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.