , Proteínas rab27 de Ligação ao GTP
15.
Neurochem Res ; 44(4): 917-929, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30656594

RESUMO

Increasing evidence suggests that exposure to chronic stress during adolescent period may lead to behavioral and neuronal morphology deficits in adulthood. This study examined whether crocin, the main active saffron constituent, and voluntary exercise, alone or combined, could prevent the detrimental influences of chronic restraint stress during adolescent (postnatal days, PND, 30-40) on behavioral and morphological deficits in adult (PND60) male rats. Results showed that plasma corticosterone levels increased at PND40, but not PND60 in stressed rats. Moreover, stressed rats demonstrated enhanced anxiety levels and depression like behaviors in adulthood. These behavioral abnormalities were accompanied by a decline in apical dendritic length in both infralimbic and prelimbic regions and dendritic branches in infralimbic region of the prefrontal cortex. Treatment with crocin, exposure to wheel running activity, and the combined interventions alleviated both behavioral and morphological deficits induced by adolescent stress. Moreover, these treatments exerted positive neuronal morphological effects in the prefrontal cortex in non-stressed animals. Our findings provide important evidences that exercise as a non-pharmacological intervention and crocin treatment during pre-pubertal period can protect against adolescent stress induced behavioral and morphological abnormalities in adulthood.


Assuntos
Ansiedade/terapia , Carotenoides/administração & dosagem , Dendritos/efeitos dos fármacos , Depressão/terapia , Condicionamento Físico Animal/métodos , Estresse Psicológico/terapia , Animais , Ansiedade/sangue , Terapia Combinada/métodos , Corticosterona/sangue , Dendritos/patologia , Dendritos/fisiologia , Depressão/sangue , Depressão/patologia , Masculino , Condicionamento Físico Animal/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/patologia , Córtex Pré-Frontal/fisiologia , Ratos , Ratos Wistar , Restrição Física , Estresse Psicológico/sangue , Estresse Psicológico/patologia , Resultado do Tratamento
16.
Neuron ; 101(3): 486-499.e4, 2019 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-30594427

RESUMO

The ascending cholinergic system dynamically regulates sensory perception and cognitive function, but it remains unclear how this modulation is executed in neocortical circuits. Here, we demonstrate that the cholinergic system controls the integrative operations of neocortical principal neurons by modulating dendritic excitability. Direct dendritic recordings revealed that the optogenetic-evoked release of acetylcholine (ACh) transformed the pattern of dendritic integration in layer 5B pyramidal neurons, leading to the generation of dendritic plateau potentials which powerfully drove repetitive action potential output. In contrast, the synaptic release of ACh did not positively modulate axo-somatic excitability. Mechanistically, the transformation of dendritic integration was mediated by the muscarinic ACh receptor-dependent enhancement of dendritic R-type calcium channel activity, a compartment-dependent modulation which decisively controlled the associative computations executed by layer 5B pyramidal neurons. Our findings therefore reveal a biophysical mechanism by which the cholinergic system controls dendritic computations causally linked to perceptual detection.


Assuntos
Potenciais de Ação , Neurônios Colinérgicos/fisiologia , Dendritos/fisiologia , Potenciais Pós-Sinápticos Excitadores , Neocórtex/fisiologia , Células Piramidais/fisiologia , Acetilcolina/metabolismo , Animais , Canais de Cálcio Tipo R/metabolismo , Neurônios Colinérgicos/metabolismo , Dendritos/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neocórtex/citologia , Neocórtex/metabolismo , Células Piramidais/metabolismo , Ratos , Ratos Wistar , Receptores Muscarínicos/metabolismo
17.
Dev Cell ; 48(2): 215-228.e5, 2019 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-30555000

RESUMO

Neurite fasciculation through contact-dependent signaling is important for the wiring and function of the neuronal circuits. Here, we describe a type of axon-dendrite fasciculation in C. elegans, where proximal dendrites of the nociceptor PVD adhere to the axon of the ALA interneuron. This axon-dendrite fasciculation is mediated by a previously uncharacterized adhesive signaling by the ALA membrane signal SAX-7/L1CAM and the PVD receptor SAX-3/Robo but independent of Slit. L1CAM physically interacts with Robo and instructs dendrite adhesion in a Robo-dependent manner. Fasciculation mediated by L1CAM-Robo signaling aligns F-actin dynamics in the dendrite growth cone and facilitates dynamic growth cone behaviors for efficient dendrite guidance. Disruption of PVD dendrite fasciculation impairs nociceptive mechanosensation and rhythmicity in body curvature, suggesting that dendrite fasciculation governs the functions of mechanosensory circuits. Our work elucidates the molecular mechanisms by which adhesive axon-dendrite signaling shapes the construction and function of sensory neuronal circuits.


