Sci. STKE, 1 July 2003
SYNAPTIC TRANSMISSION Maximizing Your Minis
Sharma and Vijayaraghavan investigated the modulation of neurotransmitter release from quiescent hippocampal neurons and discovered that calcium entering through presynaptic nicotinic acetylcholine receptors (nAChRs) led to bursts of glutamate release that were sufficient to drive the postsynaptic cell to threshold. Resting neurons spontaneously release the contents of individual synaptic vesicles at random intervals. The ensuing miniature postsynaptic potentials, which correspond to individual quanta of the postsynaptic response, are too small to affect firing in the postsynaptic cell, and their physiological function has remained obscure (see Preview by Zucker). Sharma and Vijayaraghavan recorded miniature excitatory postsynaptic currents (mEPSCs) from voltage-clamped CA3 pyramidal cells in rat hippocampal slices before, during, and after local application of nicotine. Nicotine increased the fraction of large mEPSCs in a manner consistent with the concerted release of multiple quanta and stimulated the production of high-frequency bursts of mEPSCs. Pharmacological analysis in combination with manipulation of the extracellular calcium concentration indicated that this increase in mEPSC amplitude and frequency depended on release of calcium from intracellular stores secondary to calcium influx through presynaptic nAChRs. When voltage clamp was released, glutamate released in response to nicotine application initiated bursts of action potentials in the postsynaptic cells. Thus, calcium influx through presynaptic nAChRs appears to provide a mechanism whereby impulses can be generated in the postsynaptic cell independent of the firing of the presynaptic neuron.
G. Sharma, S. Vijayaraghavan, Modulation of presynaptic store calcium induces release of glutamate and postsynaptic firing. Neuron 38, 929-939 (2003). [Online Journal]
R. S. Zucker, Can a synaptic signal arise from noise? Neuron 38, 845-846 (2003). [Online Journal]
Citation: Maximizing Your Minis. Sci. STKE 2003, tw246 (2003).
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882