Exciting inhibition: Local regulation of synapse formation and plasticity

Abstract

The brain consist of brain cells. These brain cells are connected through long processes and use these processes to send signals to each other. These connections are continuously changing when we process and store information. But how are these connections formed, and what rules do they follow when they change? The point where the process of two brain cells connect is called a synapse. An average brain cell receives thousands of synapses. Most of these synapses stimulate the brain cell. Some synapses can however inhibit the brain cell, thereby acting as “traffic controllers” guiding the signal processing within brain cells. For signals to be processed properly, a good coordination between stimulation and inhibition is required. In this thesis we study how this coordination is regulated within individual brain cells. Synapses can get stronger or weaker, but can also be formed and removed. These changes affect the coordination between stimulation and inhibition. We discovered that strengthening a few stimulating synapses on a single brain cell can trigger the formation of a new inhibitory synapse. We found that this process is regulated by a group of signaling molecules called endocannabinoids. We now have a better understanding how changes in brain connections are coordinated to maintain a balance between stimulation and inhibition. This is important because such coordinating processes seem to be disturbed in disorders such as epilepsy, schizophrenia and autism.