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Potential Generation (potential + generation)

Distribution by Scientific Domains
Life Sciences87%

Kinds of Potential Generation

  • action potential generation
    		•

    Selected Abstracts

    Roles of glutamate and GABA receptors in setting the developmental timing of spontaneous synchronized activity in the developing mouse cortex

    DEVELOPMENTAL NEUROBIOLOGY, Issue 12 2007
    Annette K. McCabe
    Abstract Spontaneous, synchronized electrical activity (SSA) plays important roles in nervous system development, but it is not clear what causes it to start and stop at the appropriate times. In previous work, we showed that when SSA in neonatal mouse cortex is blocked by TTX in cultured slices during its normal time of occurrence (E17,P3), it fails to stop at P3 as it does in control cultured slices, but instead persists through at least P10. This indicates that SSA is self-extinguishing. Here we use whole-cell recordings and [Ca2+]i imaging to compare control and TTX-treated slices to isolate the factors that normally extinguish SSA on schedule. In TTX-treated slices, SSA bursts average 4 s in duration, and have two components. The first, lasting about 1 s, is mediated by AMPA receptors; the second, which extends the burst to 4 s and is responsible for most of the action potential generation during the burst, is mediated by NMDA receptors. In later stage (P5,P9) control slices, after SSA has declined to about 4% of its peak frequency, bursts lack this long NMDA component. Blocking this NMDA component in P5,P9 TTX-treated slices reduces SSA frequency, but not to the low values found in control slices, implying that additional factors help extinguish SSA. GABAA inhibitors restore SSA in control slices, indicating that the emergence of GABAA -mediated inhibition is another major factor that helps terminate SSA. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007 [source]

    Metabotropic glutamate receptor 1 activity generates persistent, N -methyl- d -aspartate receptor-dependent depression of hippocampal pyramidal cell excitability

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2009
    J. P. Clement
    Abstract Metabotropic glutamate receptors (mGluRs) are involved in many forms of neuronal plasticity. In the hippocampus, they have well-defined roles in long-lasting forms of both synaptic and intrinsic plasticity. Here, we describe a novel form of long-lasting intrinsic plasticity that we call (S)-3,5-dihydroxyphenylglycine (DHPG)-mediated long-term depression of excitability (DHPG-LDE), and which is generated following transient pharmacological activation of group I mGluRs. In extracellular recordings from hippocampal slices, DHPG-LDE was expressed as a long-lasting depression of antidromic compound action potentials (cAPs) in CA1 or CA3 cells following a 4-min exposure to the group I mGluR agonist (S)-DHPG. A similar phenomenon was also seen for orthodromic fibre volleys evoked in CA3 axons. In single-cell recordings from CA1 pyramids, DHPG-LDE was manifest as persistent failures in antidromic action potential generation. DHPG-LDE was blocked by (S)-(+)- a -amino-4-carboxy-2-methylbenzeneacetic acid (LY367385), an antagonist of mGluR1, but not 2-methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP), an mGluR5 inhibitor. Although insensitive to antagonists of ,-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate/kainate and ,-aminobutyric acidA receptors, DHPG-LDE was blocked by antagonists of N -methyl- d -aspartate (NMDA) receptors. Similarly, in single-cell recordings, DHPG-mediated antidromic spike failures were eliminated by NMDA receptor antagonism. Long after (S)-DHPG washout, DHPG-LDE was reversed by mGluR1 antagonism. A 4-min application of (S)-DHPG also produced an NMDA receptor-dependent persistent depolarization of CA1 pyramidal cells. This depolarization was not solely responsible for DHPG-LDE, because a similar level of depolarization elicited by raising extracellular K+ increased the amplitude of the cAP. DHPG-LDE did not involve HCN channels or protein synthesis, but was eliminated by blockers of protein kinase C or tyrosine phosphatases. [source]

    AMPA and metabotropic glutamate receptors cooperatively generate inspiratory-like depolarization in mouse respiratory neurons in vitro

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2008
    Ryland W. Pace
    Abstract Excitatory transmission mediated by AMPA receptors is critical for respiratory rhythm generation. However, the role of AMPA receptors has not been fully explored. Here we tested the functional role of AMPA receptors in inspiratory neurons of the neonatal mouse preBötzinger complex (preBötC) using an in vitro slice model that retains active respiratory function. Immediately before and during inspiration, preBötC neurons displayed envelopes of depolarization, dubbed inspiratory drive potentials, that required AMPA receptors but largely depended on the Ca2+ -activated non-specific cation current (ICAN). We showed that AMPA receptor-mediated depolarization opened voltage-gated Ca2+ channels to directly evoke ICAN. Inositol 1,4,5-trisphosphate receptor-mediated intracellular Ca2+ release also evoked ICAN. Inositol 1,4,5-trisphosphate receptors acted downstream of group I metabotropic glutamate receptor activity but, here too, AMPA receptor-mediated Ca2+ influx was essential to trigger the metabotropic glutamate receptor contribution to inspiratory drive potential generation. This study helps to elucidate the role of excitatory transmission in respiratory rhythm generation in vitro. AMPA receptors in preBötC neurons initiate convergent signaling pathways that evoke post-synaptic ICAN, which underlies inspiratory drive potentials. The coupling of AMPA receptors with ICAN suggests that latent burst-generating intrinsic conductances are recruited by excitatory synaptic interactions among preBötC neurons in the context of respiratory network activity in vitro, exemplifying a rhythmogenic mechanism based on emergent properties of the network. [source]

