Biomedical subjects

F Tell

Publications and source records attributed to F Tell.

14 recordsLinked to original sources

PubMed2004

N-methyl-d-aspartate receptor activation exerts a dual control on postnatal development of nucleus tractus solitarii neurons in vivo.

We have used a morphological approach to evaluate the role of NMDA receptors (NMDAR) in postnatal development of brainstem neurons in awake rats. Chronic NMDAR blockade was performed by placing drug-impregnated Elvax implants over the brainstem at the fifth postnatal day (P5). Compared with control, NMDAR blockade led to a transient increase in dendritic arbor area and filopodium density until P12 followed by a rapid decline in both parameters. Electron microscopy observations showed that these changes correlated with an increase in synapse density at P14 followed by a decrease in synapse density at P28 if chronic NMDAR blockade was maintained until P21. These results support the hypothesis that synapse formation does not require NMDAR activation. In addition, our data suggest a dual role for NMDAR in controlling the synapse number. Early in development NMDARs may be involved in controlling the rate of synapse elimination. Later on, they may subserve synapse stabilization. The physiological significance of these results is discussed.

Animals↗

PubMed2001

NMDA receptor and nitric oxide synthase activation regulate polysialylated neural cell adhesion molecule expression in adult brainstem synapses.

Here we report that synapses in the adult dorsal vagal complex, a gateway for many primary afferent fibers, express a high level of the polysialylated neural cell adhesion molecule (PSA-NCAM). We show that electrical stimulation of the vagal afferents causes a rapid decrease of PSA-NCAM expression both in vivo and in acute slices. Inhibition of NMDA receptor activity completely prevented the decrease. Blockade of calmodulin activation, neuronal nitric oxide (NO) synthase, or soluble guanylyl cyclase and chelation of extracellular NO mimicked this inhibition. Our data provide a mechanistic framework for understanding how activity-linked stimulation of the NMDA-NO-cGMP pathway induces rapid changes in PSA-NCAM expression, which may be associated with long-term depression.

Animals↗

PubMed2001

Perinatal changes of I(h) in phrenic motoneurons.

The hyperpolarization-activated cationic current (I(h)) was characterized and its maturation studied on phrenic motoneurons (PMNs), from reduced preparations of foetal (E18 and E21) and newborn (P0-P3) rats, using the whole-cell patch-clamp technique. In voltage-clamp mode, 2-s hyperpolarizing steps (5-mV, -50 to -110 mV) elicited a noninactivating inward current, blocked by external application of Cs+ or ZD 7288. At -110 mV, Ih current density averaged 0.67 +/- 0.41 pA/pF at E18, reached a transient peak at E21 (1.38 +/- 0.11 pA/pF) and decreased at P0-P3 (0.77 +/- 0.22 pA/pF). V1/2 was similar at E18 and E21 (-79 mV) but was significantly hyperpolarized at P0-P3 (-90 mV). The time constant of activation was voltage-dependent, and significantly faster at E21. Reversal potential was similar at all ages when estimated by extrapolation or tail current procedures. It was positively shifted by 25 +/- 6 mV when external potassium was raised from 3 to 10 m M, suggesting a similar sensitivity to K+ from E18 to P0-3. Cs(+) or ZD 7288 applications on PMNs at rest in current-clamp mode, in a partitioned chamber, induced a 10 +/- 2 mV hyperpolarization at E18 and E21, and an 8 +/- 2 mV hyperpolarization at P0-3. The area of the central respiratory drive potential or current was increased by 33 and 31%, respectively, at E21, but was not significantly modified at E18 and P0-3. Our data suggest a critical period during the perinatal maturation of Ih during which it is transiently upregulated and attenuates the influence of the central respiratory drive on PMNs just prior to birth.

Animals↗

PubMed2001

Dual effects of NMDA receptor activation on polysialylated neural cell adhesion molecule expression during brainstem postnatal development.

