Researchers will examine the dynamics of intracellular signaling that give rise to the formation of synapses, junctions connecting one brain cell to another to facilitate communication and plasticity.
One key component in the development of synapses between two brain cells is activation (phosphorylation) of amino acids called “tyrosine kinases.” Overall, several families of tyrosine kinases are involved in synaptic events. These events include formation of “dendritic spines” (tiny mushroom-like protrusions that receive neurotransmitters from across the synapse), synaptic maturation, and brain plasticity. Precise activation of tyrosine kinase receptors located on cells helps to guide development of synaptic connections, while their over-activation is implicated in developmental disorders and in diseases such as cancers. The investigators hypothesize that the spatial and temporal dynamics of tyrosine kinase signaling, and regulation of these, help control the outcomes of these synaptic functions.
They will test this hypothesis using molecular imaging with fluorescent phosphorylation reporters, which enable them to visualize and quantify increases and decreases in tyrosine kinase signaling within laboratory animal neurons in tissue cultures. First, they will image this signaling as cells’ dendritic spines explore their environment and generate synaptic connections. Then, the investigators will image events involved in neuronal plasticity, to see how signaling flows between or along pathways. These experiments are anticipated to define the signaling events that underlie cells’ dynamic establishment and loss of synaptic connections.