Presynaptic terminals are simultaneously dynamic and stable structures.  They can persist over a period of months while behaving in a highly plastic manner over a time scale of seconds to hours.  This plasticity is believed to underlie important brain functions such as learning and memory.  The molecules that give rise to neurotransmitter secretion must therefore solve this apparent contradiction of stability and plasticity.   

We are currently studying the mechanisms underlying recruitment and retention of a variety of presynaptic molecules using photoactivatable GFP fusion proteins.  We image synapses in vivo and quantify the kinetics of protein exchange between synapses for a given molecule.   By examining changes in these protein dynamics in a variety of synaptic mutants, we hope to learn how synapses maintain and modulate their molecular identity.

In C. elegans, both Acetylcholine (ACh) and GABA are released in the nerve cord and mediate fast neuromuscular excitation and inhibition during locomotion.  These neurotransmitters activate a muscarinic receptor (GAR-2) and the GABA_B receptor dimer (GBB-1/2) that detect synaptically released ACh and GABA, respectively.  These receptors are expressed on motor neurons and possibly interneurons controlling locomotion.

We are exploring ways of detecting the molecular events that underlie GPCR modulation of the motor neurons as well as rewiring the modulatory circuitry of the worm by missexpressing GPCRs within the nervous system.