Here we show a dual role of N-methyl-d-aspartate receptor (NMDAR) activation in controlling polysialylated neural cell adhesion molecule (PSA-NCAM) dynamic expression in the dorsal vagal complex (DVC), a gateway for many primary afferent fibres. In this structure the overall expression of PSA-NCAM decreases during the first 2 weeks after birth to persist only at synapses in the adult. Electrical stimulation of the vagal afferents causes a rapid increase of PSA-NCAM expression both in vivo and in acute slices before postnatal day (P) 14 whereas a similar stimulation induces a decrease after P15. Inhibition of NMDAR activity in vitro completely prevented these changes. These regulations depend on calmodulin activation and cGMP production at all stages. By contrast, blockade of neuronal nitric oxide synthase (nNOS) prevented these changes only after P10 in agreement with its late expression in the DVC. The pivotal role of NMDAR is also supported by the observation that chronic blockade induces a dramatic decrease in PSA-NCAM expression.

Aging↗

PubMed2000

Cellular and synaptic effect of substance P on neonatal phrenic motoneurons.

Experiments were carried out on the in vitro brainstem-spinal cord preparation of the newborn rat to analyse the effects of substance P (SP) on phrenic motoneuron (PMN) activity. In current-clamp mode, SP significantly depolarized PMNs, increased their input resistance, decreased the rheobase current and shifted the firing frequency-intensity relationships leftwards, but did not affect spike frequency adaptation or single spike configuration. The neurokinin receptor agonist NK1 had SP-mimetic effects, whereas the NK3 and NK2 receptor agonists were less effective and ineffective, respectively. In a tetrodotoxin-containing aCSF, only SP or the NK1 receptor agonist were still active. No depolarization was observed when the NK1 receptor agonist was applied in the presence of muscarine. In voltage-clamp mode, SP or the NK1 receptor agonist produced an inward current (ISP) which was not significantly reduced by extracellular application of tetraethylammonium, Co2+, 4-aminopyridine or Cs+. In aCSF containing tetrodotoxin, Co2+ and Cs+, ISP was blocked by muscarine. No PMN displayed any M-type potassium current but only a current showing no voltage sensitivity over the range -100 to 0 mV, reversing near the expected EK +, hence consistent with a leak current. SP application to the spinal cord only (using a partitioned chamber) significantly increased the phrenic activity. Pretreatment with the NMDA receptor antagonist DL-2-amino-5-phosphonovaleric acid (AP5) decreased the C4 discharge duration and blocked the effect of SP, thus exhibiting an NMDA potentiation by SP. In conclusion, SP modulates postsynaptically the response of phrenic motoneurons to the inspiratory drive through the reduction of a leak conductance and the potentiation of the NMDA component of the synaptic input.

2-Amino-5-phosphonovalerate↗

PubMed1999

Postnatal development of rat nucleus tractus solitarius neurons: morphological and electrophysiological evidence.

Postnatal development of neurons in the caudal nucleus tractus solitarii of rats was studied using the Golgi-Cox technique and whole-cell recordings. Two cell classes were defined on the basis of somatic and dendritic morphology. Elongated neurons have two thick primary dendrites originating from the long axis of the soma. The primary dendrites, tapering distally, give rise to one to four secondary dendrites. Multipolar neurons have pyramidal somas. Extending from each apex of the cell body was a long primary dendrite, which gave rise to a variable number of secondary dendrites. The relative proportion of the two classes was rather constant from birth to adulthood. During the first two postnatal weeks, dendritic length and area of influence increase, but neuronal geometry is not altered in either class. Dendritic appendages appear by postnatal day 5, reach a peak at postnatal day P12 and then almost disappear in adult neurons. Combined intracellular injection of neurobiotin and whole-cell recordings indicate that morphological alteration of caudal nucleus tractus solitarius neurons occurs in parallel with changes in passive properties and spike characteristics. However, the firing pattern of discharge is not correlated with morphology. The physiological significance of these results is discussed.

Animals↗

PubMed1997

Postnatal changes in electrophysiological properties of rat nucleus tractus solitarii neurons.

