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Biomedical subjects

G F Ayala

Publications and source records attributed to G F Ayala.

At least 19 recordsLinked to original sources

MtDNA control region and RFLP data for Sicily and France.

The forensic application of mtDNA typing requires large databases which are regionally well defined. To further this aim, we have typed mtDNA in a sample of 111 French and 106 Sicilians. The French were typed for both hypervariable segments (HVR1 and HVR2) of the mtDNA control region, whereas the Sicilians were only typed for HVR1, but in addition for the coding region RFLP markers for mtDNA groups H, I, J, K, L, M, T, U, V and X. In both samples, the predominant sequence type by far was the Cambridge reference sequence. Comparing HVR1 sequences, we found that the French sample was twice as diverse as the Sicilian sample as measured by sequence matches. A further set of sequence match comparisons including the French, Sicilian, and the published British mtDNA samples, demonstrate that sequence matching probabilities within samples differ by less than a factor of 2 from the matching probabilities between samples.

Complementarity Determining Regions↗

Quantitative modeling of perception and production of time intervals.

The accurate perception/production of durations in the seconds and minutes range is important in a number of everyday activities, but the lack of direct experimental evidence on the neural circuits that could be involved has precluded the detailed elucidation of the underlying physiological mechanisms. We show, using a basic biophysical model of a timekeeping system and experimental data on time intervals produced or estimated under different conditions, that experimental values, variability, and distributions can be quantitatively explained in terms of a background synaptic activity such as that generated by attention. The model provides a plausible neural substrate for encoding time intervals, and the findings suggest how it may interplay at the single neuron level with the attentional system, to elaborate a subjective representation of the elapsing time.

Humans↗

Possible roles of retrograde messengers on LTP, LTD, and associative memory.

There are still no clear biophysical models for Associative Long-Term Potentiation (LTP) and Depression (LTD) in the hippocampus, where two populations of synapses targeted to the same receptive field are involved. Here we propose a model that allows an interpretation of the experiments in terms of the molecular processes that may be involved in associative memory. The model suggests that retrograde messengers could have a critical role in the induction and maintenance of associative LTP and LTD, by controlling the coupling between the two populations of synapses.

Electric Stimulation↗

A model for long-term potentiation and depression.

A computational model of long-term potentiation (LTP) and long-term depression (LTD) in the hippocampus is presented. The model assumes the existence of retrograde signals, is in good agreement with several experimental data on LTP, LTD, and their pharmacological manipulations, and shows how a simple kinetic scheme can capture the essential characteristics of the processes involved in LTP and LTD. We propose that LTP and LTD could be two different but conceptually similar processes, induced by the same class of retrograde signals, and maintained by two distinct mechanisms. An interpretation of a number of experiments in terms of the molecular processes involved in LTP and LTD induction and maintenance, and the roles of a retrograde signal are presented and discussed.

Animals↗

Transputer-based parallel system for acquisition and on-line analysis of single-fiber electromyographic signals.

We describe a transputer-based system suitable for accurate measurements of single-fiber electromyographic jitter. It consists of a conventional electromyograph, a home-made interface and a commercially available transputer-based board installed within a PC/AT compatible. Taking advantage of the concurrent operation of two transputer modules, the system features simultaneous data acquisition and statistical signal processing: while data are acquired and analyzed, a real-time visualization of the signal latency and its variability is provided. In the present configuration, the system can acquire and analyze up to 40,000 consecutive action potentials, which can be grouped into up to eight sets at different stimulation rates programmable up to 16 Hz. Since the determination of the electromyographic signal latency relies on least-squares smoothing and interpolation of the acquired data rather than on amplitude-threshold triggering, a low value (0.7 microsecond) of so called technical jitter is achieved. Computing power and memory can be easily extended by addition of transputer-based modules. Typical results of data acquisition and on-line analysis are reported.

Diagnosis, Computer-Assisted↗

Cellular mechanisms of epilepsy: a status report.

The cellular phenomena underlying focal epilepsy are currently understood in the context of contemporary concepts of cellular and synaptic function. Interictal discharges appear to be due to a combination of synaptic events and intrinsic currents, the exact proportion of which in any given neuron may vary according to the anatomic and functional substrate involved in the epileptic discharge and the epileptogenic agent used in a given model. The transition to seizure appears to be due to simultaneous increments in excitatory influences and decrements in inhibitory processes--both related to frequency-dependent neuronal events. A variety of specific hypotheses have been proposed to account for the increased excitability that occurs during epileptiform activity. Although each of the proposed mechanisms is likely to contribute significantly to the epileptic process, no single hypothesis provides an exclusive unifying framework within which all kinds of focal epilepsy can be understood. The spread of epileptic activity throughout the brain, the development of primary generalized epilepsy, the existence of "gating" mechanisms in specific anatomic locations, and the extrapolation of hypotheses derived from simple models of focal epilepsy to explain more complex forms of human epilepsy, all are not yet fully understood.

Action Potentials↗

A late increase in potassium conductance follows synaptic stimulation of granule neurons of the dentate gyrus.