    Disparate cholinergic currents in rat principal trigeminal sensory nucleus neurons mediated by M1 and M2 receptors: a possible mechanism for selective gating of afferent sensory neurotransmission

    EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2006
    Kristi A. Kohlmeier
    Abstract Neurons situated in the principal sensory trigeminal nucleus (PSTN) convey orofacial sensory inputs to thalamic relay regions and higher brain centres, and the excitability of these ascending tract cells is modulated across sleep/wakefulness states and during pain conditions. Moreover, acetylcholine release changes profoundly across sleep/wakefulness states and ascending sensory neurotransmission is altered by cholinergic agonists. An intriguing possibility is, therefore, that cholinergic mechanisms mediate such state-dependent modulation of PSTN tract neurons. We tested the hypotheses that cholinergic agonists can modulate PSTN cell excitability and that such effects are mediated by muscarinic receptor subtypes, using patch-clamp methods in rat and mouse. In all examined cells, carbachol elicited an electrophysiological response that was independent of action potential generation as it persisted in the presence of tetrodotoxin. Responses were of three types: depolarization, hyperpolarization or a biphasic response consisting of hyperpolarization followed by depolarization. In voltage-clamp mode, carbachol evoked corresponding inward, outward or biphasic currents. Moreover, immunostaining for the vesicle-associated choline transporter showed cholinergic innervation of the PSTN. Using muscarinic receptor antagonists, we found that carbachol-elicited PSTN neuron hyperpolarization was mediated by M2 receptors and depolarization, in large part, by M1 receptors. These data suggest that acetylcholine acting on M1 and M2 receptors may contribute to selective excitability enhancement or depression in individual, rostrally projecting sensory neurons. Such selective gating effects via cholinergic input may play a functional role in modulation of ascending sensory transmission, including across behavioral states typified by distinct cholinergic tone, e.g. sleep/wakefulness arousal levels or neuropathic pain conditions. [source]

    Expression of Nav1.6 sodium channels by Schwann cells at neuromuscular junctions: Role in the motor endplate disease phenotype

    GLIA, Issue 1 2006
    Magali Musarella
    Abstract In addition to their role in action potential generation and fast synaptic transmission in neurons, voltage-dependent sodium channels can also be active in glia. Terminal Schwann cells (TSCs) wrap around the nerve terminal arborization at the neuromuscular junction, which they contribute to shape during development and in the postdenervation processes. Using fluorescent in situ hybridization (FISH), immunofluorescence, and confocal microscopy, we detected the neuronal Nav1.6 sodium channel transcripts and proteins in TSCs in normal adult rats and mice. Nav1.6 protein co-localized with the Schwann cell marker S-100 but was not detected in the SV2-positive nerve terminals. The med phenotype in mice is due to a mutation in the SCN8A gene resulting in loss of Nav1.6 expression. It leads to early onset in postnatal life of defects in neuromuscular transmission with minimal alteration of axonal conduction. Strikingly, in mutant mice, the nonmyelinated pre-terminal region of axons showed abundant sprouting at neuromuscular junctions, and most of the ,-bungarotoxin-labeled endplates were devoid of S-100- or GFAP-positive TSCs. Using specific antibodies against the Nav1.2 and Nav1.6 sodium channels, ankyrin G and Caspr 1, and a pan sodium channel antibody, we found that a similar proportion of ankyrin G-positive nodes of Ranvier express sodium channels in mutant and wild-type animals and that nodal expression of Nav1.2 persists in med mice. Our data supports the hypothesis that the lack of expression of Nav1.6 in Schwann cells at neuromuscular junctions might play a role in the med phenotype. © 2005 Wiley-Liss, Inc. © 2005 Wiley-Liss, Inc. [source]

    Kinetic and functional analysis of transient, persistent and resurgent sodium currents in rat cerebellar granule cells in situ: an electrophysiological and modelling study

