Short-term synaptic plasticity

We use a variety of electro-physiological, optical imaging, molecular, and analytic approaches to study short-term synaptic plasticity at levels ranging from molecular to computational, in synapses of the central nervous system.

Background: Traditionally, synapses have been thought to faithfully relay signals encoded by presynaptic spike trains. But, recently it has become clear that synapses also play a central role in processing the information that is transmitted because their strength changes rapidly and dramatically during episodes of the type of repetitive use common during normal brain function, i.e. in the frequency domain. These transient changes are known as short-term synaptic plasticity, or STP.  Presently, we do not have a coherent framework for understanding either the underlying cell biological principles, or the role this phenomenon plays in brain function.

Because nearly all synapses exhibit substantial amounts of STP during routine use, understanding STP will be key for understanding how brains work - i.e. "cracking the neural code" - which is one of the main intellectual challenges of our time.  Current work also has important medical relevance because dysregulation of STP has been implicated as one of the earliest events in the etiology and pathophysiology of neurological diseases ranging from epilepsy to Parkinson´s and Alzheimer´s disease – which makes sense for a process that plays a central role in biological computation.

Current work: work in the laboratory is focused on short-term synaptic plasticity from four perspectives:

1. Biophysics/Electrophysiology: dissection of the underlying kinetic elements
2. Molecular Biology: finding molecular elements modulate STP
3. Computational Biology/ Optical Imaging: understanding the physiological role
4. Technological Development: a high throughput fluorescence based assay for drug screening is being developed which will allow unbiased searches for reagents that uniquely modulate single kinetic elements of synaptic function, with the ultimate goal of treating several important neurological disorders.