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J Tabak

Publications and source records attributed to J Tabak.

14 recordsLinked to original sources
PubMed2001

The role of activity-dependent network depression in the expression and self-regulation of spontaneous activity in the developing spinal cord.

Spontaneous episodic activity occurs throughout the developing nervous system because immature circuits are hyperexcitable. It is not fully understood how the temporal pattern of this activity is regulated. Here, we study the role of activity-dependent depression of network excitability in the generation and regulation of spontaneous activity in the embryonic chick spinal cord. We demonstrate that the duration of an episode of activity depends on the network excitability at the beginning of the episode. We found a positive correlation between episode duration and the preceding inter-episode interval, but not with the following interval, suggesting that episode onset is stochastic whereas episode termination occurs deterministically, when network excitability falls to a fixed level. This is true over a wide range of developmental stages and under blockade of glutamatergic or GABAergic/glycinergic synapses. We also demonstrate that during glutamatergic blockade the remaining part of the network becomes more excitable, compensating for the loss of glutamatergic synapses and allowing spontaneous activity to recover. This compensatory increase in the excitability of the remaining network reflects the progressive increase in synaptic efficacy that occurs in the absence of activity. Therefore, the mechanism responsible for the episodic nature of the activity automatically renders this activity robust to network disruptions. The results are presented using the framework of our computational model of spontaneous activity in the developing cord. Specifically, we show how they follow logically from a bistable network with a slow activity-dependent depression switching periodically between the active and inactive states.

Animals↗
PubMed2000

Modeling of spontaneous activity in developing spinal cord using activity-dependent depression in an excitatory network.

Spontaneous episodic activity is a general feature of developing neural networks. In the chick spinal cord, the activity comprises episodes of rhythmic discharge (duration 5-90 sec; cycle rate 0.1-2 Hz) that recur every 2-30 min. The activity does not depend on specialized connectivity or intrinsic bursting neurons and is generated by a network of functionally excitatory connections. Here, we develop an idealized, qualitative model of a homogeneous, excitatory recurrent network that could account for the multiple time-scale spontaneous activity in the embryonic chick spinal cord. We show that cycling can arise from the interplay between excitatory connectivity and fast synaptic depression. The slow episodic behavior is attributable to a slow activity-dependent network depression that is modeled either as a modulation of cellular excitability or as synaptic depression. Although the two descriptions share many features, the model with a slow synaptic depression accounts better for the experimental observations during blockade of excitatory synapses.

Animals↗
PubMed1999

NMDA-induced dendritic oscillations during a soma voltage clamp of chick spinal neurons.

An investigation of dendritic membrane properties was performed by whole-cell patch measurements of the biophysical properties of intact chick spinal neurons that are involved in rhythmogenesis. A whole-cell voltage clamp of the somatic membrane was used to block NMDA-induced voltage oscillations from the cell body, thus partially isolating the intrinsic oscillatory properties of dendritic membranes from those of the soma. An experimental approach was developed that takes into account the complexity of the dendritic tree in an environment as normal as possible, without the need for cell isolation or slice preparations. A computational study of the experimentally determined model showed that excitatory amino acid receptors on dendrites can dynamically control the electrotonic length of the dendrites through the activation of negative slope conductances. These experiments demonstrate the presence of NMDA receptors on the dendrites and that they induce intrinsic oscillations when the synaptic input from other cells is significantly reduced.

Animals↗
PubMed1999

Spontaneous network activity transiently depresses synaptic transmission in the embryonic chick spinal cord.

