In this paper we investigate the rate coding capabilities of neurons whose input signal are alterations of the base state of balanced inhibitory and excitatory synaptic currents. We consider different regimes of excitation-inhibition relationship and an established conductance-based leaky integrator model with adaptive threshold and parameter sets recreating biologically relevant spiking regimes. We find that given mean post-synaptic firing rate, counter-intuitively, increased ratio of inhibition to excitation generally leads to higher signal to noise ratio (SNR). On the other hand, the inhibitory input significantly reduces the dynamic coding range of the neuron. We quantify the joint effect of SNR and dynamic coding range by computing the metabolic efficiency-the maximal amount of information per one ATP molecule expended (in bits/ATP). Moreover, by calculating the metabolic efficiency we are able to predict the shapes of the post-synaptic firing rate histograms that may be tested on experimental data. Likewise, optimal stimulus input distributions are predicted, however, we show that the optimum can essentially be reached with a broad range of input distributions. Finally, we examine which parameters of the used neuronal model are the most important for the metabolically efficient information transfer.
- MeSH
- adenosintrifosfát metabolismus MeSH
- akční potenciály fyziologie MeSH
- excitační postsynaptické potenciály fyziologie MeSH
- membránové potenciály fyziologie MeSH
- modely neurologické * MeSH
- nervové vedení fyziologie MeSH
- nervový přenos fyziologie MeSH
- nervový útlum fyziologie MeSH
- neurony fyziologie MeSH
- počítačová simulace MeSH
- poměr signál - šum MeSH
- výpočetní biologie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Acute morphine exposure induces antinociceptive activity, but the underlying mechanisms in the central nervous system are unclear. Using whole-cell patch clamp recordings, we explore the role of morphine in the modulation of excitatory synaptic transmission in lateral amygdala neurons of rats. The results demonstrate that perfusion of 10 microM of morphine to the lateral amygdala inhibits the discharge frequency significantly. We further find that there are no significant influences of morphine on the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs). Interestingly, morphine shows no marked influence on the evoked excitatory postsynaptic currents (eEPSCs) in the lateral amygdala neurons. These results indicate that acute morphine treatment plays an important role in the modulation on the excitatory synaptic transmission in lateral amygdala neurons of rats.
- MeSH
- amygdala účinky léků fyziologie MeSH
- excitační postsynaptické potenciály účinky léků fyziologie MeSH
- krysa rodu rattus MeSH
- morfin farmakologie MeSH
- opioidní analgetika farmakologie MeSH
- orgánové kultury - kultivační techniky MeSH
- potkani Sprague-Dawley MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Endothelin-1 (ET-1) is a neuroactive protein produced in most brain cell types and participates in regulation of cerebral blood flow and blood pressure. In addition to its vascular effects, ET-1 affects synaptic and nonsynaptic neuronal and glial functions. Direct application of ET-1 to the hippocampus of immature rats results in cerebral ischemia, acute seizures, and epileptogenesis. Here, we investigated whether ET-1 itself modifies the excitability of hippocampal and cortical circuitry and whether acute seizures observed in vivo are due to nonvascular actions of ET-1. We used acute hippocampal and cortical slices that were preincubated with ET-1 (20 μM) for electrophysiological recordings. None of the slices preincubated with ET-1 exhibited spontaneous epileptic activity. The slope of the stimulus intensity-evoked response (input-output) curve and shape of the evoked response did not differ between ET-1-pretreated and control groups, suggesting no changes in excitability after ET-1 treatment. The threshold for eliciting an evoked response was not significantly increased in either hippocampal or cortical regions when pretreated with ET-1. Our data suggest that acute seizures after intrahippocampal application of ET-1 in rats are likely caused by ischemia rather than by a direct action of ET-1 on brain tissue.
