The Synaptomic Theory of Behavior and Brain Disease.

Abstract

The purpose of this article is to outline a new molecular and synaptic theory of behavior called the "synaptomic theory," named because it is centered on the synaptome-the complement of synapses in the brain. Synaptomic theory posits that synapses are structures of high molecular complexity and vast diversity that are observable in maps of the brain and that these synaptome maps are fundamental to behavior. Synaptome maps are a means of writing or storing information that can be retrieved by the patterns of activity that stimulate synapses. Synaptome maps have the capacity to store large amounts of information, including multiple representations within the same map. The dynamic properties of synapses allow synaptome maps to store dynamic sequences of representations that could serve to program behavioral sequences. Synaptome maps are genetically programmed and experience-dependent, thereby storing innate and learned behaviors, respectively. Although learning occurs by modification of the synapse proteome, it does not require long-term potentiation (LTP) of synaptic weight or growth of new synapses, and the theory predicts that LTP modulates information recall. The spatial architecture of synaptome maps arise from an underlying molecular hierarchy linking the genome to the supramolecular assembly of proteins into complexes and supercomplexes. This molecular hierarchy can explain how genome evolution results in the behavioral repertoire of the organism. Mutations disrupting this molecular hierarchy change the architecture of synaptome maps, potentially accounting for the behavioral phenotypes associated with neurological and psychiatric disorders.