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Biomedical subjects

Stephen J Redman

Publications and source records attributed to Stephen J Redman.

4 recordsLinked to original sources
PubMed2003

Quantal analysis based on density estimation.

When direct measurements of the quantal parameters for a synapse cannot be made, these parameters can be extracted from an analysis of the fluctuations in the evoked response at that synapse. In this article, a decision tree is described in which the ability of the data to match simple models of quantal transmission is rigorously compared with its ability to fit progressively more complex models. The Wilks statistic is the basis for this comparison. The procedure commences with optimal transformation of peak amplitude measurements into a probability density function (PDF). It then examines this PDF against various models of transmission, commencing with a multi-modal but non-quantal distribution, then to a multi-modal distribution with quantal peak separation with and without quantal variability, and, finally, the constraints of uniform and non-uniform release probabilities are imposed. These procedures are illustrated by example. A comparison is made between the relative sensitivities of the Wilks statistic and the chi2 goodness-of-fit criteria in rejecting inappropriate models at all stages in these procedures.

Analysis of Variance↗
PubMed2003

Calcium dynamics, buffering, and buffer saturation in the boutons of dentate granule-cell axons in the hilus.

The axons of dentate gyrus granule cells form synapses in the hilus. Ca(2+) signaling was investigated in the boutons of these axons using confocal fluorescence imaging. Boutons were loaded with various concentrations of the Ca(2+) indicator Oregon Green BAPTA-1 by patch-clamping the cell bodies and allowing the dye to diffuse into the axon. Resting free [Ca(2+)] started at 74 nm, rose to approximately 1 microm immediately after an action potential, and then decayed to rest with a time constant of 43 msec (all extrapolated to a dye concentration of zero). Action potential-induced [Ca(2+)] rises were smaller in larger boutons, consistent with a size-independent Ca(2+) channel density of 45/microm(2). Action potential-induced [Ca(2+)] changes varied with dye concentration in a manner consistent with kappa(E) approximately 20 for the ratio of endogenous buffer-bound Ca(2+) to free Ca(2+). During trains of action potentials, [Ca(2+)] increments summed supralinearly by more than that expected from dye saturation. The amount of endogenous Ca(2+) buffering declined as [Ca(2+)] rose, and this saturation indicated a buffer with a dissociation constant of approximately 500 nm and a concentration of approximately 130 microm. This is similar to the dissociation constant of calbindin-D28K, a Ca(2+)-binding protein that is abundant in dentate granule cells. Thus, calbindin-D28K is a good candidate for the Ca(2+) buffer revealed by these experiments. The saturation of endogenous buffer can generate short-term facilitation by amplifying [Ca(2+)] changes during repetitive activity. Buffer saturation may also be relevant to the presynaptic induction of long-term potentiation at synapses formed by dentate granule cells.

Action Potentials↗
PubMed2002

Different calcium sources are narrowly tuned to the induction of different forms of LTP.

The essential role of calcium in the induction of long-term potentiation (LTP) has been well established. In particular, calcium influx via the N-methyl-D-aspartate (NMDA) receptor (NMDAR) is important for LTP induction in many pathways. However, the specific roles of other calcium sources in hippocampal LTP are less clear. The aim of the present study was to determine the appropriate conditions and extent to which non-NMDAR Ca(2+) sources contribute to the induction of different forms of LTP in area CA1 of hippocampal slices. Increasing numbers of theta-burst trains (1, 4, and 8 TBS) induced LTP of increasing magnitude and persistence. Inhibition of ryanodine receptors caused inhibition of weak LTP induced by 1 TBS, but had no effect on more robust forms of LTP. Inhibition of IP3 receptors inhibited moderate LTP induced by 4 TBS, but had no effect when 1 TBS or 8 TBS were used. Inhibition of L-type voltage-dependent Ca(2+) channels inhibited strong LTP induced by 8 TBS, but had no effect on weaker forms of LTP. These results show that different Ca(2+) sources have different thresholds for activation by TBS trains. Furthermore, each Ca(2+) source appears to be tuned to the induction of a different form of LTP. Such tuning could reflect an important link between different LTP induction and maintenance mechanisms.

Animals↗