Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.186
Filtrar
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(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
3.
Science ; 364(6442)2019 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-31123108

RESUMO

Hippocampal pyramidal cells encode memory engrams, which guide adaptive behavior. Selection of engram-forming cells is regulated by somatostatin-positive dendrite-targeting interneurons, which inhibit pyramidal cells that are not required for memory formation. Here, we found that γ-aminobutyric acid (GABA)-releasing neurons of the mouse nucleus incertus (NI) selectively inhibit somatostatin-positive interneurons in the hippocampus, both monosynaptically and indirectly through the inhibition of their subcortical excitatory inputs. We demonstrated that NI GABAergic neurons receive monosynaptic inputs from brain areas processing important environmental information, and their hippocampal projections are strongly activated by salient environmental inputs in vivo. Optogenetic manipulations of NI GABAergic neurons can shift hippocampal network state and bidirectionally modify the strength of contextual fear memory formation. Our results indicate that brainstem NI GABAergic cells are essential for controlling contextual memories.


Assuntos
Aprendizagem por Associação/fisiologia , Neurônios GABAérgicos/fisiologia , Núcleos da Rafe/fisiologia , Animais , Feminino , Interneurônios/química , Interneurônios/fisiologia , Masculino , Testes de Memória e Aprendizagem , Camundongos , Camundongos Endogâmicos C57BL , Inibição Neural/fisiologia , Células Piramidais/química , Células Piramidais/fisiologia , Somatostatina/análise , Somatostatina/fisiologia , Ritmo Teta
4.
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
5.
PLoS Comput Biol ; 15(4): e1006932, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31009459

RESUMO

Pattern separation is a central concept in current theories of episodic memory: this computation is thought to support our ability to avoid confusion between similar memories by transforming similar cortical input patterns of neural activity into dissimilar output patterns before their long-term storage in the hippocampus. Because there are many ways one can define patterns of neuronal activity and the similarity between them, pattern separation could in theory be achieved through multiple coding strategies. Using our recently developed assay that evaluates pattern separation in isolated tissue by controlling and recording the input and output spike trains of single hippocampal neurons, we explored neural codes through which pattern separation is performed by systematic testing of different similarity metrics and various time resolutions. We discovered that granule cells, the projection neurons of the dentate gyrus, can exhibit both pattern separation and its opposite computation, pattern convergence, depending on the neural code considered and the statistical structure of the input patterns. Pattern separation is favored when inputs are highly similar, and is achieved through spike time reorganization at short time scales (< 100 ms) as well as through variations in firing rate and burstiness at longer time scales. These multiplexed forms of pattern separation are network phenomena, notably controlled by GABAergic inhibition, that involve many celltypes with input-output transformations that participate in pattern separation to different extents and with complementary neural codes: a rate code for dentate fast-spiking interneurons, a burstiness code for hilar mossy cells and a synchrony code at long time scales for CA3 pyramidal cells. Therefore, the isolated hippocampal circuit itself is capable of performing temporal pattern separation using multiplexed coding strategies that might be essential to optimally disambiguate multimodal mnemonic representations.


Assuntos
Hipocampo/fisiologia , Memória Episódica , Modelos Neurológicos , Potenciais de Ação/fisiologia , Animais , Biologia Computacional , Giro Denteado/fisiologia , Hipocampo/citologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/fisiologia , Células Piramidais/fisiologia
6.
Neural Netw ; 116: 119-138, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029053

RESUMO

The hippocampal theta rhythm (4-12 Hz) is one of the most important electrophysiological processes in the hippocampus, it participates in cognitive hippocampal functions, such as navigation in space, novelty detection, and declarative memory. We use neural network modeling to study the mechanism of theta rhythm emergence in the CA1 microcircuitry. Our model of the CA1 field includes biophysical representation of major cell types related to the theta rhythm emergence: excitatory pyramidal cells and two types of inhibitory interneurons, PV+ basket cells and oriens lacunosum-moleculare (OLM) cells. The main inputs to the CA1 cells come from the entorhinal cortex via perforant pathway, the CA3 field via Schaffer collaterals, and the medial septum via fimbria-fornix. By computer simulations we investigated the influence of each input, intrinsic parameters of neurons, and connections between neurons on phase coupling between the theta rhythm and the firing of pyramidal, PV+ basket and OLM cells in the CA1. We found that the input from the CA3 field via Schaffercollaterals plays a major role in the formation of phase relations that have been observed in experiments in vivo. The direct input from the medial septum participates in the formation of proper phase relations, but it is not crucial for the production of the theta rhythm in CA1 neural populations.


