RESUMO
Neurons in the medial superior olive (MSO) and lateral superior olive (LSO) of the auditory brainstem code for sound-source location in the horizontal plane, extracting interaural time differences (ITDs) from the stimulus fine structure and interaural level differences (ILDs) from the stimulus envelope. Here, we demonstrate a postsynaptic gradient in temporal processing properties across the presumed tonotopic axis; neurons in the MSO and the low-frequency limb of the LSO exhibit fast intrinsic electrical resonances and low input impedances, consistent with their processing of ITDs in the temporal fine structure. Neurons in the high-frequency limb of the LSO show low-pass electrical properties, indicating they are better suited to extracting information from the slower, modulated envelopes of sounds. Using a modeling approach, we assess ITD and ILD sensitivity of the neural filters to natural sounds, demonstrating that the transformation in temporal processing along the tonotopic axis contributes to efficient extraction of auditory spatial cues.
Assuntos
Vias Auditivas/fisiologia , Implantes Cocleares , Modelos Neurológicos , Núcleo Olivar/fisiologia , Localização de Som/fisiologia , Estimulação Acústica , Animais , Vias Auditivas/citologia , Sinais (Psicologia) , Cobaias , Percepção Sonora/fisiologia , Ruído , Núcleo Olivar/citologia , Técnicas de Patch-Clamp , Ratos , Percepção Espacial/fisiologiaRESUMO
Signal and noise correlations, a prominent feature of cortical activity, reflect the structure and function of networks during sensory processing. However, in addition to reflecting network properties, correlations are also shaped by intrinsic neuronal mechanisms. Here we show that spike threshold transforms correlations by creating nonlinear interactions between signal and noise inputs; even when input noise correlation is constant, spiking noise correlation varies with both the strength and correlation of signal inputs. We characterize these effects systematically in vitro in mice and demonstrate their impact on sensory processing in vivo in gerbils. We also find that the effects of nonlinear correlation transfer on cortical responses are stronger in the synchronized state than in the desynchronized state, and show that they can be reproduced and understood in a model with a simple threshold nonlinearity. Since these effects arise from an intrinsic neuronal property, they are likely to be present across sensory systems and, thus, our results are a critical step toward a general understanding of how correlated spiking relates to the structure and function of cortical networks.
Assuntos
Potenciais de Ação/fisiologia , Córtex Cerebral/fisiologia , Rede Nervosa/fisiologia , Ruído , Dinâmica não Linear , Estimulação Acústica/métodos , Animais , Gerbillinae , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
UNLABELLED: The aim of this study is to identify the criteria which would allow a differentiation between the Minnesota Multiphasic Personality Inventory-2 (MMPI-2) profiles, obtained from patients who present with problems of minimization of attitude (dissembling) who have shown a minimization of their problems; from patients who answered in a spontaneous and genuine fashion. METHODS: Six hundred and fifty five MMPI profiles of outpatients of the Clinical Psychology Unit, University Hospital, Sapienza University of Rome. Patients were subdivided into two groups, based on the reason for attending: those who submitted voluntarily to a psychodiagnostic assessment and those who were assessed by request of an outside authority, e.g., in the case of those whose driving license was suspended. It has hypothesized that the latter group would not present with problems which would preclude obtaining the benefits required. The variables analyzed were the clinical scale and the validity scale MMPI-2, index F-K and the Ds scale of Gough. On the basis of the values of the F-K index and Ds scale, the patients were reclassified into three simulation categories: spontaneous registration; defended and doubtful's. RESULTS: All indexes, validity scales and clinical scales of the standard profile were found to have significant differences between the "dissimulation" and "normal" groups. Sensibility and specificity of profile classification was according to both indexes 76%. CONCLUSIONS: Current evidence indicates that simulation of pathology is identifiable in MMPI-2 profiles. Our data demonstrate that it is possible to identify case of defensive minimization. These results confirm the hypothesis that simulation is a dimensional characteristic of MMPI which can reach extreme values in both ways: worsening of slight problems or suppression of existing problems.
Assuntos
MMPI , Simulação de Doença , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Simulação de Doença/diagnóstico , Pessoa de Meia-Idade , Adulto JovemRESUMO
The mouse mutant ducky and its allele ducky(2J) represent a model for absence epilepsy characterized by spike-wave seizures and cerebellar ataxia. These mice have mutations in Cacna2d2, which encodes the alpha2delta-2 calcium channel subunit. Of relevance to the ataxic phenotype, alpha2delta-2 mRNA is strongly expressed in cerebellar Purkinje cells (PCs). The Cacna2d2(du2J) mutation results in a 2 bp deletion in the coding region and a complete loss of alpha2delta-2 protein. Here we show that du(2J)/du(2J) mice have a 30% reduction in somatic calcium current and a marked fall in the spontaneous PC firing rate at 22 degrees C, accompanied by a decrease in firing regularity, which is not affected by blocking synaptic input to PCs. At 34 degrees C, du(2J)/du(2J) PCs show no spontaneous intrinsic activity. Du(2J)/du(2J) mice also have alterations in the cerebellar expression of several genes related to PC function. At postnatal day 21, there is an elevation of tyrosine hydroxylase mRNA and a reduction in tenascin-C gene expression. Although du(2J)/+ mice have a marked reduction in alpha2delta-2 protein, they show no fall in PC somatic calcium currents or increase in cerebellar tyrosine hydroxylase gene expression. However, du(2J)/+ PCs do exhibit a significant reduction in firing rate, correlating with the reduction in alpha2delta-2. A hypothesis for future study is that effects on gene expression occur as a result of a reduction in somatic calcium currents, whereas effects on PC firing occur as a long-term result of loss of alpha2delta-2 and/or a reduction in calcium currents and calcium-dependent processes in regions other than the soma.