We examined the effects of spontaneous or evoked episodes of rhythmic activity on synaptic transmission in several spinal pathways of embryonic day 9-12 chick embryos. We compared the amplitude of synaptic potentials evoked by stimulation of the ventrolateral funiculus (VLF), the dorsal or ventral roots, before and after episodes of activity. With the exception of the short-latency responses evoked by dorsal root stimulation, the potentials were briefly potentiated and then reduced for several minutes after an episode of rhythmic activity. Their amplitude progressively recovered in the interval between successive episodes. The lack of post-episode depression in the short-latency component of the dorsal root evoked responses is probably attributable to the absence of firing in cut muscle afferents during an episode of activity. The post-episode depression of VLF-evoked potentials was mimicked by prolonged stimulation of the VLF, subthreshold for an episode of activity. By contrast, antidromically induced motoneuron firing and the accompanying calcium entry did not depress VLF-evoked potentials recorded from the stimulated ventral root. In addition, post-episode depression of VLF-evoked synaptic currents was observed in voltage-clamped spinal neurons. Collectively, these findings suggest that somatic postsynaptic activity and calcium entry are not required for the depression. We propose instead that the mechanism may involve a form of long-lasting activity-induced synaptic depression, possibly a combination of transmitter depletion and ligand-induced changes in the postsynaptic current accompanying transmitter release. This activity-dependent depression appears to be an important mechanism underlying the occurrence of spontaneous activity in developing spinal networks.

Animals↗
PubMed1998

Mechanisms of spontaneous activity in the developing spinal cord and their relevance to locomotion.

The isolated lumbosacral cord of the chick embryo generates spontaneous episodes of rhythmic activity. Muscle nerve recordings show that the discharge of sartorius (flexor) and femorotibialis (extensor) motoneurons alternates even though the motoneurons are depolarized simultaneously during each cycle. The alternation occurs because sartorius motoneuron firing is shunted or voltage-clamped by its synaptic drive at the time of peak femorotibialis discharge. Ablation experiments have identified a region dorsomedial to the lateral motor column that may be required for the alternation of sartorius and femorotibialis motoneurons. This region overlaps the location of interneurons activated by ventral root stimulation. Wholecell recordings from interneurons receiving short latency ventral root input indicate that they fire at an appropriate time to contribute to the cyclical pause in firing of sartorius motoneurons. Spontaneous activity was modeled by the interaction of three variables: network activity and two activity-dependent forms of network depression. A "slow" depression which regulates the occurrence of episodes and a "fast" depression that controls cycling during an episode. The model successfully predicts several aspects of spinal network behavior including spontaneous rhythmic activity and the recovery of network activity following blockade of excitatory synaptic transmission.

Animals↗
PubMed1998

Simulation and parameter estimation study of a simple neuronal model of rhythm generation: role of NMDA and non-NMDA receptors.

Simple neural network models of the Xenopus embryo swimming CPG, based on the one originally developed by Roberts and Tunstall (1990), were used to investigate the role of the voltage-dependent N-methyl-D-aspartate (NMDA) receptor channels, in conjunction with faster non-NMDA components of synaptic excitation, in rhythm generation. The voltage-dependent NMDA current "follows" the membrane potential, leading to a postinhibitory rebound that is more efficient than one without voltage dependency and allows neurons to fire more than one action potential per cycle. Furthermore, the model demonstrated limited rhythmic activity in the absence of synaptic inhibition, supporting the hypothesis that the NMDA channels provide a basic mechanism for rhythmicity. However, the rhythmic properties induced by the NMDA current were observed only when there was moderate activation of the non-NMDA synaptic channels, suggesting a modulatory role for this component. The simulations also show that the voltage dependency of the NMDA conductance, as well as the fast non-NMDA current, stabilizes the alternation pattern versus synchrony. To verify that these effects and their implications on the mechanism of swimming and transition to other types of activity take place in the real preparation, constraints on parameter values have to be specified. A method to estimate synaptic parameters was tested with generated data. It is shown that a global analysis, based on multiple iterations of the optimization process (Foster et al., 1993), gives a better understanding of the parameter subspace describing network activity than a standard fit with a sensitivity analysis for an individual solution.

Animals↗
PubMed1984

Late phase bronchial obstruction following nonimmunologic mast cell degranulation.