Assuntos
Região CA1 Hipocampal/fisiologia , Redes Neurais (Computação) , Células Piramidais/fisiologia , Ritmo Teta/fisiologia , Animais , Região CA1 Hipocampal/citologia , Córtex Entorrinal/fisiologia , Hipocampo/citologia , Hipocampo/fisiologia , Interneurônios/fisiologia , Neurônios/fisiologia
7.
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
8.
J Appl Oral Sci ; 27: e20180182, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30970112

RESUMO

Previous studies suggested that mastication activity can affect learning and memory function. However, most were focused on mastication impaired models by providing long-term soft diet. The effects of chewing food with various hardness, especially during the growth period, remain unknown. OBJECTIVE: To analyze the difference of hippocampus function and morphology, as characterized by pyramidal cell count and BDNF expression in different mastication activities. MATERIALS AND METHODS: 28-day old, post-weaned, male-Wistar rats were randomly divided into three groups (n=7); the first (K0) was fed a standard diet using pellets as the control, the second (K1) was fed soft food and the third (K2) was fed hard food. After eight weeks, the rats were decapitated, their brains were removed and placed on histological plates made to count the pyramid cells and quantify BDNF expression in the hippocampus. Data collected were compared using one-way ANOVA. RESULTS: Results confirmed the pyramid cell count (K0=169.14±27.25; K1=130.14±29.32; K2=128.14±39.02) and BDNF expression (K0=85.27±19.78; K1=49.57±20.90; K2=36.86±28.97) of the K0 group to be significantly higher than that of K1 and K2 groups (p<0.05); no significant difference in the pyramidal cell count and BNDF expression was found between K1 and K2 groups (p>0.05). CONCLUSION: A standard diet leads to the optimum effect on hippocampus morphology. Food consistency must be appropriately suited to each development stage, in this case, hippocampus development in post-weaned period.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/análise , Alimentos , Hipocampo/fisiologia , Mastigação/fisiologia , Células Piramidais/fisiologia , Animais , Contagem de Células , Dureza/fisiologia , Masculino , Distribuição Aleatória , Ratos Wistar , Valores de Referência , Fatores de Tempo
9.
Int Immunopharmacol ; 70: 338-353, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30852289

RESUMO

Neuroinflammation plays a prominent role in the pathophysiology and progression of schizophrenia. Thus, suppression of neuroinflammation may retard the progression of the disease. This study was designed to investigate whether morin, a bioactive compound with antipsychotic-like activity could reduce biomarkers of neuroinflammation and neurodegeneration in lipopolysaccharide (LPS)- and ketamine (KET)-induced schizophrenic-like behavior in mice. Animals were treated once daily intraperitoneally with morin (100 mg/kg), haloperidol (1 mg/kg), risperidone (0.5 mg/kg), or saline (10 mL/kg) in combination with LPS (0.1 mg/kg) for 14 consecutive days. However, from days 8-14, overt schizophrenia-like episode was produced with i.p. injection of KET (20 mg/kg) once daily. Schizophrenic-like behaviors: positive (open-field test), negative (social-interaction and social-memory tests) and cognitive (Y-maze test) symptoms were assessed on day 14. Thereafter, the levels and expressions of biomarkers of neuroinflammation were estimated in the striatum (ST), prefrontal cortex (PFC) and hippocampus (HC) using spectrophotometry, ELISA and immunohistochemistry. The effects of morin on cortical pyramidal neurons were estimated using Golgi-impregnation staining technique. LPS in combination with KET significantly (p < 0.05) induced schizophrenia-like behaviors, which was attenuated by morin. Morin significantly (p < 0.05) decreased tumor necrosis factor-α, interleukine-6 levels and myeloperoxidase activity in the ST, PFC and HC of mice treated with LPS + KET. Moreover, morin reduced regional brain expressions of cyclooxygenase-2, inducible nitric oxide synthase and nuclear factor kappa-B, and also rescued loss of pyramidal neurons in the PFC. Taken together, these findings suggest that morin reduces schizophrenic-like symptoms induced by LPS + KET via mechanisms related to inhibition of the release of pro-inflammatory mediators and suppression of degeneration of cortical pyramidal neurons in mice.


