- A résumé What needs to be done? Fill out the application and enclose the résumé Regardless of the length of life a ré... moreA résumé
What needs to be done?
Fill out the application
and enclose the résumé
Regardless of the length of life
a résumé is best kept short.
Concise, well-chosen facts, are de rigueur.
Landscapes are replaced by addresses,
shaky memories give way to unshakable dates.
Of all your loves, mention only the marriage;
of all your children, only those who were born.
Who knows you matters more than whom you know.
Trips only if taken abroad.
Memberships in what but without why.
Honors, but not how they were earned.
Write as if you'd never talked to yourself
and always kept yourself at arm's length.
Pass over in silence your dogs, cats, birds,
dusty keepsakes, friends, and dreams.
Price, not worth,
and title, not what's inside.
His shoe size, not where he's off to,
tat one you pass off as yourself.
In addition a photograph with one ear showing.
What matters is its shape, not what it hears.
What is there to hear, anyway?
The clatter of paper shredders.
Wislava Szimborska
The people on the bridge, 1986
Transl. S. Baranczak ans C. Cavanaghedit
Adipose‐derived mesenchymal stem cells (ASCs) may transdifferentiate into cells belonging to mesodermal, endodermal, and ectodermal lineages. The aim of this study was to verify whether a neural differentiation of ASCs could be induced by... more
Adipose‐derived mesenchymal stem cells (ASCs) may transdifferentiate into cells belonging to mesodermal, endodermal, and ectodermal lineages. The aim of this study was to verify whether a neural differentiation of ASCs could be induced by a conditioned medium (CM) obtained from cultures of olfactory ensheathing cells (OECs) or Schwann cells (SCs). ASCs were isolated from the stromal vascular fraction of adipose tissue and expanded for 2–3 passages. They were then cultured in OEC‐CM or SC‐CM for 24 hr or 7 days. At each stage, the cells were tested by immunocytochemistry and flow cytometer analysis to evaluate the expression of typical neural markers such as Nestin, PGP 9.5, MAP2, Synapsin I, and GFAP. Results show that both conditioned media induced similar positive effects, as all tested markers were overexpressed, especially at day 7. Overall, an evident trend toward neuronal or glial differentiation was not clearly detectable in many cases. Nevertheless, a higher tendency toward ...
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Research Interests: Chemistry, Kinetics, Medicine, Ion Channels, Pubmed, and 7 moreAnimals, Potassium, Neurons, Rats, Voltage Clamp, Electric Conductivity, and Clamp
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1. Adult and intact sympathetic neurones of isolated rat superior cervical ganglia were subjected to a two‐electrode voltage‐clamp analysis at 37 degrees C in order to investigate the Ca2(+)‐dependent K+ conductance. 2. At each potential... more
1. Adult and intact sympathetic neurones of isolated rat superior cervical ganglia were subjected to a two‐electrode voltage‐clamp analysis at 37 degrees C in order to investigate the Ca2(+)‐dependent K+ conductance. 2. At each potential a Ca2(+)‐dependent K+ current, IKCa, was determined as the difference between the current that could be attributed to the voltage‐dependent K+ current, IKV, following Ca2+ channel blockade by Cd2+ and the total current generated. The final IKCa curves were obtained after correcting the experimental tracings for the underlying ICa current component. 3. IKCa became detectable during commands to ‐30 mV. About 3.6 x 10(5) Ca2+ ions are required to enter the cell before IKCa is initiated. The current was modelled on the basis of a 0.4‐0.6 ms delay followed by an exponential activation of a fast component, IKCaf, simultaneously with a much slower exponential activation, IKCas. Experiments indicate a sigmoidal activation curve for the fast conductance, gKCf, with half‐maximal activation at ‐13.0 mV and a slope factor of 4.7 mV (for 5 mM‐Ca2+ in the bath). The associated time constant, tau kcf, ranged from 0.8 to 2.0 ms. The slow conductance exhibited a similar steady‐state activation curve but an activation time constant in the 48‐280 ms range. The maximum mean gKC was 0.32 microS per neurone for either the fast or slow component. 4. Excess K+ ions accumulate in the perineuronal space during K+ current flow giving rise to rapidly occurring, large K+ reversal potential (EK) modifications (up to ‐45 mV for the largest currents). The kinetics of K+ extracellular load can be described satisfactorily by a simple exponential function (tau = 0.9‐2.8 ms). The characteristics of K+ wash‐out appear similar to those of accumulation. 5. The immediate effect of such an extracellular K+ build‐up is to make the apparent IKCa activation kinetics faster and to reduce (up to 50%) the true value of the K+ conductance. We simulated the predictions of a K+ diffusion model and generated new functions describing the IKCa steady‐state activation, activation rate and maximum conductance values which satisfactorily reconstruct the IKCa current tracings together with the K+ accumulation process near the membrane. 6. A small component of the Ca2(+)‐dependent K+ current, IAHP, was observed which survived at membrane potential levels negative to ‐40 mV. Increasing Ca2+ influx by applying longer pulses enhanced IAHP, which on the other hand was also activated by depolarizations of short duration.(ABSTRACT TRUNCATED AT 400 WORDS)