Assuntos
Citoesqueleto de Actina/metabolismo , Fasciculação Axônica/fisiologia , Cones de Crescimento/metabolismo , Molécula L1 de Adesão de Célula Nervosa/metabolismo , Actinas/metabolismo , Animais , Axônios/metabolismo , Caenorhabditis elegans/crescimento & desenvolvimento , Proteínas de Caenorhabditis elegans , Citoesqueleto/metabolismo , Dendritos/fisiologia , Proteínas do Tecido Nervoso/metabolismo , Receptores Imunológicos/metabolismo
18.
Front Biosci (Landmark Ed) ; 24: 291-302, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30468656

RESUMO

Accumulating evidence suggests that the diabetes-induced cognitive dysfunction can be alleviated when exposed to the enriched environment. However, the impact of the changes of the hippocampal plasticity on the cognitive decline and the possible effect of an enriched environment in prediabetes are still not clearly documented. To explore the effect of enriched environment for prediabetes-induced changes of dendritic structural plasticity in hippocampus pyramidal and cognitive deficits, the praxiology experiments for evaluating of anxiety, spatial learning and memory of prediabetic Wistar were performed, and then the dendritic spine density was assessed in the hippocampal CA1 pyramidal neuronal region. The prediabetic rats demonstrated a hyper-anxiety like behavior and significantly decreased spatial learning abilities and memory deficits. Exposing prediabetic rats to an enriched environment appeared to significantly mitigate the above changes in a time-dependent manner. The enriched environment also restored the density of the hippocampal dendritic spine which was significantly reduced in prediabetic rats. We found that the enriched environment was beneficial in overcoming the prediabetes-induced cognitive disorders and diminished dendritic plasticity of hippocampus pyramidal.


Assuntos
Dendritos/fisiologia , Plasticidade Neuronal/fisiologia , Estado Pré-Diabético/fisiopatologia , Células Piramidais/fisiologia , Animais , Ansiedade/fisiopatologia , Glicemia/metabolismo , Região CA1 Hipocampal/citologia , Região CA1 Hipocampal/fisiopatologia , Disfunção Cognitiva/fisiopatologia , Masculino , Aprendizagem em Labirinto/fisiologia , Estado Pré-Diabético/sangue , Células Piramidais/citologia , Ratos Wistar
19.
J Comput Neurosci ; 45(3): 223-234, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30547292

RESUMO

Many neurons possess dendrites enriched with sodium channels and are capable of generating action potentials. However, the role of dendritic sodium spikes remain unclear. Here, we study computational models of neurons to investigate the functional effects of dendritic spikes. In agreement with previous studies, we found that point neurons or neurons with passive dendrites increase their somatic firing rate in response to the correlation of synaptic bombardment for a wide range of input conditions, i.e. input firing rates, synaptic conductances, or refractory periods. However, neurons with active dendrites show the opposite behavior: for a wide range of conditions the firing rate decreases as a function of correlation. We found this property in three types of models of dendritic excitability: a Hodgkin-Huxley model of dendritic spikes, a model with integrate and fire dendrites, and a discrete-state dendritic model. We conclude that fast dendritic spikes confer much broader computational properties to neurons, sometimes opposite to that of point neurons.


Assuntos
Potenciais de Ação/fisiologia , Modelos Neurológicos , Neurônios/fisiologia , Canais de Sódio/metabolismo , Sinapses/fisiologia , Animais , Biofísica , Dendritos/fisiologia , Neurônios/efeitos dos fármacos , Receptores de AMPA/metabolismo , Receptores de GABA/metabolismo
20.
Elife ; 72018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30575520

RESUMO

The piriform cortex (PCx) receives direct input from the olfactory bulb (OB) and is the brain's main station for odor recognition and memory. The transformation of the odor code from OB to PCx is profound: mitral and tufted cells in olfactory glomeruli respond to individual odorant molecules, whereas pyramidal neurons (PNs) in the PCx responds to multiple, apparently random combinations of activated glomeruli. How these 'discontinuous' receptive fields are formed from OB inputs remains unknown. Counter to the prevailing view that olfactory PNs sum their inputs passively, we show for the first time that NMDA spikes within individual dendrites can both amplify OB inputs and impose combination selectivity upon them, while their ability to compartmentalize voltage signals allows different dendrites to represent different odorant combinations. Thus, the 2-layer integrative behavior of olfactory PN dendrites provides a parsimonious account for the nonlinear remapping of the odor code from bulb to cortex.


Assuntos
Potenciais de Ação/efeitos dos fármacos , N-Metilaspartato/farmacologia , Córtex Piriforme/fisiologia , Animais , Cálcio/metabolismo , Dendritos/efeitos dos fármacos , Dendritos/fisiologia , Feminino , Ácido Glutâmico/metabolismo , Masculino , Modelos Neurológicos , Dinâmica não Linear , Condutos Olfatórios/efeitos dos fármacos , Condutos Olfatórios/fisiologia , Células Piramidais/efeitos dos fármacos , Células Piramidais/fisiologia , Ratos Wistar , Sinapses/efeitos dos fármacos , Sinapses/fisiologia
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