    THE JOURNAL OF PHYSIOLOGY, Issue 1 2006
    Jacopo Magistretti
    Cerebellar neurones show complex and differentiated mechanisms of action potential generation that have been proposed to depend on peculiar properties of their voltage-dependent Na+ currents. In this study we analysed voltage-dependent Na+ currents of rat cerebellar granule cells (GCs) by performing whole-cell, patch-clamp experiments in acute rat cerebellar slices. A transient Na+ current (INaT) was always present and had the properties of a typical fast-activating/inactivating Na+ current. In addition to INaT, robust persistent (INaP) and resurgent (INaR) Na+ currents were observed. INaP peaked at ,,40 mV, showed half-maximal activation at ,,55 mV, and its maximal amplitude was about 1.5% of that of INaT. INaR was elicited by repolarizing pulses applied following step depolarizations able to activate/inactivate INaT, and showed voltage- and time-dependent activation and voltage-dependent decay kinetics. The conductance underlying INaR showed a bell-shaped voltage dependence, with peak at ,35 mV. A significant correlation was found between GC INaR and INaT peak amplitudes; however, GCs expressing INaT of similar size showed marked variability in terms of INaR amplitude, and in a fraction of cells INaR was undetectable. INaT, INaP and INaR could be accounted for by a 13-state kinetic scheme comprising closed, open, inactivated and blocked states. Current-clamp experiments carried out to identify possible functional correlates of INaP and/or INaR revealed that in GCs single action potentials were followed by depolarizing afterpotentials (DAPs). In a majority of cells, DAPs showed properties consistent with INaR playing a role in their generation. Computer modelling showed that INaR promotes DAP generation and enhances high-frequency firing, whereas INaP boosts near-threshold firing activity. Our findings suggest that special properties of voltage-dependent Na+ currents provides GCs with mechanisms suitable for shaping activity patterns, with potentially important consequences for cerebellar information transfer and computation. [source]

    Regulation of glucagon release in mouse ,-cells by KATP channels and inactivation of TTX-sensitive Na+ channels

    THE JOURNAL OF PHYSIOLOGY, Issue 3 2000
    S. O. Göpel
    1The perforated patch whole-cell configuration of the patch-clamp technique was applied to superficial glucagon-secreting ,-cells in intact mouse pancreatic islets. 2,-cells were distinguished from the ,- and ,-cells by the presence of a large TTX-blockable Na+ current, a TEA-resistant transient K+ current sensitive to 4-AP (A-current) and the presence of two kinetically separable Ca2+ current components corresponding to low- (T-type) and high-threshold (L-type) Ca2+ channels. 3The T-type Ca2+, Na+ and A-currents were subject to steady-state voltage-dependent inactivation, which was half-maximal at ,45, ,47 and ,68 mV, respectively. 4Pancreatic ,-cells were equipped with tolbutamide-sensitive, ATP-regulated K+ (KATP) channels. Addition of tolbutamide (0·1 mm) evoked a brief period of electrical activity followed by a depolarisation to a plateau of ,30 mV with no regenerative electrical activity. 5Glucagon secretion in the absence of glucose was strongly inhibited by TTX, nifedipine and tolbutamide. When diazoxide was added in the presence of 10 mm glucose, concentrations up to 2 ,m stimulated glucagon secretion to the same extent as removal of glucose. 6We conclude that electrical activity and secretion in the ,-cells is dependent on the generation of Na+ -dependent action potentials. Glucagon secretion depends on low activity of KATP channels to keep the membrane potential sufficiently negative to prevent voltage-dependent inactivation of voltage-gated membrane currents. Glucose may inhibit glucagon release by depolarising the ,-cell with resultant inactivation of the ion channels participating in action potential generation. [source]

    EPISTEMOLOGICAL CONSIDERATIONS ON NEUROIMAGING , A CRUCIAL PREREQUISITE FOR NEUROETHICS

    BIOETHICS, Issue 6 2009
    CHRISTIAN G. HUBER
    ABSTRACT Purpose: Whereas ethical considerations on imaging techniques and interpretations of neuroimaging results flourish, there is not much work on their preconditions. In this paper, therefore, we discuss epistemological considerations on neuroimaging and their implications for neuroethics. Results: Neuroimaging uses indirect methods to generate data about surrogate parameters for mental processes, and there are many determinants influencing the results, including current hypotheses and the state of knowledge. This leads to an interdependence between hypotheses and data. Additionally, different levels of description are involved, especially when experiments are designed to answer questions pertaining to broad concepts like the self, empathy or moral intentions. Interdisciplinary theoretical frameworks are needed to integrate findings from the life sciences and the humanities and to translate between them. While these epistemological issues are not specific for neuroimaging, there are some reasons why they are of special importance in this context: Due to their inferential proximity, ,neuro-images' seem to be self-evident, suggesting directness of observation and objectivity. This has to be critically discussed to prevent overinterpretation. Additionally, there is a high level of attention to neuroimaging, leading to a high frequency of presentation of neuroimaging data and making the critical examination of their epistemological properties even more pressing. Conclusions: Epistemological considerations are an important prerequisite for neuroethics. The presentation and communication of the results of neuroimaging studies, the potential generation of new phenomena and new ,dysfunctions' through neuroimaging, and the influence on central concepts at the foundations of ethics will be important future topics for this discipline. [source]