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Research Interests: Physiology, Chemistry, Kinetics, Medicine, Ion Channels, and 15 moreBiological Sciences, Animals, Potassium, Conductance, Neurons, Cadmium, Constant Time Delay, Rats, Sodium, Tetraethylammonium, Membrane Potential, Action Potentials, Depolarization, Medical and Health Sciences, and In Vitro Techniques
Fresh ideas suggested by the first numerical reconstruction of the action potential in a mammalian neuron are 1) role of the A-current and the starting membrane potential level, 2) fast kinetics of the pericellular K+ accumulation, and 3)... more
Fresh ideas suggested by the first numerical reconstruction of the action potential in a mammalian neuron are 1) role of the A-current and the starting membrane potential level, 2) fast kinetics of the pericellular K+ accumulation, and 3) spike-related Ca2+ movements.
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1. The calcium currents evoked by membrane depolarization in the mature and intact rat sympathetic neurone have been studied at 37 degrees C using two‐electrode voltage‐clamp analysis. 2. Under conditions that eliminate Na+ and K+... more
1. The calcium currents evoked by membrane depolarization in the mature and intact rat sympathetic neurone have been studied at 37 degrees C using two‐electrode voltage‐clamp analysis. 2. Under conditions that eliminate Na+ and K+ currents and 5 mM‐external Ca2+, inward currents were observed that activated at about ‐30 mV and reached maximum amplitude between 0 and +10 mV with time‐to‐peak values (2.7‐1.9 ms) decreasing with increasing membrane depolarization. Thereafter, calcium current (ICa) decayed to a virtually zero level with maintained depolarization. Two exponentials were required to describe the total inactivation process. The faster rate (tau = 29.3‐17.6 ms) is ten times the slower rate and proved to be only slightly voltage‐dependent. Double‐pulse experiments gave a similar time course of turn‐off. 3. No steady‐state inactivation was removed at holding potentials between ‐40 and ‐70 mV and indirect data suggest that all the ICa was available at ‐50 mV. Within the ‐30 to ...
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Research Interests: Physiology, Biophysics, Chemistry, Calcium, Medicine, and 15 moreIon Channels, Biological Sciences, Female, Animals, Potassium, Conductance, Neurons, Rats, Tetraethylammonium, Aminopyridine, Membrane Potential, Action Potentials, Electric Conductivity, Medical and Health Sciences, and In Vitro Techniques
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Research Interests: Physiology, Chemistry, Kinetics, Medicine, Ion Channels, and 15 moreBiological Sciences, Animals, Temperature, Conductance, Neurons, Constant Time Delay, Rats, Sodium, Time Factors, Tetrodotoxin, Tetraethylammonium, Membrane Potential, Action Potentials, Medical and Health Sciences, and In Vitro Techniques
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Publisher Summary This chapter describes the influence of prostaglandins (PGs) of E type on synaptic transmission of the guinea-pig superior cervical ganglion. The chapter discusses a study to test the hypothesis that PGEs are involved in... more
Publisher Summary This chapter describes the influence of prostaglandins (PGs) of E type on synaptic transmission of the guinea-pig superior cervical ganglion. The chapter discusses a study to test the hypothesis that PGEs are involved in pre-synaptic control of acetylcholine release. The addition of PGE1 10−7–10−8 M to the superfusing medium significantly reduced the efficacy of synaptic transmission in guinea-pig isolated superior cervical ganglion. It is found that when single ganglion neurons were impaled under PGEs treatment, action potentials evoked by liminar orthodromic stimulation disappeared within 2–3 min and were substituted in the tracings by excitatory postsynaptic potentials (EPSPs) of progressively decreasing amplitude. A neuron in which synaptic input was reduced to a single active fiber is examined. In these conditions, electrical orthodromic stimulation gave rise only to long series of evoked EPSPs of fluctuating amplitude. The lower tracing was taken after PGE1 had been added to the superfusing medium. It can be seen that the number of failures in the tracing is clearly increased and the amplitude of the elementary event doesn't appear to be significantly changed. The effect of PGEs on ganglionic synaptic transmission can be even better appreciated in which the distribution of evoked EPSPs amplitude obtained before and after PGE treatment of ganglion preparations is shown.