Immunologic degranulation of airway mast cells after antigen inhalation produces early and late airway obstructions in allergic sheep. In this study we determined whether nonimmunologic degranulation of airway mast cells by inhalation of compound 48/80 had similar effects. In five sheep, pulmonary flow resistance (RL), thoracic gas volume (Vtg), and arterial O2 tension (Pao2) were determined prior to and at predetermined times after inhalation of 48/80 aerosol. Immediately after challenge mean specific lung resistance (sRL = RL X Vtg) increased by 259% and mean Pao2 decreased by 29%. All values returned to normal by 3 h. By 5-h postchallenge sRL again increased significantly; this second increase in sRL (92% above base line) was maximal at 7 h and was accompanied by a 17% drop in Pao2. In these same sheep inhalation of Ascaris suum antigen produced comparable early changes in sRL, but the onset of the late response was somewhat delayed and more pronounced. In a second group of sheep (n = 5), pretreatment with the mast cell stabilizer cromolyn sodium prevented both early and late responses by compound 48/80. Pretreatment with the histamine H1-antagonist chlorpheniramine had no significant effect on either response, whereas pretreatment with FPL 55712, an antagonist of slow-reacting substance of anaphylaxis (SRS-A), slightly but not significantly attenuated the early response and completely prevented the late response. We conclude that, like immunologic stimuli, nonimmunologic mast cell degranulation produces early and late bronchial obstructions in allergic sheep; that these responses are mediator dependent; and that while histamine and SRS-A contribute to the early response, it is the early appearance of SRS-A which is an important prerequisite for the late response.

Airway Obstruction↗
PubMed1982

Survival of patients with cancer in a medical critical care unit.

The records of 40 patients with cancer and 684 patients without cancer admitted to a medical critical care unit were reviewed for the purpose of comparing survival. Patients with cancer had a higher mortality (55%, 22/40) than the patients without cancer (17%, 118/864). Patients with cancer and respiratory failure had a higher mortality (75%, 18/24) than patients without cancer but with respiratory failure (25%, 66/273) and a higher mortality than patients with cancer but without respiratory failure (25%, 4/16). In patients with cancer, the manifestation of respiratory failure as the adult respiratory distress syndrome (ARDS) was associated with a high mortality (86%, 12/14), which was not statistically higher than in patients with cancer with non-ARDS respiratory failure (60%, 6/10) or in patients without cancer with ARDS (65%, 28/43). Patients with cancer but without respiratory failure had a mortality of 25% (4/16). All eight patients with cancer admitted to the hospital because of life-threatening metabolic disturbances survived. In deciding whether to apply critical care techniques to a patient with cancer, the physician should consider the specific nature of the life-threatening illness.

Adult↗
PubMed1975

The effect of butaclamol and of other neuroleptic agents on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity.

The effects of the two enantiomers of butaclamol and of several neuroleptics on the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity was investigated. The (+) but not the (-) enantiomer of butaclamol reverses the apomorphine-elicited enzyme inhibition. (+) Butaclamol is more potent than the other tested neuroleptics. All the tested neuroleptics reverse the apomorphine-elicited enzyme inhibition but their relative potency differs. Using two criteria, namely the concentrations of neuroleptics required to reverse enzyme inhibition maximally or by 25%, the order of decreasing potency is as follows: (+) butaclamol, fluphenazine, haloperidol, pimozide, chlorpromazine. The results suggest that the reversal of apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity is a valid test model for screening antipsychotic drugs.

Animals↗
PubMedDate not supplied

Parameter estimation methods for single neuron models.

With the advancement in computer technology, it has become possible to fit complex models to neuronal data. In this work, we test how two methods can estimate parameters of simple neuron models (passive soma) to more complex ones (neuron with one dendritic cylinder and two active conductances). The first method uses classical voltage traces resulting from current pulses injection (time domain), while the second uses measures of the neuron's response to sinusoidal stimuli (frequency domain). Both methods estimate correctly the parameters in all cases studied. However, the time-domain method is slower and more prone to estimation errors in the cable parameters than the frequency-domain method. Because with noisy data the goodness of fit does not distinguish between different solutions, we suggest that running the estimation procedure a large number of times might help find a good solution and can provide information about the interactions between parameters. Also, because the formulation used for the model's response in the frequency domain is analytical, one can derive a local sensitivity analysis for each parameter. This analysis indicates how well a parameter is likely to be estimated and helps choose an optimal stimulation protocol. Finally, the tests suggest a strategy for fitting single-cell models using the two methods examined.

Animals↗
PubMedDate not supplied

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Dentistry↗