Assuntos
Antioxidantes/uso terapêutico , Flavonoides/uso terapêutico , Células Piramidais/efeitos dos fármacos , Esquizofrenia/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Córtex Cerebelar/citologia , Modelos Animais de Doenças , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/metabolismo , Ketamina/metabolismo , Lipopolissacarídeos/metabolismo , Masculino , Camundongos , Inflamação Neurogênica , Peroxidase/metabolismo , Células Piramidais/fisiologia , Comportamento Social , Degenerações Espinocerebelares , Fator de Necrose Tumoral alfa/metabolismo
10.
Ecotoxicol Environ Saf ; 174: 58-65, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-30822668

RESUMO

Di(2-ethylhexyl) phthalate (DEHP), as one of the most broadly representative phthalic acid esters, is used as a plasticizer in Polyvinyl chloride production. The exact neurotoxicologically effects of DEHP to human have not been adequately researched. In order to investigate the effects and mechanisms of DEHP exposure on neural circuit, the spatial learning and memory of Sprague Dawley (SD) rats was measured, and the cellular mechanisms underlying synaptic plasticity, cellular excitability and ion channels were detected. Our data showed that the spatial learning and memory was changed by DEHP (100 and 300 mg) treatment. Meanwhile, the frequency of mini Excitatory Postsynaptic Current (mEPSC) from CA3 pyramidal cells were significantly decreased by DEHP exposure (0.1 and 0.3 M); the firing threshold, membrane potential threshold, number, amplitude and latency of Action Potentials (Aps) of CA1 pyramidal cells were altered with the application of DEHP (0.1 and 0.3 M); furthermore, DEHP, both in 0.1 and 0.3 M could inhibit the voltage-gated potassium channel of CA1 pyramidal cells. Our results indicated that DEHP could impair the spatial learning and memory, and this impairment might due to the DEHP-induced suppression of the neuronal excitability and synaptic plasticity by inhibiting the voltage-gated potassium channel, supporting the hypothesis that DEHP could cause the disruption of neural function.


Assuntos
Dietilexilftalato/toxicidade , Memória/efeitos dos fármacos , Plastificantes/toxicidade , Aprendizagem Espacial/efeitos dos fármacos , Animais , Canais de Potássio de Abertura Dependente da Tensão da Membrana/antagonistas & inibidores , Células Piramidais/efeitos dos fármacos , Células Piramidais/fisiologia , Ratos , Ratos Sprague-Dawley
11.
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
12.
Neurosci Bull ; 35(3): 497-506, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30790215

RESUMO

Neuroligins (NLs) are postsynaptic cell-adhesion proteins that play important roles in synapse formation and the excitatory-inhibitory balance. They have been associated with autism in both human genetic and animal model studies, and affect synaptic connections and synaptic plasticity in several brain regions. Yet current research mainly focuses on pyramidal neurons, while the function of NLs in interneurons remains to be understood. To explore the functional difference among NLs in the subtype-specific synapse formation of both pyramidal neurons and interneurons, we performed viral-mediated shRNA knockdown of NLs in cultured rat cortical neurons and examined the synapses in the two major types of neurons. Our results showed that in both types of neurons, NL1 and NL3 were involved in excitatory synapse formation, and NL2 in GABAergic synapse formation. Interestingly, NL1 affected GABAergic synapse formation more specifically than NL3, and NL2 affected excitatory synapse density preferentially in pyramidal neurons. In summary, our results demonstrated that different NLs play distinct roles in regulating the development and balance of excitatory and inhibitory synapses in pyramidal neurons and interneurons.


Assuntos
Moléculas de Adesão Celular Neuronais/fisiologia , Interneurônios/fisiologia , Proteínas de Membrana/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Células Piramidais/fisiologia , Sinapses/fisiologia , Animais , Células Cultivadas , Córtex Cerebral/embriologia , Córtex Cerebral/fisiologia , Neurônios GABAérgicos/fisiologia , Isoformas de Proteínas/fisiologia , Ratos Sprague-Dawley
13.
eNeuro ; 6(1)2019 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30783614

RESUMO

The biological mechanisms underlying complex forms of learning requiring the understanding of rules based on previous experience are not yet known. Previous studies have raised the intriguing possibility that improvement in complex learning tasks requires the long-term modulation of intrinsic neuronal excitability, induced by reducing the conductance of the slow calcium-dependent potassium current (sIAHP) simultaneously in most neurons in the relevant neuronal networks in several key brain areas. Such sIAHP reduction is expressed in attenuation of the postburst afterhyperpolarization (AHP) potential, and thus in enhanced repetitive action potential firing. Using complex olfactory discrimination (OD) learning as a model for complex learning, we show that brief activation of the GluK2 subtype glutamate receptor results in long-lasting enhancement of neuronal excitability in neurons from controls, but not from trained rats. Such an effect can be obtained by a brief tetanic synaptic stimulation or by direct application of kainate, both of which reduce the postburst AHP in pyramidal neurons. Induction of long-lasting enhancement of neuronal excitability is mediated via a metabotropic process that requires PKC and ERK activation. Intrinsic neuronal excitability cannot be modulated by synaptic activation in neurons from GluK2 knock-out mice. Accordingly, these mice are incapable of learning the complex OD task. Moreover, viral-induced overexpression of Gluk2 in piriform cortex pyramidal neurons results in remarkable enhancement of complex OD learning. Thus, signaling via kainate receptors has a central functional role in higher cognitive abilities.