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The origin of the action potential in neurones has yet to be answered satisfactorily for most cells. We present here a five-conductance model of the somatic membrane of the mature and intact sympathetic neurone studied in situ in the... more
The origin of the action potential in neurones has yet to be answered satisfactorily for most cells. We present here a five-conductance model of the somatic membrane of the mature and intact sympathetic neurone studied in situ in the isolated rat superior cervical ganglion under two-electrode voltage-clamp conditions. The neural membrane hosts five separate types of voltage-dependent ionic conductances, which have been isolated at 37 degrees C by using simple manipulations such as conditioning-test protocols and external ionic pharmacological treatments. The total current could be separated into two distinct inward components: (1) the sodium current, INa, and (2) the calcium current, ICa; and three outward components: (1) the delayed rectifier, IKV, (2) the transient IA, and (3) the calcium-dependent IKCa. Each current has been kinetically characterized in the framework of the Hodgkin-Huxley scheme used for the squid giant axon. Continuous mathematical functions are now available for the activation and inactivation (where present) gating mechanisms of each current which, together with the maximum conductance values measured in the experiments, allow for a satisfactory reconstruction of the individual current tracings over a wide range of membrane voltage. The results obtained are integrated in a full mathematical model which, by describing the electrical behaviour of the neurone under current-clamp conditions, leads to a quantitative understanding of the physiological firing pattern. While, as expected, the fast inward current carried by Na+ contributes to the depolarizing phase of the action potential, the spike falling phase is more complex than previous explanations. IKCa, with a minor contribution from IKV, repolarizes the neurone only under conditions of low cell internal negativity. Their role becomes less pronounced in the voltage range negative to -60 mV, where membrane repolarization allows IA to deinactivate. In the spike arising from these voltage levels the membrane repolarization is mainly sustained by IA, which proves to be the only current sufficiently fast and large enough to recharge the membrane capacitor at the speed observed during activity. Different modes of firing coexist in the same neurone and the switching from one to another is fast and governed by the membrane potential level, which makes the selection between the different voltage-dependent channel systems. The neurone thus seems to be prepared to operate within a wide voltage range; the results presented indicate the basic factors underlying the different discrete behaviours.
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Fibroblast growth factor 2 (FGF-2) has multiple, pleiotropic effects on the nervous system that include neurogenesis, neuroprotection and neuroplasticity. Thus, alteration in FGF-2 expression patterns may have a profound impact in brain... more
Fibroblast growth factor 2 (FGF-2) has multiple, pleiotropic effects on the nervous system that include neurogenesis, neuroprotection and neuroplasticity. Thus, alteration in FGF-2 expression patterns may have a profound impact in brain function, both in normal physiology and in pathology. Here, we used FGF-2 transgenic mice (TgFGF2) to study the effects of endogenous FGF-2 overexpression on susceptibility to seizures and to the pathological consequences of seizures. TgFGF2 mice display increased FGF-2 expression in hippocampal pyramidal neurons and dentate granule cells. Increased density of glutamatergic synaptic vesicles was observed in the hippocampus of TgFGF2 mice, and electrophysiological data (input/output curves and patch-clamp recordings in CA1) confirmed an increase in excitatory inputs in CA1, suggesting the presence of a latent hyperexcitability. Indeed, TgFGF2 mice displayed increased susceptibility to kainate-induced seizures compared with wild-type (WT) littermates, ...