Whole-cell recordings in brainstem slices revealed postnatal changes in passive and firing properties in the rat caudal nucleus tractus solitarii (cNTS) neurons. Membrane potential, threshold for Na+ spike and degree of sag were unchanged during development. In the adult, the rheobase was twice that found at birth. The input resistance decreased over the period studied, while time constants declined markedly after the third postnatal week. At all postnatal ages, Na(+)-dependent action potentials (APs) were elicited in response to depolarization. Nevertheless, AP duration gradually decreased by 40% over the developmental period studied. Spike amplitude was smaller at birth than at any other ages and reached a peak two weeks after birth. At all ages, Na(+)-dependent APs were blocked by application of tetrodotoxin. Full APs were replaced by an initial slow oscillation in young cells and by oscillations in older cells. The TTX-resistant oscillations were altered by cobalt (2 mM) and cadmium (100 microM). The spike afterhyperpolarization (AHP) was not altered during development, but was observed in less neurons in adult cells when measured at a holding potential of -60 mV. Neurons were subdivided into one of three classes based on their responses to a hyperpolarizing prepulse: 1) post-inhibitory rebound (PIR) cells, 2) delayed excitation (DE) cells and 3) NON cells expressing neither PIR nor DE. The relative proportions of different cell types varied with age. The mean maximum duration of DE increased three times. Voltage-clamp experiments revealed that the DE was due to the activation of an A-current. In addition, a three-fold increase in its inactivation rate was observed postnatally. The physiological significance of these results is discussed.

Action Potentials↗

PubMed1996

Perinatal developmental changes in respiratory activity of medullary and spinal neurons: an in vitro study on fetal and newborn rats.

Experiments were performed in vitro on fetal and newborn rat brainstem-spinal cord preparations to analyse the perinatal developmental changes in inspiratory motor output. The amplitude of the inspiratory bursts of the whole C4 ventral root (global extracellular recording), the firing patterns of 80 medullary inspiratory neurons (unitary extracellular recording) and the firing and membrane properties of 71 respiratory neurons in the C4 ventral horn (whole-cell recording) were analysed at embryonic day 18 (E18), 21 (E21) and post natal days 0 to 3 (P0-3). At E18, the amplitude of the C4 bursts was weak and variable from one respiratory cycle to the next, as well as the discharge pattern of most of the medullary inspiratory neurons. C4 motoneurons were immature, very excitable and displaying variable inspiratory discharges, but already able to deliver sustained bursts of potentials when depolarised. At E21 and P0-3, the amplitude of the C4 bursts was increased and stable, most of the medullary inspiratory neurons already were able to generate a stable firing pattern and C4 motoneurons showed maturational changes in terms of the resting potential, spike amplitude and input membrane resistance. This work suggests that the short period extending from E18 to E21 is a critical maturational period for the medullary respiratory network which becomes able to elaborate a stable respiratory motor output.

Action Potentials↗

PubMed1996

Developmental study of N-methyl-D-aspartate-induced firing activity and whole-cell currents in nucleus tractus solitarii neurons.

Whole-cell recordings of rat nucleus tractus solitarii (NTS) neurons were performed on a slice preparation. We investigated possible postnatal changes in firing activities and currents induced by N-methyl-D-aspartate (NMDA) application. A total of 42 neurons were selected and fell into the following age groups: 0-5 days (n = 15), 10-15 days (n = 9) and 30-60 days (adult, n = 18). During this period, input resistance and spike duration decreased by approximately 40%. At all ages, bath application of NMDA elicited a bursting firing activity when the membrane potential was held between -60 and -75 mV. However, in the youngest cells the rhythmic bursting activity was irregular and was characterized by a progressive firing inactivation during a burst. In a tetrodotoxin-containing saline, NMDA-induced oscillations of membrane potential were retained in all age groups. The membrane current-voltage relationship of the NMDA-induced inward current (INMDA) was characterized by a region of negative slope conductance which was similar in all age groups. Thus the voltage-dependent block of INMDA is present in NTS neurons from birth, allowing NTS neurons to display membrane potential oscillations. However, postnatal maturation of repolarizing conductances, as suggested by changes in spike characteristics, could render the oscillatory activity more stable than at birth.

Aging↗

PubMed1994

Whole-cell analysis of ionic currents underlying the firing pattern of neurons in the gustatory zone of the nucleus tractus solitarii.