- MeSH
- endotelin-1 farmakologie MeSH
- excitační postsynaptické potenciály fyziologie účinky léků MeSH
- hipokampus fyziologie účinky léků MeSH
- krysa rodu rattus MeSH
- nervový přenos fyziologie účinky léků MeSH
- potkani Wistar MeSH
- záchvaty chemicky indukované metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Glutamate AMPA receptors are critical for sensory transmission at the spinal cord dorsal horn (DH). Plasma membrane AMPA receptor endocytosis that can be induced by insulin may underlie long term modulation of synaptic transmission. Insulin receptors (IRs) are known to be expressed on spinal cord DH neurons, but their possible role in sensory transmission has not been studied. In this work the effect of insulin application on fast excitatory postsynaptic currents (EPSCs) mediated by AMPA receptors evoked in DH neurons was evaluated. Acute spinal cord slices from 6 to 10 day old mice were used to record EPSCs evoked in visually identified superficial DH neurons by dorsal root primary afferent stimulation. AMPA EPSCs could be evoked in all of the tested neurons. In 75% of the neurons the size of the AMPA EPSCs was reduced to 62.1% and to 68.9% of the control values when 0.5 or 10 microM insulin was applied. There was no significant change in the size of the AMPA EPSCs in the remaining 25% of DH neurons. The membrane permeable protein tyrosine kinase inhibitor, lavendustin A (10 microM), prevented the insulin induced AMPA EPSC depression. Our results suggest a possible role of the insulin pathway in modulation of sensory and nociceptive synaptic transmission in the spinal cord.
- MeSH
- AMPA receptory účinky léků metabolismus MeSH
- bolest metabolismus patofyziologie MeSH
- buňky zadních rohů míšních účinky léků metabolismus MeSH
- excitační postsynaptické potenciály účinky léků fyziologie MeSH
- fenoly farmakologie MeSH
- inhibitory enzymů farmakologie MeSH
- inzulin metabolismus farmakologie MeSH
- kyselina glutamová metabolismus MeSH
- metoda terčíkového zámku MeSH
- myši MeSH
- nervové receptory účinky léků metabolismus MeSH
- nervový přenos účinky léků fyziologie MeSH
- novorozená zvířata MeSH
- orgánové kultury - kultivační techniky MeSH
- receptor inzulinu účinky léků metabolismus MeSH
- signální transdukce účinky léků fyziologie MeSH
- tyrosinkinasy antagonisté a inhibitory metabolismus MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Modulation of synaptic transmission in the spinal cord dorsal horn is thought to be involved in the development and maintenance of different pathological pain states. The proinflamatory cytokine, tumor necrosis factor alpha (TNFalpha), is an established pain modulator in both the peripheral and the central nervous system. Up-regulation of TNFalpha and its receptors (TNFR) in dorsal root ganglion (DRG) cells and in the spinal cord has been shown to play an important role in neuropathic and inflammatory pain conditions. Transient receptor potential vanilloid 1 (TRPV1) receptors are known as molecular integrators of nociceptive stimuli in the periphery, but their role on the spinal endings of nociceptive DRG neurons is unclear. The endogenous TRPV1 receptor agonist N-oleoyldopamine (OLDA) was shown previously to activate spinal TRPV1 receptors. In our experiments the possible influence of TNFalpha on presynaptic spinal cord TRPV1 receptor function was investigated. Using the patch-clamp technique, miniature excitatory postsynaptic currents (mEPSCs) were recorded in superficial dorsal horn neurons in acute slices after incubation with 60 nM TNFalpha. A population of dorsal horn neurons with capsaicin sensitive primary afferent input recorded after the TNFalpha pretreatment had a basal mEPSC frequency of 1.35 +/- 0.20 Hz (n = 13), which was significantly higher when compared to a similar population of neurons in control slices (0.76 +/- 0.08 Hz; n = 53; P < 0.01). In control slices application of a low concentration of OLDA (0.2 uM) did not evoke any change in mEPSC frequency. After incubation with TNFalpha, OLDA (0.2 uM) application to slices induced a significant increase in mEPSC frequency (155.5 +/- 17.5%; P < 0.001; n = 10). Our results indicate that TNFalpha may have a significant impact on nociceptive signaling at the spinal cord level that could be mediated by increased responsiveness of presynaptic TRPV1 receptors to endogenous agonists. This could be of major importance, especially during pathological conditions, when increased levels of TNFalpha and TNFR are present in the spinal cord.