Research Interests: Neuroscience, Neurogenesis, Epilepsy, Biology, Medicine, and 15 moreHippocampus, Humans, Mice, Female, Animals, Male, Cell Death, Neuronal Plasticity, Fibroblast Growth Factor, Glutamic Acid, Hippocampal formation, Kainic acid, Psychology and Cognitive Sciences, Medical and Health Sciences, and Nerve degeneration
Research Interests: Neuroscience, Chemistry, Electrophysiology, Biology, Medicine, and 15 moreCerebrospinal Fluid, Glutamate, Animals, Neurons, AMPA, Glycine receptor, Membrane Potential, Neurosciences, Electric Impedance, Bicuculline, Glutamate release, Cell Membrane, GABAA receptor, In Vitro Techniques, and Activity pattern
The capacity of periglomerular cells (PGc) to give fast, Na-dependent action potentials is a crucial and debated issue for the comprehension of how sensory information is processed in the olfactory bulb (OB). Using patchclamp whole cell... more
The capacity of periglomerular cells (PGc) to give fast, Na-dependent action potentials is a crucial and debated issue for the comprehension of how sensory information is processed in the olfactory bulb (OB). Using patchclamp whole cell recording in thin slices of rat OB (P8-P20) we showed that fast sodium conductance is present in all the PGc studied, that this current is sufficiently large to generate action potentials and that action potentials can be evoked in these cells by direct stimulation of the olfactory nerve. A comprehensive kinetic characterization of INa is also presented.
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You might find this additional information useful... This article cites 35 articles, 7 of which you can access free at: http://jn.physiology.org/cgi/content/full/80/1/344#BIBL This article has been cited by 3 other HighWire hosted... more
You might find this additional information useful... This article cites 35 articles, 7 of which you can access free at: http://jn.physiology.org/cgi/content/full/80/1/344#BIBL This article has been cited by 3 other HighWire hosted articles: € [Abstract]€ [Full Text]€ J Neurophysiol, September 1,€1999; 82€(3): 1352-1362. C. J. Wierenga and W. J. Wadman Epileptogenesis Miniature Inhibitory Postsynaptic Currents in CA1 Pyramidal Neurons After Kindling€ [Abstract]€ [Full Text]€ [PDF] J. Neurosci., February 4,€2004; 24€(5): 1190-1199. A. Hayar, S. Karnup, M. T. Shipley and M. Ennis Are Entrained by Patterned Olfactory Input Olfactory Bulb Glomeruli: External Tufted Cells Intrinsically Burst at Theta Frequency and€ [Abstract]€ [Full Text]€ [PDF] Physiol Rev, January 1,€2005; 85€(1): 281-317. P.-M. Lledo, G. Gheusi and J.-D. Vincent Information Processing in the Mammalian Olfactory System on the following topics: Medline items on this article's topics can be found at http://highwire.st...
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Thin slices were prepared from cerebella of 10-24 day old rats and examined with whole-cell patch-clamp methods. Depolarizing steps from holding potentials negative to -60 mV elicited an early transient outward current, identified as IA,... more
Thin slices were prepared from cerebella of 10-24 day old rats and examined with whole-cell patch-clamp methods. Depolarizing steps from holding potentials negative to -60 mV elicited an early transient outward current, identified as IA, and a late outward K+ current. Depolarizations from -50 mV failed to evoke any A current and gave only a slowly rising component similar to the delayed K+ current, which inactivated thereafter with a time constant of 2.5 s at -30 mV. The IA peaked in 1-2 ms, decayed following a double exponential with time constants of 8.1 and 53.2 ms at +20 mV and was half-inactivated at -82.5 mV. 4-AP 4 mM depressed both K+ currents showing little specificity between them, while TEA 20 mM selectively abolished only the delayed K+ current.
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Some years ago Greengard and coworkers (5–7) put forward a comprehensive hypothesis to explain the genesis of the slow synaptic potentials observed in curarized mammalian sympathetic ganglia after tetanization of preganglionic fibers.... more
Some years ago Greengard and coworkers (5–7) put forward a comprehensive hypothesis to explain the genesis of the slow synaptic potentials observed in curarized mammalian sympathetic ganglia after tetanization of preganglionic fibers. Following this hypothesis the slow synaptic potentials were due to an increase of cyclic nucleotides levels brought about by the interaction of either acetylcholine (ACh)(slow EPSP) or dopamine (DA)(slow IPSP) with specific receptors located on ganglion neuron membranes. In particular, according to Greengard’s hypothesis, prostaglandin E1 (PGE1) would act as a DA antagonist reducing the amplitude of the slow IPSP extracellularly recorded from isolated ganglion preparations. Since DA was supposed to increase cAMP levels via activation of adenylate cyclase, PGE1 would exert an inhibitory action on this enzyme.