1. Previous work from this laboratory has shown that rostral nucleus tractus solitarii (rNTS) neurons can be separated into four different classes on the basis of responses to a current injection paradigm consisting of membrane hyperpolarization immediately followed by a depolarizing pulse. These classes have been termed Group I, II, III, and IV neurons. The regular repetitive firing discharge pattern of Group I cells is changed into an irregular spike train by membrane hyperpolarization. Hyperpolarization of Group II neurons delays the firing discharge induced by depolarization. Hyperpolarization had the least effect on the discharge pattern of Group III neurons. The discharge pattern of Group IV neurons consisted of a short burst of spikes. We used whole-cell recordings and pharmacological channel blockers in an in vitro brain stem slice preparation to determine the ionic basis for the repetitive firing properties of rNTS neurons. 2. Application of 4-aminopyridine (4-AP, 1 mM) decreased input resistance and increased action potential duration in all groups of neurons. However, the discharge pattern of Group I, III, and IV neurons was either unaltered or slightly modified by 4-AP. In contrast the delay in firing of Group II cells induced by hyperpolarization was strongly reduced and in some cases completely suppressed by application of 4-AP. This suggests that a 4-AP-sensitive conductance primarily underlies the firing pattern of Group II cells. 3. Voltage-clamp recordings revealed that the delay in Group II neurons is due to a transient outward potassium current that is partially inactivated around the resting membrane potential. Hyperpolarization removed this inactivation, causing a delay in the firing of the cell. The potassium current was blocked by 4-AP. A similar current was occasionally seen in neurons of the other groups. On the basis of its voltage and pharmacological dependence this current was presumed to be an A-current (IKA). 4. Blockade of calcium currents by a low-calcium (0.5 mM) saline containing 2 mM Co2+ depressed the excitability of rNTS cells. For Group II neurons the delay in firing activity was increased. In the other groups the repetitive firing pattern was suppressed. In addition the amplitude of the afterhyperpolarization occurring after a short train of action potentials was substantially reduced. This indicates that calcium currents (ICa) and calcium-activated potassium currents (IKCa) contribute to the repetitive firing properties of rNTS neurons. 5. In about half of Group I, III, and IV neurons an additional property was found.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗

PubMed1993

Ionic basis for endogenous rhythmic patterns induced by activation of N-methyl-D-aspartate receptors in neurons of the rat nucleus tractus solitarii.

1. Activation of N-methyl-D-aspartate (NMDA) receptors in caudal nucleus tractus solitarii (cNTS) neurons elicited endogenous rhythmic activities. We used an in vitro brain stem slice preparation to determine the ionic mechanisms underlying the generation of these activities. 2. Using intracellular recordings, we found several ionic conductances to be responsible for the electrophysiological properties of cNTS neurons. After addition of tetrodotoxin (TTX) to the perfusate, cNTS neurons were still able to generate action potentials (APs). Because these APs were suppressed by the addition of cobalt or by the reduction of calcium, they were likely due to calcium currents (ICa). In addition, the amplitude of the afterhyperpolarization (AHP) that followed a train of TTX-resistant APs was reduced in both low-calcium and cobalt-containing saline. It was therefore suggested that calcium-activated potassium (IKCa) currents were involved in the AHP. Accordingly, application of apamin, a blocker of slow IKCa, also decreased the AHP. cNTS neurons exhibited a delayed excitation phenomenon, characterized by a ramplike depolarization that delayed the onset of neuronal firing, when they were depolarized from hyperpolarizing potential. The underlying current was presumed to be an A-current (IKA), because this phenomenon was suppressed during application of 4-aminopyridine (4-AP). 3. Application of NMDA elicited different types of discharge patterns in cNTS neurons: a repetitive firing at depolarized levels of membrane potential (above -60 mV) and rhythmic patterns characterized by either rhythmic bursting or rhythmic single discharges at hyperpolarized levels (within membrane potential range of -60 to -85 mV). In all neurons, rhythmic patterns were superimposed on oscillations of membrane potential. They were characterized by a sudden shift of membrane potential, followed by a ramp-shaped phase of depolarization that preceded spike elicitation. Addition of TTX to the saline did not suppress NMDA-induced oscillations. Therefore rhythmic patterns were not driven by synaptic mechanisms but resulted from endogenous properties of cNTS neurons. 4. APs superimposed on NMDA-induced depolarizations presented the same characteristics as those elicited by positive current pulses. NMDA-elicited oscillations of membrane potential were eliminated by removing magnesium from the saline. Therefore oscillation generation was based primarily on the NMDA channel properties. 5. Intrinsic conductances of cNTS neurons interacted with NMDA-gated conductances to shape the depolarization waveform. Because removal of calcium from the saline suppressed endogenous oscillations, ICa currents were required for the expression of rhythmic activities. IKCa currents were involved in the repolarization phase of oscillations because apamin increased the duration of the oscillations.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed1991

