Final Report Summary - SYNAPSECODE (Uncovering the role of new synaptic adhesion molecules in encoding synaptic connectivity in the brain)
The network of neurons in our brain encodes our thoughts, memories, and personalities. Neurons are precisely connected via specialized contacts called synapses, which mediate information transfer between neurons. Perturbations in synaptic connectivity are thought to underlie many brain disorders, such as autism, schizophrenia, and Alzheimer’s disease. Understanding how the many different types of synaptic contacts are formed and maintained is therefore important. However, the molecules and mechanisms involved are not well understood. In the SynapseCode project, we have studied the role of synaptic adhesion molecules in the development of precise synaptic connectivity. Synaptic adhesion molecules are key players in connectivity, because they physically connect neurons with each other and also regulate synaptic function, important for information transfer. We investigated the hypothesis that different types of synapses each have their own combinations of adhesion molecules that specify the specific properties of that synapse, forming a ‘synaptic adhesion code’. In our work, we have identified novel adhesion molecules that specify synaptic connectivity in different regions of the brain; mapped the diversity of synaptic adhesion molecules at different types of synapses onto the same neuron, and determined how these adhesion molecules regulate the formation, structure and function of specific synapses in vivo. We further identified a new sorting mechanism by which neurons control the abundance of adhesion molecules at synapses, and developed a new way to look into the composition of adhesion molecules at a specific synapse. Taken together, our work has generated new insights into the mechanisms that give rise to the formation and maintenance of precisely connected neural networks. Ultimately, these insights will guide the development of new strategies for the treatment of brain disorders.