- MeSH
- analýza rozptylu MeSH
- buňky zadních rohů míšních účinky léků metabolismus MeSH
- dopamin analogy a deriváty farmakologie MeSH
- excitační postsynaptické potenciály účinky léků fyziologie MeSH
- kationtové kanály TRPV metabolismus MeSH
- krysa rodu rattus MeSH
- metoda terčíkového zámku MeSH
- mícha účinky léků metabolismus MeSH
- miniaturní postsynaptické potenciály účinky léků fyziologie MeSH
- nervový přenos účinky léků fyziologie MeSH
- potkani Wistar MeSH
- TNF-alfa farmakologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
N-methyl-d-aspartate (NMDA) receptors (NMDARs) are highly expressed in the CNS and mediate the slow component of excitatory transmission. The present study was aimed at characterizing the temperature dependence of the kinetic properties of native NMDARs, with special emphasis on the deactivation of synaptic NMDARs. We used patch-clamp recordings to study synaptic NMDARs at layer II/III pyramidal neurons of the rat cortex, recombinant GluN1/GluN2B receptors expressed in human embryonic kidney (HEK293) cells, and NMDARs in cultured hippocampal neurons. We found that time constants characterizing the deactivation of NMDAR-mediated excitatory postsynaptic currents (EPSCs) were similar to those of the deactivation of responses to a brief application of glutamate recorded under conditions of low NMDAR desensitization (whole-cell recording from cultured hippocampal neurons). In contrast, the deactivation of NMDAR-mediated responses exhibiting a high degree of desensitization (outside-out recording) was substantially faster than that of synaptic NMDA receptors. The time constants characterizing the deactivation of synaptic NMDARs and native NMDARs activated by exogenous glutamate application were only weakly temperature sensitive (Q(10)=1.7-2.2), in contrast to those of recombinant GluN1/GluN2B receptors, which are highly temperature sensitive (Q(10)=2.7-3.7). Ifenprodil reduced the amplitude of NMDAR-mediated EPSCs by approximately 50% but had no effect on the time course of deactivation. Analysis of GluN1/GluN2B responses indicated that the double exponential time course of deactivation reflects mainly agonist dissociation and receptor desensitization. We conclude that the temperature dependences of native and recombinant NMDAR are different; in addition, we contribute to a better understanding of the molecular mechanism that controls the time course of NMDAR-mediated EPSCs. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
- MeSH
- antagonisté excitačních aminokyselin farmakologie MeSH
- buněčné linie MeSH
- excitační postsynaptické potenciály fyziologie účinky léků MeSH
- hipokampus fyziologie účinky léků MeSH
- kinetika MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- kyselina glutamová metabolismus MeSH
- lidé MeSH
- mozková kůra fyziologie účinky léků MeSH
- nervový přenos fyziologie účinky léků MeSH
- piperidiny farmakologie MeSH
- potkani Wistar MeSH
- pyramidové buňky fyziologie účinky léků MeSH
- receptory N-methyl-D-aspartátu metabolismus MeSH
- synapse fyziologie účinky léků MeSH
- teplota MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- techniky in vitro MeSH
Lidská mysl a lidské vědomí jsou jedna funkce mozku jako celku, ačkoli některé oblasti mozku mohou hrát důležitější roli než jiné. Existující kvantové teorie nejsou schopné vysvětlit všechny aspekty lidské mysli a vědomí. Naše teorie je založena na volných elektronech, které se uvolňují během elektrofyziologických změn, jako jsou např. postsynaptické potenciály, depolarizace a hyperpolarizace neuronové membrány a akčních potenciálů pohybujících se podél axonů. Kvantové systémy formují kvantové elektronové pole, ve kterém jsou elektrony schopny spolu komunikovat prostřednictvím Pauliho síly. Tento způsob spojení může být nosičem subjektivního vědomí, které integruje a unifikuje funkce různých částí mozku. Daná vstupní veličina produkující obsah vědomí pochází z aktivity neuronů v různých částech mozkové kůry a dalších oblastech mozku.