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Whole-cell patch-clamp recordings were carried out in visually identified periglomerular and external tufted cells of rat olfactory bulb. Most of the neurones showed a slowly developing hyperpolarisation-activated current with a threshold... more
Whole-cell patch-clamp recordings were carried out in visually identified periglomerular and external tufted cells of rat olfactory bulb. Most of the neurones showed a slowly developing hyperpolarisation-activated current with a threshold generally positive to resting potential and with a strongly voltage-dependent activation time constant. The current, identified as Ih, was sodium- and potassium-sensitive, suppressed by external caesium, and insensitive to barium. Under current-clamp conditions, perfusion with caesium induced a 10 mV hyperpolarisation and a marked reduction of the rate of low-frequency oscillations induced experimentally. It is concluded that most of the cells in the rat glomerular layer present a distinct h-current, which is tonically active at rest and which may contribute to the oscillatory behaviour of the bulbar network.
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Whole-cell patch-clamp recordings were carried out in visually identified periglomerular and external tufted cells of rat olfactory bulb. Most of the neurones showed a slowly developing hyperpolarisation-activated current with a threshold... more
Whole-cell patch-clamp recordings were carried out in visually identified periglomerular and external tufted cells of rat olfactory bulb. Most of the neurones showed a slowly developing hyperpolarisation-activated current with a threshold generally positive to resting potential and with a strongly voltage-dependent activation time constant. The current, identified as Ih, was sodium- and potassium-sensitive, suppressed by external caesium, and insensitive to barium. Under current-clamp conditions, perfusion with caesium induced a 10 mV hyperpolarisation and a marked reduction of the rate of low-frequency oscillations induced experimentally. It is concluded that most of the cells in the rat glomerular layer present a distinct h-current, which is tonically active at rest and which may contribute to the oscillatory behaviour of the bulbar network.
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The patch-clamp technique was applied to periglomerular (PG) cells from slices of frog and rat olfactory bulbs to characterize whole cell and single-channel properties of inhibitory synaptic currents. Spontaneous and electrically driven... more
The patch-clamp technique was applied to periglomerular (PG) cells from slices of frog and rat olfactory bulbs to characterize whole cell and single-channel properties of inhibitory synaptic currents. Spontaneous and electrically driven bicuculline-sensitive synaptic events were recorded under ionic conditions that excluded any possible interference of excitatory synapses. The peak amplitude distribution of spontaneous events could be fitted by several Gaussians having the same interpeak distance. Spontaneous currents reversed polarity at the chloride equilibrium potential and were suppressed by 2 mM Co2+; the decay phase could be fitted with a single exponential having a time constant of approximately 10 ms at 0 mV. Bicuculline-sensitive monosynaptic responses could be evoked in PG cells by electrical stimulations delivered at the distance of several glomeruli within the glomerular layer. Finally, in excised outside-out patches, single-channel analysis revealed the presence of typi...
