Formation, stabilization, and dynamic modulation of GABAergic inhibitory synapses in the central nervous system

In the central nervous system (CNS), the chemical synapse is the major site of communication between neurons (nerve cells). There are two main types of synapses in the CNS: excitatory glutamate synapses and inhibitory gamma-aminobutyric acid (GABA) synapses. Dysfunction of GABA synapses has been identified in disorders such as autism, schizophrenia, and depression. GABA synapses are also the main targets for drugs to treat epilepsy and anxiety. The protein neuroligin is a molecule that directs a neuron to form a synapse at the place where it comes in contact with another neuron. A specific type of neuroligin, Neuroligin-2, builds GABA synapses. However, little is known about why and how Neuroligin-2 is specific for building GABA synapses. Frederick Dobie was previously funded by MSFHR for his research in protein transport in neurons. He is now studying proteins involved in synaptogenesis (the process of building a synapse). To better understand how GABA synapses are formed, he is looking at regions of Neuroligin-2 that are important for this function. He is also studying how GABA synapses can change over time, responding to the specific needs of the neuron to fit into a fully-functioning brain. He is watching the growth and maturation of synapses over a period of several days, observing in real-time the strikingly dynamic appearance, disappearance, and movement of synapses. By understanding the biology underlying GABA synapses, Dobie hopes his work will ultimately lead to the advancement of therapies for a wide range of debilitating developmental, neurological, and psychiatric disorders.