Assuntos
Canais de Cálcio/genética , Regulação da Expressão Gênica/genética , Mutação , Células de Purkinje/metabolismo , Células de Purkinje/patologia , Animais , Células COS , Canais de Cálcio/fisiologia , Chlorocebus aethiops , Técnicas In Vitro , Camundongos , Camundongos Knockout , Camundongos TransgênicosRESUMO
BACKGROUND: Neural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to neurodegenerative disease. Overexpression of the myc family transcription factors in human primary cells from developing cortex and mesencephalon has produced two stable multipotential NSC lines (ReNcell VM and CX) that can be continuously expanded in monolayer culture. RESULTS: In the undifferentiated state, both ReNcell VM and CX are nestin positive and have resting membrane potentials of around -60 mV but do not display any voltage-activated conductances. As initially hypothesized, using standard methods (stdD) for differentiation, both cell lines can form neurons, astrocytes and oligodendrocytes according to immunohistological characteristics. However it became clear that this was not true for electrophysiological features which designate neurons, such as the firing of action potentials. We have thus developed a new differentiation protocol, designated 'pre-aggregation differentiation' (preD) which appears to favor development of electrophysiologically functional neurons and to lead to an increase in dopaminergic neurons in the ReNcell VM line. In contrast, the protocol used had little effect on the differentiation of ReNcell CX in which dopaminergic differentiation was not observed. Moreover, after a week of differentiation with the preD protocol, 100% of ReNcell VM featured TTX-sensitive Na+-channels and fired action potentials, compared to 25% after stdD. Currents via other voltage-gated channels did not appear to depend on the differentiation protocol. ReNcell CX did not display the same electrophysiological properties as the VM line, generating voltage-dependant K+ currents but no Na+ currents or action potentials under either stdD or preD differentiation. CONCLUSION: These data demonstrate that overexpression of myc in NSCs can be used to generate electrophysiologically active neurons in culture. Development of a functional neuronal phenotype may be dependent on parameters of isolation and differentiation of the cell lines, indicating that not all human NSCs are functionally equivalent.
Assuntos
Diferenciação Celular/fisiologia , Córtex Cerebral/citologia , Mesencéfalo/citologia , Neurônios/fisiologia , Células-Tronco/fisiologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta à Radiação , Estimulação Elétrica/métodos , Feto , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Potenciais da Membrana/fisiologia , Potenciais da Membrana/efeitos da radiação , Proteínas do Tecido Nervoso/metabolismo , Técnicas de Patch-Clamp/métodos , Células-Tronco/efeitos dos fármacos , Fatores de Tempo , Tubulina (Proteína)/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
Activation of metabotropic glutamate receptors by (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD) produced pre- and postsynaptic effects on hypoglossal motoneurons (HMs) patch clamped in thin slices from neonatal rat brainstem. t-ACPD depolarized HMs (with parallel increase in R(in)), induced membrane oscillations, and depressed glutamatergic transmission. However, t-ACPD neither changed the discharge pattern of HMs induced by current pulses nor modulated the spike afterhyperpolarization. The only apparent alteration in firing was the delayed onset of the second spike in a train. The present results provide new evidence that activation of metabotropic glutamate receptors could influence HM excitability by changing the cell responsiveness to synaptic inputs rather than via obvious alterations in the spike firing properties.
Assuntos
Potenciais Pós-Sinápticos Excitadores/fisiologia , Nervo Hipoglosso/fisiologia , Neurônios Motores/fisiologia , Receptores de Glutamato Metabotrópico/fisiologia , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Animais , Animais Recém-Nascidos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Nervo Hipoglosso/efeitos dos fármacos , Neurônios Motores/efeitos dos fármacos , Terminações Pré-Sinápticas/efeitos dos fármacos , Terminações Pré-Sinápticas/fisiologia , Ratos , Receptores de Glutamato Metabotrópico/agonistasRESUMO
Since constitutively-high intracellular Ca(2+) ([Ca(2+)](i)) may confer hypoglossal motoneurons special vulnerability to excitoxic damage, we investigated the spatiotemporal dynamics of [Ca(2+)](i) and its relation to spike firing of rat hypoglossal motoneurons recorded under whole-cell patch clamp coupled with high resolution [Ca(2+)](i) imaging. A rise in [Ca(2+)](i), appearing in conjunction with single action potentials and becoming larger during spike trains, was first detected immediately beneath the cell membrane area, peaked 10-20 ms after each spike, and propagated to the cell core with slow decay time. Depletion of ryanodine-sensitive [Ca(2+)](i) stores by caffeine increased background [Ca(2+)](i), augmented the spike medium afterhyperpolarization, slowed down the action potential firing rate and depolarized cells (after an early hyperpolarization). The decay time constant of [Ca(2+)](i) transients was more than doubled by caffeine, although peak [Ca(2+)](i) remained unchanged. It is suggested that the main role of caffeine-sensitive stores was to buffer [Ca(2+)](i) elevated by sustained firing and to control spike accommodation.