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Research Interests: Electrophysiology, Patch-clamp and imaging techniques, Biological Sciences, Dopamine, Mice, and 12 moreAnimals, Acetylcholine, Potassium, Green Fluorescent Protein, Tyrosine Hydroxylase, Perforation, Chemical Senses, Olfactory Bulb, Membrane Potential, Second Messengers, Interneurons, and Patch Clamp
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1. Whole-cell voltage-clamp techniques were used to study voltage-activated transient potassium currents in a large sample (n = 143) of granule cells (GrC) from rat cerebellar slices. Tetrodotoxin (TTX; 0.1 microM) was used to block... more
1. Whole-cell voltage-clamp techniques were used to study voltage-activated transient potassium currents in a large sample (n = 143) of granule cells (GrC) from rat cerebellar slices. Tetrodotoxin (TTX; 0.1 microM) was used to block sodium currents, while calcium current was too small to be seen under ordinary conditions. 2. Depolarizing pulses from -50 mV evoked a slow, sustained outward current, developing with a time constant of 10 ms, inactivating over a time scale of seconds and which could be suppressed by 20 mM tetraethylammonium (TEA). By preventing the Ca2+ inflow, this slow outward current could be further separated into a Ca(2+)-dependent and a Ca(2+)-independent component. 3. After conditioning hyperpolarizations to potentials negative to -60 mV, depolarizations elicited transient outward current, peaking in 1-2 ms and inactivating rapidly (approximately 10 ms at 20 degrees C), showing the overall kinetic characteristics of the A-current (IA). The current activated following third-order kinetics and showed a maximal conductance of 12 nS per cell, corresponding to a normalized conductance of 3.8 nS/pF. 4. IA was insensitive to TEA and to the Ca(2+)-channel blockers. 4-Aminopyridine (4-AP) reduced the A-current amplitude by approximately 20%, and the delayed outward currents by > 80%. 5. Voltage-dependent steady-state inactivation of peak IA was described by a Boltzmann function with a slope factor of 8.4 mV and half-inactivation occurring at -78.8 mV. Activation of IA was characterized by a Boltzmann curve with the midpoint at -46.7 mV and with a slope factor of 19.8 mV. 6. IA activation and inactivation was best fitted by the Hodgkin-Huxley m3h formalism. The rate of activation, tau a, was voltage-dependent, and had values ranging from 0.55 ms at -40 mV to 0.2 ms at +50 mV. Double-pulse experiment showed that development and removal of inactivation followed a single-exponential time course; the inactivation time constant, tau ha, was markedly voltage-dependent and ranged from approximately 10 ms at -40 and -100 mV and 70 ms at -70 mV. 7. A set of continuous equations has been developed describing the voltage-dependence of both the steady-state and time constant of activation and inactivation processes, allowing a satisfactory numerical reconstruction of the A-current over the physiologically significant membrane voltage range.(ABSTRACT TRUNCATED AT 400 WORDS)
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Whole-cell patch clamp recording techniques were applied to periglomerular (PG) cells in slices of the frog olfactory bulb (OB) to study the properties of the excitatory synapses in the triad formed by the olfactory nerve (ON) and the... more
Whole-cell patch clamp recording techniques were applied to periglomerular (PG) cells in slices of the frog olfactory bulb (OB) to study the properties of the excitatory synapses in the triad formed by the olfactory nerve (ON) and the dendrites of mitral/tufted (MT) cells and PG cells. The postsynaptic response evoked by ON stimulation was glutamatergic and could be dissected into NMDA and non-NMDA components of equivalent amplitudes. The dendro-dendritic synapse between MT and PG cells could be activated following antidromic stimulation of the lateral and medial olfactory tract (LOT and MOT). In this case the postsynaptic potentials had amplitudes and durations comparable to those obtained by ON stimulation, the neurotransmitter was glutamate, but the synapse was largely dominated by the slow NMDA component.
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Research Interests: Cognitive Science, Electrophysiology, Nonparametric Statistics, Calcium, Patch-clamp and imaging techniques, and 21 moreDopamine, Glutamate, Brain, Mice, Animals, Metabotropic Glutamate Receptors, Synaptic Transmission, Neurons, Olfactory Bulb, Action potential, Glycine, Acetic Acid, Membrane Potential, Action Potentials, Voltage Clamp, L, Neurosciences, Glutamic Acid, Patch Clamp, Glutamate Receptor, and Phospholipase C
Research Interests: Electrophysiology, Stem Cells, Immunohistochemistry, Stem Cell, Patch-clamp and imaging techniques, and 19 moreCell Differentiation, Glutamate receptors, GABA receptors, Female, Animals, Male, The, Neurons, Rats, Voltage-Gated Potassium Channels, Potassium Channels, Olfactory Bulb, Wistar Rats, Synaptic Integration, Subventricular Zone, Interneurons, Glutamic Acid, Patch Clamp, and Glutamate Receptor
Thin slices were prepared from cerebella of 10-24 day old rats and examined with whole-cell patch-clamp methods. Depolarizing steps from holding potentials negative to -60 mV elicited an early transient outward current, identified as IA,... more
Thin slices were prepared from cerebella of 10-24 day old rats and examined with whole-cell patch-clamp methods. Depolarizing steps from holding potentials negative to -60 mV elicited an early transient outward current, identified as IA, and a late outward K+ current. Depolarizations from -50 mV failed to evoke any A current and gave only a slowly rising component similar to the delayed K+ current, which inactivated thereafter with a time constant of 2.5 s at -30 mV. The IA peaked in 1-2 ms, decayed following a double exponential with time constants of 8.1 and 53.2 ms at +20 mV and was half-inactivated at -82.5 mV. 4-AP 4 mM depressed both K+ currents showing little specificity between them, while TEA 20 mM selectively abolished only the delayed K+ current.
