Array tomography of synapses known to have undergone plasticity
One problem with trying to associate activity-dependent forms of synaptic plasticity, forms such as LTP and LTD, with anatomical changes in synapses, is that it is difficult to find and identify those particular synapses that underwent the plasticity in question. By inducing plasticity in only the synapses made between a pair of neurons, by making simultaneous whole cell recordings on a single pre- and a single postsynaptic neuron, and filling those neurons with traceable markers, we can find the points of contact between those two neurons using array tomography. Subsequent immunostaining of the arrays allows us to study particular proteins within those identified synapses and the location of those proteins. By correlating that proteomic information with the plasticity state of the synapse, we can discover how protein movements contribute to the plasticity.
Array tomography of myelination in the cortex
Myelin is best known for its role in increasing the conduction velocity and metabolic efficiency of long-range excitatory axons. We recently discovered that a significant proportion of cortical gray matter myelin covers the axons of inhibitory interneurons, and in particular parvalbumin basket cells. Using array tomography, as well as a novel combination of electrophysology and array tomography, we are aiming to characterize the myelination of PV basket cells and explore its functional significance.
Mammalian synapses are highly diverse in their structure and molecular composition. As part of the Open Synaptome Project, which includes teams from the Allen Institute, Johns Hopkins, UNC Chapel Hill, Duke, UC Davis and UC San Francisco, we are participating in the development of a high-throughput pipeline based on array tomography, aimed to measure, analyze and model synapse populations in both mouse and human brains.