Molecular regulators of brain function: a new view.

A working hypothesis is proposed based on two mutually dependent concepts: neurons may be functionally regulated not only by presently known neurotransmitters but by many kinds of informational substances. Known informational substances are considered in categories corresponding to major regulators of the central nervous system, including transmitters, peptides, hormones, "factors" and various proteins. Many new informational substances are being discovered by the application of DNA technology. Alongside neuronal circuitry that forms the basis for conventional neuroanatomy and neurophysiology, and that operates through conventional synaptic junctions, is a system here called parasynaptic, i.e. in "parallel with" synapse-linked circuitry. In the parasynaptic system, informational substances reach specific target cell receptors by diffusion from release points through extracellular fluids. The parasynaptic system has the same degree of selectivity as synaptic circuitry but possesses, in addition, a domain of versatility and plasticity lacking in "hardwired" circuitry; the latter is, however, also influenced by highly potent informational substances in the ambient extracellular fluid.