Biomedical subjects

T B Woolf

Publications and source records attributed to T B Woolf.

22 records · Page 2Linked to original sources

PubMed1994

A molecular dynamics study of gating in dioxolane-linked gramicidin A channels.

The gating transition of the RR and SS dioxolane ring-linked gramicidin A channels were studied with molecular dynamics simulations using a detailed atomic model. It was found that the probable reaction path, describing the transition of the ring from the exterior to the interior of the channel where it blocked the permeation pathway, involved several steps including the isomerization of the transpeptide plane dihedral angle of Val1. Reaction coordinates along this pathway were defined, and the transition rates between the stable conformers were calculated. It was found, in good accord with experimental observations, that the calculated blocking rate for the RR-linked channel was 280/s with a mean blocking time of 0.04 ms, whereas such blocking did not occur in the case of the SS-linked channel. An important observation is that the resulting lifetime for the blocked state of the RR-linked channel was in good accord with the experimental observations only when the calculations were performed in the presence of a potassium ion inside the channel.

Dioxolanes↗

PubMed1991

Serial reconstructions of granule cell spines in the mammalian olfactory bulb.

The morphology of olfactory bulb granule cell spines and their dendrodendritic synaptic relations with mitral and tufted cell dendrites were examined using serial electron micrographs and 3D computer reconstructions. Most granule cell spines were pedunculated with large elliptical heads and necks (stems) longer than those described for exclusively postsynaptic spines elsewhere in the nervous system. The spines typically contained a mitochondrion, which most likely reflects the metabolic requirements of the presynaptic functions of these spines. In several cases multiple spine heads were observed connected to the parent dendritic trunk via a common neck. In addition, dendritic varicosities making synaptic connections were noted. In the data set sampled, all of the reconstructions supported the hypothesis of divergence of granule cell connectivity: in no instance was a granule cell found to contact repeatedly the same mitral or tufted cell dendrite. Examination of the topological organization of reciprocal dendrodendritic synaptic connections with mitral/tufted cell dendrites revealed parallel rows of spine heads on mitral/tufted secondary dendrites separated by intervening zones of several microns in which no synaptic appositions were found. The results provide evidence regarding rules of connectivity underlying the function of local circuits in mediating lateral inhibition in the external plexiform layer of the olfactory bulb.

Animals↗

PubMed1991

Local information processing in dendritic trees: subsets of spines in granule cells of the mammalian olfactory bulb.

The anaxonic granule cell of the olfactory bulb is believed to inhibit mitral and tufted cells through reciprocal dendrodendritic synapses. However, little is known about the detailed input-output properties of the granule cell. This study explores the functional properties of granule cells by using detailed reconstructions of Golgi-impregnated granule cells as the basis for computational models. Three Golgi-impregnated granule cells from the olfactory bulbs of C57BL/6j mice were selected for detailed analysis. Measurements were made of the diameter and length of all spine heads, spine necks, and dendritic branches. These measurements formed the basis of a compartmental model of each cell in which simulations of the spread of synaptic potentials within the dendritic tree were performed with SABER (Analogy, Inc.), a circuit analysis program. The results show that the degree of spread of synaptic potentials can define functionally related subsets of spines within the dendritic tree. The size of these subsets varies with the anatomical location of the input spine, the magnitude of the input, the time course of the input, the size of the spine neck resistance, and the activity of other spines. The data indicate that the functional organization of granule cell dendritic arbors is more complex than previously thought: between the level of the individual spine and the entire dendritic tree are several levels of subsets of spines that can mediate discrete localized inhibition onto subsets of mitral or tufted cell secondary dendrites within the external plexiform layer of the olfactory bulb.

Animals↗

PubMed1990

Neuron simulations with SABER.

Computational models can provide critical tests of hypotheses of neuronal function. These models are essential for dealing with the complications of time- and voltage-dependent (active) ionic conductances. Commercial circuit analysis programs have been useful tools for this work. We report our experience modelling biophysically realistic membrane properties with SABER (Analogy, Inc.), a new general purpose simulator. SABER allows construction of models with arbitrary membrane properties. This is a major advantage over similar programs (e.g. SPICE), which are limited to a predefined library of electronic components. The empirically determined equations that describe rate constants, ionic conductances, currents, and concentration shifts can be translated directly into model elements ('templates') written in C-like code. We describe the development of SABER models that simulate a synapse and an action potential.

Action Potentials↗