Dopaminergic (DA) periglomerular (PG) neurons are critically placed at the entry of the bulbar circuitry, directly in contact with both the terminals of olfactory sensory neurons and the apical dendrites of projection neurons; they are... more
Dopaminergic (DA) periglomerular (PG) neurons are critically placed at the entry of the bulbar circuitry, directly in contact with both the terminals of olfactory sensory neurons and the apical dendrites of projection neurons; they are autorhythmic and are the target of numerous terminals releasing a variety of neurotransmitters. Despite the centrality of their position, suggesting a critical role in the sensory processing, their properties -and consequently their function- remain elusive. The current mediated by inward rectifier potassium (Kir) channels in DA-PG cells was recorded by adopting the perforated-patch configuration in thin slices; IKir could be distinguished from the hyperpolarization-activated current (I h ) by showing full activation in <10 ms, no inactivation, suppression by Ba(2+) in a typical voltage-dependent manner (IC50 208 μM) and reversal potential nearly coincident with EK. Ba(2+) (2 mM) induces a large depolarization of DA-PG cells, paralleled by an incre...
The subventricular zone produces neuroblasts that migrate to the olfactory bulb (OB) and differentiate into interneurons throughout postnatal life (Altman and Das, 1966; Hinds, 1968; Altman, 1969; Kishi et al., 1990; Luskin, 1993; Lois... more
The subventricular zone produces neuroblasts that migrate to the olfactory bulb (OB) and differentiate into interneurons throughout postnatal life (Altman and Das, 1966; Hinds, 1968; Altman, 1969; Kishi et al., 1990; Luskin, 1993; Lois and Alvarez-Buylla, 1994). Although such postnatally generated interneurons have been characterized morphologically, their physiological differentiation has not been thoroughly described. Combining retroviral-mediated labeling of newly generated neurons with patch-clamp electrophysiology, we demonstrated that soon after new cells enter the layers of the olfactory bulb, they display voltage-dependent currents typical of more mature neurons. We also show that these "newcomers" express functional GABA and glutamate receptor channels, respond synaptically to stimulation of the olfactory nerve, and may establish both axodendritic and dendrodendritic synaptic contacts within the olfactory bulb. These data provide a basic description of the physiol...
Research Interests: Electrophysiology, Stem Cells, Immunohistochemistry, Stem Cell, Patch-clamp and imaging techniques, and 19 moreCell Differentiation, Glutamate receptors, GABA receptors, Female, Animals, Male, The, Neurons, Rats, Voltage-Gated Potassium Channels, Potassium Channels, Olfactory Bulb, Wistar Rats, Synaptic Integration, Subventricular Zone, Interneurons, Glutamic Acid, Patch Clamp, and Glutamate Receptor
Whole-cell patch clamp recording techniques were applied to periglomerular (PG) cells in slices of the frog olfactory bulb (OB) preparation to study the basic electrical properties of these inhibitory interneurons. The cells were... more
Whole-cell patch clamp recording techniques were applied to periglomerular (PG) cells in slices of the frog olfactory bulb (OB) preparation to study the basic electrical properties of these inhibitory interneurons. The cells were intracellularly stained with Lucifer Yellow for precise identification. Under current-clamp conditions PG cells showed rich spontaneous excitatory synaptic activity at rest, usually leading to overshooting, TTX-sensitive action potentials. The passive cable properties of the cell membrane have been carefully characterised. Depolarisation of this neurone under voltage-clamp conditions activated a complex pattern of current flow, that has been dissected into its main components. The currents have been isolated resorting to their different kinetic and pharmacological properties. Four main voltage dependent ionic currents have been isolated, two inward currents, I(Na) and I(Ca), and two outward currents carried by potassium ions, one fast transient, I(A)-type a...
