Figure 1.
Numerous influences converge on principal neurons leading to emergent properties. This is an idealized diagram of a principal neuron in a specific nucleus within a neuronal network in the brain of an awake, behaving organism that illustrates many of the influences that affect this “class” of neurons (N) in this nucleus. The neurons possess certain specific intrinsic properties (Φ), such as the propensity to exhibit burst firing or pacemaker activity. These cells also possess specific receptors (#) (metabotropic or ionotropic) onto which descending projections release a specific neuroactive substance. The neurons also possess ligand-gated receptors (V) (e.g., glutamate) (which have specific receptor subunits) onto which interneurons synaptically release a specific neuroactive substance. Projection neurons across the midline for bilaterally connected structures releasea neuroactive substance ø, which binds to its specific receptors on contralateral neurons. The principal neurons also possess the property of pH sensitivity (W). Ascending input from neuronsin nuclei in the network also release a neuroactive substance (¤), which binds to its specific receptors. The neurons possess voltage-gated ion channels (X) (e.g., K+ channels) at which local ions can act. The neurons receive input from local glial cells, which release a neuroactive substance (Y) (e.g., adenosine) that acts on specific receptors for this substance. Endogenous (Endo) neuroactive agents (Z) carried via volume transmission from nearby (spillover) or distant sites via the extracellular fluid and cerebrospinal fluid to the neurons also affect the properties of these neurons. An example would be extrasynaptic GABAA receptors that respond to the low levels of “ambient” GABA in the extracellular fluid. Finally, when an exogenous agent, such asa CNS drug or centrally acting toxin, is administered it is released via the brain blood vessels among other vectors to exert its effects on the emergent property of these principal cells to exert its effect on network function. The therapeutic effect of many CNS drugs is postulated to be mediated by a selective action on the principal cells in a specific nucleus in the neuronal network for the disorder to produce the desired effect. This selectivity is seen primarily when therapeutic doses are given. In addition, electrical, magnetic, or optogenetic neurostimulation can modulate the network and affect the emergent property. The summation of all these influences determines whether the emergent property is expressed and the actual nature of that property and its relative sensitivity in that group of neurons. This emergent property is postulated to be expressed uniquely in this network nucleus and causes this class of neurons to respond with unique sensitivityto a specific exogenous substance. Note, those influences can also be modified by brain state changes (such as sleep), whichcan significantly alter the emergent property, based on changesin milieu of the principal neuron as well as external stimulation. (Modified from Faingold 2014b, with permission.)