Neuronal transmission depends on the intrinsic ability of neurons to receive multiple synaptic inputs at different subcellular locations and integrate them into a response output. The integration process relies on neurotransmitter-receptor-mediated activation of a complex network of intracellular pathways. Advances in live microscopy techniques have allowed us to quantitatively visualize in real time signaling reactions in specific locations within the neuron. These types of studies have provided strong evidence of the inhomogeneous nature of spatial intracellular signaling. The Neves Laboratory is interested in understanding how these inhomogeneities in signaling events (called signaling microdomains) contribute to signal specificity in neuronal transmission.

To understand such complex processes across multiple levels of organization our approach is to integrate experiments with a quantitative framework. On the experimental side, we use FRET-based, real-time imaging approaches in intact living neurons to study the spatio-temporal dynamics of signaling. The increasing complexity of intracellular signaling requires us to combine FRET imaging with differential equation-based computational modeling to provide insight into the mechanisms that underlie specificity of signaling. These models have proven to be powerful, predictive tools that have revealed many non-intuitive features in neuronal signaling.

For more information, please visit the Neves Laboratory website.