In response to orthodromic stimulation, granule neurons of the dentate gyrus of the rat hippocampal slice display a late hyperpolarization (LH) with properties which clearly distinguish it from the conventional gamma-aminobutyric ac id (GABA)-mediated chloride (Cl) dependent inhibitory postsynaptic potential (IPSP). The LH is not reduced by antagonists of GABA-mediated Cl conductances such as picrotoxin, and it is probably dependent on increased potassium conductance rather than in increased Cl conductance. The LH can be elicited by orthodromic stimulation which does not elicit a burst of action potentials and, in fact, the LH has been observed following stimulation which did not produce a depolarization detectable at the resting membrane potential. It is suggested that the increased potassium conductance of the LH may be calcium-dependent, or it may be directly elicited by a neurotransmitter.

Animals↗

Effects of phenytoin on pyramidal neurons of the rat hippocampus.

The effects of phenytoin (35 micrograms/ml) on membrane properties and inhibitory postsynaptic potential (IPSPs) in CA1 and CA3 pyramidal neurons of the in vitro rat hippocampus were examined. No significant change was observed on input resistance or resting membrane potential. Action potential amplitude, overshoot, rate of rise and rate of decay were decreased. IPSP conductance increase and reversal potential, evoked in CA3 cells through mossy fiber stimulation and in CA1 cells through recurrent and Schaffer's collateral stimulation, were unaffected.

Animals↗

Biphasic response of hippocampal pyramidal neurons to GABA.

GABA released either iontophoretically or synaptically near pyramidal neurons in the CA1 region of the rat hippocampal slice could produce a biphasic response: a hyperpolarization followed by a depolarization. The depolarizing component elicited by either method was accompanied by an increased membrane conductance, and a reduction in neuronal discharge. The depolarization was reversed at a potential which was less negative than the resting membrane potential; it was blocked by antagonists of GABA action such as picrotoxin; it was sensitive to manipulation of extracellular chloride concentration; and it persisted in the presence of concentrations of cobalt or manganese which were sufficient to block evoked synaptic activity. Iontophoresis of GABA near the apical dendrites elicited an initial depolarization rather than an initial hyperpolarization, suggesting a dendritic origin for the depolarizing component. Together, these results suggest that GABA can produce, in the same neuron, both hyperpolarizing and depolarizing responses which depend at least in part upon changes in chloride conductances.

Animals↗

The mechanism of action of diphenylhydantoin or invertebrate neurons. I. Effects on basic membrane properties.

The effect of diphenylhydantoin (DPH) has been studied on certain membrane properties of the crayfish stretch receptor neuron (SRN) and of neurons in the abdominal and buccal ganglia of Aplysia. DPH decreases the amplitude of post-tetanic hyperpolarization of the SRN, which is thought to be an expression of the electrogenic pump, and does not antagonize the effect of ouabain on this activity. DPH decreases the membrane resistance of all the different types of neurons studied, with little or no change in the resting membrane potential. It decreases the overshoot of the action potential in some of the neurons studied and prolongs the falling phase and the undershoot in other neurons. DPH also decreases repetitive firing. These effects have also been observed at different external concentrations of potassium. It is concluded that DPH, in the different preparations studied, does not have any effect on or decreases the electrogenic pump, but produces changes in other membrane properties which are consistent with its anticonvulsant action.

Action Potentials↗

The mechanism of action of diphenylhydantoin on invertebrate neurons. II. Effects on synaptic mechanisms.

The effect of diphenylhydantoin (DPH) on certain synapses of neurons in the abdominal ganglion of Aplysia and on the gamma-aminobutyric acid (GABA) mediated inhibitory synapse of the crayfish stretch receptor neuron (SRN) has been studied. DPH decreases the amplitude of the excitatory postsynaptic potential, but is ineffective on the "short" ACh mediated, Cl- dependent, inhibitory postsynaptic potential (IPSP) in Aplysia. However, it facilitates the "long" ACh mediated, K+ dependent, IPSP, in this same group of neurons. DHP has a profound effect on the GABA mediated, Cl- dependent, inhibitory synapse of the SRN. The time course of the IPSP is prolonged up to 10 times control values, due to an increased and prolonged postsynaptic conductance. Similar results have been obtained in the SRN with iontophoretic application of GABA. This selective effect of DPH on synaptic mechanisms, especially in view of the role of GABA and ACh as putative transmitters in the mammalian nervous system, may play an important role for the anticonvulsant action of DPH.

Acetylcholine↗

The influences of phenytoin on the fundamental electrical properties of simple neural systems.

The effects of phenytoin on some neurophysiological properties of simple neuronal systems are reviewed. From all the available data phenytoin decreases or has no effect on post-tetanic hyperpolarization, which is interpreted as an expression of the electrogenic pump. Although in some neurons the membrane conductance is increased, the resting membrane potential is minimally affected. The effect on the action potential varies with different preparations and with different neurons of the same ganglion. If an effect is present, the overshoot is decreased or the falling phase is prolonged, or both. Post-synaptic potentials are also affected by phenytoin. EPSPs are decreased in size, while the chloride-dependent, GABA-mediated IPSPs of the crayfish stretch receptor are prolonged. No effect was seen on chloride-dependent, ACh-mediated IPSPs in the abdominal ganglion of the Aplysia. Finally, phenytoin arrests endogenous or pharmacologically induced bursting. Most of the described effects are consistent with the antiarrhythmic and antiepileptic properties of the drug.

Action Potentials↗