Assuntos
Aprendizagem por Discriminação/fisiologia , Percepção Olfatória/fisiologia , Córtex Piriforme/fisiologia , Células Piramidais/fisiologia , Receptores de Ácido Caínico/metabolismo , Animais , Agonistas de Aminoácidos Excitatórios/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Ácido Caínico/farmacologia , Masculino , Aprendizagem em Labirinto/fisiologia , Potenciais da Membrana/efeitos dos fármacos , Potenciais da Membrana/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Córtex Piriforme/efeitos dos fármacos , Proteína Quinase C/metabolismo , Células Piramidais/efeitos dos fármacos , Ratos Sprague-Dawley , Receptores de Ácido Caínico/genética , Técnicas de Cultura de Tecidos
14.
Methods Mol Biol ; 1948: 23-33, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30771167

RESUMO

The measurement of synaptic vesicle recycling in live neurons transfected with vesicular glutamate transporter fused to pHluorin (vGLUT-pHluorin) allows us to study exocytosis and endocytosis in neurons. When neurons are transfected with this protein we can measure the rate of vesicles fusing and internalizing from the membrane using live total internal reflection fluorescence (TIRF) imaging. Here, we describe transfection, culturing, and imaging of wild-type and αßγ-synuclein knockout hippocampal neurons. This technique can be used to evaluate the effect of different phenotypes and treatments in the physiology of synaptic vesicle recycling in cultured neurons.


Assuntos
Endocitose , Exocitose , Neurônios/fisiologia , Animais , Biomarcadores , Células Cultivadas , Processamento de Imagem Assistida por Computador , Camundongos , Imagem Molecular , Células Piramidais/fisiologia , Vesículas Sinápticas/metabolismo
15.
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
16.
Neurosci Lett ; 698: 192-197, 2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30641111

RESUMO

While the expression of ß3-adrenergic receptors is firmly established in adipose, kidney and heart tissue, their expression and function in the brain remains unclear despite their potential role in depression and stress-related disorders. This study aimed to investigate the expression of ß3-adrenoreceptors and their involvement in the mechanism controlling the resting holding current in layer V medial prefrontal cortex (mPFC) pyramidal neurons in young rats. Applications of the selective ß3-adrenergic receptor agonists BRL 37344 and SR 58611 A evoked inward currents in the tested neurons. The inward currents evoked by BRL 37344 or noradrenaline (a nonselective physiological adrenergic receptor agonist) were prevented or decreased, respectively, by the selective ß3-receptor antagonist L-748,337. Western blot and fluorescence immunohistochemistry analyses revealed ß3-adrenergic receptor protein expression in the mPFC. Thus, based on the results obtained here, functional ß3-adrenergic receptors are expressed in layer V mPFC pyramidal neurons and their activation evokes inward currents.


Assuntos
Etanolaminas/farmacologia , Neurônios/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Células Piramidais/efeitos dos fármacos , Agonistas Adrenérgicos , Animais , Masculino , Norepinefrina/metabolismo , Córtex Pré-Frontal/metabolismo , Células Piramidais/fisiologia , Ratos Wistar , Receptores Adrenérgicos/metabolismo , Descanso/fisiologia
17.
Neurosci Lett ; 698: 217-223, 2019 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-30668961

RESUMO

Many neurological diseases are related to disturbances of somatostatin- (SOM-) expressing interneurons in the cingulate cortex. Therefore, their role within the circuitry of the cingulate cortex needs to be investigated. We describe here the physiological time course of SOM effects onto pyramidal cell excitability and action potential discharge pattern. Furthermore, we show that the GRK2 inhibitor Gallein had no effect on the reduced SOM-induced response following repetitive SOM applications.