Assuntos
Cafeína/farmacologia , Cálcio/fisiologia , Nervo Hipoglosso/efeitos dos fármacos , Neurônios Motores/efeitos dos fármacos , Potenciais de Ação , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Corantes Fluorescentes , Nervo Hipoglosso/citologia , Nervo Hipoglosso/fisiologia , Técnicas In Vitro , Líquido Intracelular/metabolismo , Neurônios Motores/metabolismo , Neurônios Motores/fisiologia , Compostos Orgânicos , Técnicas de Patch-Clamp , RatosRESUMO
In many brain regions, Ca(2+) influx through presynaptic P2X receptors influences GABA release from interneurones. In patch-clamp recordings of Purkinje cells (PCs) in rat cerebellar slices, broad spectrum P2 receptor antagonists, PPADS (30microM) or suramin (12microM), result in a decreased amplitude and increased failure rate of minimal evoked GABAergic synaptic currents from basket cells. The effect is mimicked by desensitizing P2X1/3-containing receptors with alpha,beta-methylene ATP. This suggests presynaptic facilitation of GABA release via P2XR-mediated Ca(2+) influx activated by endogenously released ATP. In contrast, activation of P2Y4 receptors (using UTP, 30microM, but not P2Y1 or P2Y6 receptor ligands) results in inhibition of GABA release. Immunological studies reveal the presence of most known P2Rs in >or=20% of GABAergic terminals in the cerebellum. P2X3 receptors and P2Y4 receptors occur in approximately 60% and 50% of GABAergic synaptosomes respectively and are localized presynaptically. Previous studies report that PC output is also influenced by postsynaptic purinergic receptors located on both PCs and interneurones. The high Ca(2+) permeability of the P2X receptor and the ability of ATP to influence intracellular Ca(2+) levels via P2Y receptor-mediated intracellular pathways make ATP the ideal transmitter for the multisite bidirectional modulation of the cerebellar cortical neuronal network.
Assuntos
Sinalização do Cálcio , Cerebelo/metabolismo , Terminações Pré-Sinápticas/metabolismo , Células de Purkinje/metabolismo , Receptores Pré-Sinápticos/metabolismo , Receptores Purinérgicos P2/metabolismo , Ácido gama-Aminobutírico/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Sinalização do Cálcio/efeitos dos fármacos , Córtex Cerebelar/metabolismo , Cerebelo/citologia , Potenciais Evocados/efeitos dos fármacos , Técnicas In Vitro , Masculino , Potenciais da Membrana/efeitos dos fármacos , Modelos Biológicos , Terminações Pré-Sinápticas/efeitos dos fármacos , Agonistas do Receptor Purinérgico P2 , Antagonistas do Receptor Purinérgico P2 , Fosfato de Piridoxal/análogos & derivados , Fosfato de Piridoxal/farmacologia , Ratos , Ratos Wistar , Receptores de GABA-A/metabolismoRESUMO
The function of GABA or glycine during early postnatal development remains controversial as their action is reported as either excitatory or inhibitory. The present study addressed the question of the functional role of GABA or glycine on rat motoneurons shortly after birth. For this purpose, using in vitro preparations from immature rats (postnatal age, P0-P4 days), we recorded from lumbar spinal motoneurons and hypoglossal motoneurons. All data were obtained under current clamp conditions (recording with potassium methylsulphate containing electrodes) from cells at about -70 mV resting potential. On spinal motoneurons we used the glycinergic and GABAergic recurrent postsysnaptic potential (PSP) mediated by Renshaw cells to assess its impact on excitatory synaptic inputs from dorsal afferent fibres. Despite its depolarizing nature, the recurrent PSP consistently inhibited synaptic excitation of lumbar motoneurons. On hypoglossal motoneurons, exogenously applied GABA or glycine produced depolarization with decreased input resistance. This response was always associated with inhibition of cell firing induced by intracellular current pulses. Even when the membrane potential was repolarized to resting level in the presence of GABA or glycine, hypoglossal motoneurons failed to generate spikes. Conversely, similar depolarization produced by glutamate consistently facilitated spike firing. GABAergic and glycinergic synaptic potentials evoked by focal stimulation of the reticular formation inhibited firing and/or increased firing latency in the majority of hypoglossal motoneurons. These results indicate that, immediately after birth, rat motoneurons were inhibited by synaptically released or exogenously applied GABA or glycine.