Human mind and consciousness are a function of the whole brain as a whole, although some brain areas may play a more important role than the others. The existing quantum theories are unable to explain all the aspects of the mind and consciousness. Our theory is based on free electrons released during the electrophysiological changes such as postsynaptic potentials, depolarization and hyperpolarization of the neuronal membrane and action potentials moving along the axons. The quantum systems form a quantum electron field in which the electrons are able to communicate one with another by means of the Pauli force. This communication force may be a carrier of the subjective consciousness which integrates and unifies functions of various parts of the brain. The input producing the content of consciousness comes from the neuronal activity in various parts of the cerebral cortex and other brain areas.
- MeSH
- axony fyziologie MeSH
- duševní procesy fyziologie MeSH
- elektrické synapse fyziologie MeSH
- elektrofyziologie metody trendy MeSH
- elektrony MeSH
- excitační postsynaptické potenciály fyziologie MeSH
- kvantová teorie MeSH
- lidé MeSH
- mozek fyziologie MeSH
- nervový přenos fyziologie MeSH
- nervový systém - fyziologické jevy fyziologie MeSH
- psychofyziologie metody trendy MeSH
- teoretické modely MeSH
- vědomí fyziologie MeSH
- Check Tag
- lidé MeSH
It has been suggested that in mammals, trigeminal lamina I neurons play a role in the processing and transmission of sensory information from the orofacial region. We investigated the physiological and morphological properties of trigeminal subnucleus caudalis (Sp5C) lamina I neurons in slices prepared from the medulla oblongata of 13- to 15-day-old postnatal rats using patch-clamp recordings and subsequent biocytin-streptavidin-Alexa labeling. Twenty-five neurons were recorded and immunohistochemically stained. The Sp5C lamina I consisted of several types of neurons which, on the basis of their responses to somatic current injection, can be classified into four groups: tonic neurons, which fired throughout the depolarizing pulse; phasic neurons, which expressed an initial burst of action potentials; delayed onset neurons, which showed a significant delay of the first action potential; and single spike neurons, characterized by only one to five action potentials at the very beginning of the depolarizing pulse even at high levels of stimulation intensity. Electrical stimulation of the spinal trigeminal tract evoked AMPA receptor-mediated excitatory postsynaptic currents (EPSC) exhibiting a strong polysynaptic component. AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSC) were characterized by a 10-90% rise time of 0.50+/-0.06 ms and a decay time constant of 2.5+/-0.5 ms. The kinetic properties of NMDA receptor-mediated EPSCs were measured at +40 mV. The 10-90% rise time was 8+/-2 ms and the deactivation time constants were 94+/-31 and 339+/-72 ms, respectively. Intracellular staining and morphological analysis revealed three groups of neurons: fusiform, pyramidal, and multipolar. Statistical analysis indicated that the electrophysiological properties and morphological characteristics are correlated. Tonic and phasic neurons were fusiform or pyramidal and delayed onset and single spike neurons were multipolar. Our results show that both the physiological and morphological properties of Sp5C lamina I neurons exhibit significant differences, indicating their specific integration in the processing and transmission of sensory information from the orofacial region.
- MeSH
- algoritmy MeSH
- AMPA receptory fyziologie MeSH
- elektrofyziologie MeSH
- excitační postsynaptické potenciály fyziologie MeSH
- financování organizované MeSH
- imunohistochemie MeSH
- interpretace statistických dat MeSH
- krysa rodu rattus MeSH
- membránové potenciály fyziologie MeSH
- metoda terčíkového zámku MeSH
- nuclei trigemini anatomie a histologie fyziologie MeSH
- polarita buněk fyziologie MeSH
- potkani Wistar MeSH
- pyramidové buňky fyziologie MeSH
- receptory N-methyl-D-aspartátu fyziologie MeSH
- synapse fyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH