Non-linear regulation of synaptic transmission at individual synapses in the CNS

30 June 2010

Andrew Giessel
Sabatini Lab
Department of Neurobiology
Harvard Medical School


Excitatory synapses on mammalian principal neurons are typically formed onto dendritic spines, which consist of a bulbous head separated from the parent dendrite by a thin neck. These small structures (~1 micron in diameter) contain many ion channels, GPCRs, and other proteins which might shape the kinetics and amplitude of synaptic responses. We used a combination of two-photon imaging, two-photon photolysis of a caged version of the neurotransmitter glutamate, and deconvolution analysis of Ca transients to show that the specialized morphology of the spine neck interacts with voltage- and calcium-activated ion channels to shape the time-course of calcium influx during synaptic stimulation. Furthermore, we have shown that the proteins involved can be modulated by a secondary neurotransmitter system, via Gq-coupled cholinergic GPCRs. These results have importance in understanding the important role of neuronal morphology in synaptic transmission, as well as the mechanism of action of acetylecholine in the CNS.

virtual cell events