Synapse organizers as molecular codes for synaptic plasticity

Abstract

Synapse organizing proteins are multifaceted molecules that coordinate the complex processes of brain development and plasticity at the level of individual synapses. Their importance is demonstrated by the major brain disorders that emerge when their function is compromised. The mechanisms whereby the various families of organizers govern synapses are diverse, but converge on the structure, function, and plasticity of synapses. Therefore, synapse organizers regulate how synapses adapt to ongoing activity, a process central for determining the developmental trajectory of the brain and critical to all forms of cognition. Here, we explore how synapse organizers set the conditions for synaptic plasticity and the associated molecular events, which eventually link to behavioral features of neurodevelopmental and neuropsychiatric disorders. We also propose central questions on how synapse organizers influence network function through integrating nanoscale and circuit-level organization of the brain.

Keywords: MAM domain-containing GPI anchor; leucine-rich-repeat transmembrane neuronal proteins; long-term depression; long-term potentiation; neurexin; neurodevelopment; neuroligin; neuropsychiatric disorders; synapse organizing proteins; synaptic adhesion molecules.