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The effect of Zn2+ 100 microM-1 mM has been studied on the kinetics of the A-current in granule cells from rat cerebellar slices using the patch-clamp technique in the whole-cell configuration. Zn2+ induced marked shifts towards positive... more
The effect of Zn2+ 100 microM-1 mM has been studied on the kinetics of the A-current in granule cells from rat cerebellar slices using the patch-clamp technique in the whole-cell configuration. Zn2+ induced marked shifts towards positive potentials of both the activation and inactivation steady-state curves, a reduction of maximal amplitude and a slowing of the activation kinetics, leaving unaffected the inactivation time constants. These modifications cannot be explained in terms of the screening of the negative surface charges, but are probably due to a direct action on the A-channel. The alterations observed in the IA kinetics could be of physiological relevance in some neurological disorders for which significant increase of the Zn2+ levels in the cerebrospinal fluid have been described.
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1. The electrophysiological effects of a pumiliotoxin-B-like alkaloid extracted from the skin of the Australian frog Pseudophryne coriacea (PsC) have been studied in rat superior cervical ganglia at 37 degrees C. 2. PsC (50 mg/ml) elicits... more
1. The electrophysiological effects of a pumiliotoxin-B-like alkaloid extracted from the skin of the Australian frog Pseudophryne coriacea (PsC) have been studied in rat superior cervical ganglia at 37 degrees C. 2. PsC (50 mg/ml) elicits a broadening of the evoked compound action potential and, at rest, the appearance of spontaneous spike discharge at 10-20 Hz. Action potentials presumably originate far away from the soma, which is invaded in a typical IS-SD sequence. 3. The toxin effect is not related to any direct action on the preganglionic fibers of the sympathetic trunk, and does not involve synaptic mechanisms. 4. Two-electrode voltage-clamp experiments showed that the main properties of the major voltage-dependent ionic currents are apparently unaffected by the toxin, while the cell input resistance is considerably reduced. 5. The data are consistent with the hypothesis that PsC elicits a cationic permeability increase generating a pacemaker current in a region close to the ...
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ABSTRACT Neurogenesis is the process by which cells divide, migrate, and subsequently differentiate into a neuronal phenotype. Significant rates of neurogenesis persist into adulthood in two brain regions, the subgranular zone of the... more
ABSTRACT Neurogenesis is the process by which cells divide, migrate, and subsequently differentiate into a neuronal phenotype. Significant rates of neurogenesis persist into adulthood in two brain regions, the subgranular zone of the dentate gyrus and the subventricular zone of the lateral ventricles. Cells of the subventricular zone divide and migrate via the rostral migratory stream to the olfactory bulb where they differentiate into granule and periglomerular cells. With the discovery of large-scale neurogenesis in the adult brain, there have been significant efforts to identify the mechanisms that control this process as well as the role of these cells in neuronal functioning. Although many questions remain unanswered, new insights appear daily about adult neurogenesis, regulatory mechanisms, and the fates of the progeny. In this review we highlight the main studies investigating factors that regulate neurogenesis in the subventricular zone, neuronal migration to the olfactory bulb, neuronal integration into the existing bulbar network and shortly discuss the functional meaning of this process.
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Adult mesenchymal stem cells derived from adipose tissue (A-MSC) have the capacity to differentiate in vitro into mesenchymal as well as endodermal and ectodermal cell lineages. We investigated the neuronal differentiation potential of... more
Adult mesenchymal stem cells derived from adipose tissue (A-MSC) have the capacity to differentiate in vitro into mesenchymal as well as endodermal and ectodermal cell lineages. We investigated the neuronal differentiation potential of human A-MSC with a protocol which included sphere formation and sequential culture in brain-derived neurotrophic factor (BDNF) and retinoic acid (RA). After 30 days, about 57% A-MSC showed morphological, immunocytochemical and electrophysiological evidence of initial neuronal differentiation. In fact, A-MSC displayed elongated shape with protrusion of two or three cellular processes, selectively expressed nestin and neuronal molecules (including GABA receptor and tyroxine hydroxilase) in the absence of glial phenotypic markers. Differentiated cells showed negative membrane potential (-60 mV), delayed rectifier potassium currents and TTX-sensitive sodium currents. Such changes were stable for at least 7 days after removal of differentiation medium. In view of these results and the easy availability of adipose tissue, A-MSC may be a ready source of adult MSC with neuronal differentiation potential, an useful tool to treat neurodegenerative diseases.