Neurosteroid-induced enhancement of short-term facilitation involves a component downstream from presynaptic calcium in hippocampal slices.
We used Magnesium Green AM to measure Ca(2+) transients in Schaffer collateral presynaptic terminals simultaneously with postsynaptic field potentials (fEPSPs) to investigate the mechanism of neurosteroid enhancement of short-term synaptic facilitation. Measurement of [Ca(2+)](i), isolated to presynaptic events, using the fluorescence ratio (DeltaF/F(0)) demonstrated that at a constant stimulus intensity there was no change in the excitability of presynaptic fibres between paired stimuli or between ACSF and 1 mum pregnenolone sulphate (PREGS). Paired-pulse facilitation (PPF) was correlated with residual Ca(2+) ([Ca(2+)](res)), and there was an additional increase in the integralDeltaF/F(0) for the [Ca(2+)](res)-subtracted response to the second of paired stimuli, resulting primarily from a slowing of the decay time constant. In addition to the role of presynaptic [Ca(2+)](res) in PPF, we observed a decrease in EC(50) and a greater maximum for Hill function fits to fEPSP versus DeltaF/F(0) during the second of paired responses. The enhancement of fEPSP PPF by PREGS did not result from an increase of DeltaF/F(0). The data presented here support a PREGS-induced increase in presynaptic glutamate release from the second, but not the first, of a pair of stimuli for a given presynaptic [Ca(2+)] because: (a) there is actually a decrease in the integralDeltaF/F(0) of the [Ca(2+)](res)-subtracted second response over that seen in ACSF; (b) PREGS causes no change in presynaptic Ca(2+) buffering; and (c) there is a decrease in EC(50) and an increase of y(max) in the Hill function fits to DeltaF/F(0) versus fEPSP data. We hypothesize that PREGS enhances short-term facilitation by acting on the Ca(2+)-dependent vesicle release machinery and that this mechanism plays a role in the cognitive effects of this sulphated neurosteroid.
Schiess
Adrian R B
AR
Department of Neurosciences, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA.
Scullin
Chessa S
CS
Partridge
L Donald
LD
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005456:Fluorescent Dyes; D005998:Glycine / Q000031:analogs & derivatives; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011284:Pregnenolone / Q000494:pharmacology*; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D014966:Xanthenes
D005456:Fluorescent Dyes; D018377:Neurotransmitter Agents; D014966:Xanthenes; C018370:pregnenolone sulfate; C453498:magnesium green; D011284:Pregnenolone; D002118:Calcium; D005998:Glycine