"Mechanistic understanding of neuronal function: towards a physical theory of the brain"

The brain is a highly complex system with multiple spatial and temporal scales, and deeply understanding it will require a physical theory tying together different levels of description, from the molecular to the behavioral.  While a working understanding of superconductivity does not require the standard model, one understands how the standard model fits in with superconductivity, predicting the particles whose properties allow for it.  The same cannot be said for neuroscience, and indeed, the way in which microscopic components influence macroscopic properties is an open question in the physics of neuroscience and biology more generally.   

On one end, systems neuroscience has proposed a wide and diverse set of functions that neurons must perform in order to achieve emergent network properties.  On the other side, biologists and biophysicists have characterized the microscopic properties of many molecular components of neurons:  ion channels, membranes, transporters and the cytoskeleton, among others.  In ion channels, enormous progress has been made characterizing input-output relationships, macroscopic expression profiles and even subcellular localization.  At somewhat larger scales, the nanoscale structure of the neuronal cytoskeleton has recently been probed, showing completely unforeseen, highly regular structure.  While these advances are profound, they are at present primarily descriptive, and do not often connect to our understanding of the functional properties of neurons and circuits.

There are cases where progress has been made in connecting disparate levels of description. In the 50s, Hodgkin and Huxley showed that a simple biophysical model in which the neuronal membrane’s conductance to specific ions is voltage sensitive could lead to a diverse array of collective behaviors including the action potential.  Their efforts have shaped neuroscience at all levels.  At the biophysical level, voltage-dependent sodium and potassium channels implementing their theory were later discovered, while at the systems level, measuring action potential spikes often suffices to quantify behavior.

Despite these successes, our understanding of the biophysics underlying most neural processes remains in its infancy.  Therefore I am focusing my research agenda on developing a quantitative understanding of systems level phenomenon and tying it with the underlying neuronal biophysics. Please check my research page for more details.