Bursting discharges evoked in vitro, by solitary tract stimulation or application of N-methyl-D-aspartate, in neurons of the rat nucleus tractus solitarii.

Extracellular recordings of the activity of neurons in the isolated nucleus tractus solitarii (NTS) showed that repetitive stimulation of the tractus solitarius (TS) elicited either long-lasting discharges at low frequency (type A neurons) or short-duration bursting discharges at low or high frequency (type B and C neurons, respectively). Bath application of N-methyl-D-aspartate (NMDA; 60-120 microM; 4-5 min duration) elicited a pattern of rhythmic bursting in most type B (21/24) and in all type C neurons and only a repetitive firing in type A neurons, even with applications of longer duration (6-10 min). The rhythmic bursting pattern was characterized by trains of action potentials occurring at a regular rate with each neuron (mean = 0.9 +/- 0.45 Hz). The present findings suggest that local mechanisms within the NTS (synaptic interactions or neuronal intrinsic properties) are involved in the burst firing elicited either by TS stimulation or NMDA application. The data are discussed in terms of the generation of swallowing taking into account the key role of NTS neurons in the organization of this motor pattern.

Action Potentials↗

PubMed1990

Rhythmic bursting patterns induced in neurons of the rat nucleus tractus solitarii, in vitro, in response to N-methyl-D-aspartate.

The activity of nucleus tractus solitarii (NTS) neurons was recorded extracellularly on rat brainstem slices. Depending on the neuron, bath application of N-methyl-D-aspartate (NMDA; 30-120 microM) elicited either a pattern of rhythmic bursting or repetitive firing. The rhythmic bursting pattern was characterized by trains of action potentials occurring at a rate of 0.36-2 Hz. With most of the neurons, the mean burst duration and the mean discharge frequency ranged between 200 and 800 ms and between 20 and 40 Hz, respectively. Both the repetitive and the rhythmic bursting patterns were reversibly blocked when DL-2-amino-5-phosphonovalerate (80 microM) was applied. Application of quisqualate (30-60 microM) or glutamate (300-1200 microM) on NTS neurons induced only repetitive firing even in neurons exhibiting a rhythmic bursting pattern under NMDA. The present findings show that rhythmic bursting patterns can be generated within the isolated NTS under activation of NMDA receptors. The rhythmic bursting resulted probably from local NTS mechanisms (synaptic interactions or neuronal intrinsic properties) which might be involved in physiological rhythmic activities organized at the NTS level, such as swallowing.

2-Amino-5-phosphonovalerate↗

PubMed1990

Neurons of the nucleus tractus solitarius, in vitro, generate bursting activities by solitary tract stimulation.

Extracellular recordings of the activity of nucleus tractus solitarius (NTS) neurons were performed on rat brainstem slice preparations. Neurons localized in the medial part of the lateral NTS, which displayed a synaptic response to single pulse stimulation of the tractus solitarius (TS), generated bursting activity following repetitive TS stimulation (20-50 Hz frequency, 100-600 ms duration). According to their patterns of discharge and to the duration and frequency of their bursting activities, these neurons were classified in three groups called type A, B and C. We suggest that different cellular intrinsic properties, rather than local synaptic interactions, might be involved in the generation of these three types of bursting activities. These results are discussed in terms of the role of NTS neurons in the generation of the swallowing motor pattern.

Action Potentials↗