Assuntos
Giro do Cíngulo/fisiologia , Interneurônios/fisiologia , Células Piramidais/fisiologia , Somatostatina/metabolismo , Potenciais de Ação/fisiologia , Animais , Neurônios GABAérgicos/fisiologia , Camundongos Transgênicos
18.
Neuron ; 101(3): 500-513.e5, 2019 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-30635232

RESUMO

The relationship between mesoscopic local field potentials (LFPs) and single-neuron firing in the multi-layered neocortex is poorly understood. Simultaneous recordings from all layers in the primary visual cortex (V1) of the behaving mouse revealed functionally defined layers in V1. The depth of maximum spike power and sink-source distributions of LFPs provided consistent laminar landmarks across animals. Coherence of gamma oscillations (30-100 Hz) and spike-LFP coupling identified six physiological layers and further sublayers. Firing rates, burstiness, and other electrophysiological features of neurons displayed unique layer and brain state dependence. Spike transmission strength from layer 2/3 cells to layer 5 pyramidal cells and interneurons was stronger during waking compared with non-REM sleep but stronger during non-REM sleep among deep-layer excitatory neurons. A subset of deep-layer neurons was active exclusively in the DOWN state of non-REM sleep. These results bridge mesoscopic LFPs and single-neuron interactions with laminar structure in V1.


Assuntos
Interneurônios/fisiologia , Células Piramidais/fisiologia , Córtex Visual/fisiologia , Potenciais de Ação , Ritmo alfa , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Sono REM , Córtex Visual/citologia
19.
Neuroscience ; 402: 1-10, 2019 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-30685541

RESUMO

The growth of many cities has generated an increase in the emission of environmental pollutants. Exposure to these pollutants has been associated with increased mortality worldwide. These pollutants, such as ozone, produce reactive oxygen species (ROS), which cause oxidative stress throughout the body. It has been observed that there is a relationship between chronic oxidative stress and the development of degenerative diseases typical of old age such as amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, and Huntington's disease. The purpose of this research was to evaluate whether chronic exposure to ozone produces a deleterious effect on density and morphology of dendritic spines in CA1 of dorsal hippocampus and on learning and memory of object-place recognition. Rats were exposed to ozone or to ozone-free air for a period of 15, 30, 60, or 90 days. The principal results indicate that chronic oxidative stress induced by ozone produces a decrease in the density of dendritic spines, a decrease in thin and mushroom spine ratios, and an increase in stubby spine ratio, as well as a deficit in learning and memory of the object-place recognition task. These results indicate that chronic ozone exposure produces a loss in the inputs of CA1 neurons of the dorsal hippocampus, which may be the source of the cognitive deficits observed in the object-place recognition task, as indicated by the decrease in density of dendritic spines; these alterations are similar to those reported in some neurodegenerative diseases such as Alzheimer's disease.


Assuntos
Região CA1 Hipocampal/efeitos dos fármacos , Espinhas Dendríticas/efeitos dos fármacos , Ozônio/administração & dosagem , Células Piramidais/efeitos dos fármacos , Recognição (Psicologia)/efeitos dos fármacos , Animais , Região CA1 Hipocampal/fisiologia , Espinhas Dendríticas/fisiologia , Masculino , Estresse Oxidativo , Células Piramidais/fisiologia , Ratos Wistar
20.
eNeuro ; 6(1)2019 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30693314

RESUMO

Memory of a recently eaten meal can serve as a powerful mechanism for controlling future eating behavior because it provides a record of intake that likely outlasts most physiological signals generated by the meal. In support, impairing the encoding of a meal in humans increases the amount ingested at the next eating episode. However, the brain regions that mediate the inhibitory effects of memory on future intake are unknown. In the present study, we tested the hypothesis that dorsal hippocampal (dHC) and ventral hippocampal (vHC) glutamatergic pyramidal neurons play a critical role in the inhibition of energy intake during the postprandial period by optogenetically inhibiting these neurons at specific times relative to a meal. Male Sprague Dawley rats were given viral vectors containing CaMKIIα-eArchT3.0-eYFP or CaMKIIα-GFP and fiber optic probes into dHC of one hemisphere and vHC of the other. Compared to intake on a day in which illumination was not given, inhibition of dHC or vHC glutamatergic neurons after the end of a chow, sucrose, or saccharin meal accelerated the onset of the next meal and increased the amount consumed during that next meal when the neurons were no longer inhibited. Inhibition given during a meal did not affect the amount consumed during that meal or the next one but did hasten meal initiation. These data show that dHC and vHC glutamatergic neuronal activity during the postprandial period is critical for limiting subsequent ingestion and suggest that these neurons inhibit future intake by consolidating the memory of the preceding meal.


Assuntos
Ingestão de Alimentos/fisiologia , Hipocampo/fisiologia , Período Pós-Prandial/fisiologia , Células Piramidais/fisiologia , Animais , Sacarose na Dieta , Comportamento Alimentar/fisiologia , Ácido Glutâmico/metabolismo , Memória/fisiologia , Inibição Neural , Optogenética , Ratos Sprague-Dawley , Sacarina , Técnicas de Cultura de Tecidos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA