Cortical regulation of subcortical dopamine systems and its possible relevance to schizophrenia.

A unique model of DA system regulation is presented, in which tonic steady-state DA levels in the ECF act to down-regulate the response of the system to pulsatile DA released by DA cell action potential generation. This type of regulation is similar in many respects to the phenomenon proposed to mediate the action of norepinephrine on target neurons; i.e., an increase in the "signal-to-noise" ratio as measured by postsynaptic cell firing (Freedman et al., 1977; Woodward et al., 1979). However, in this model the signal and the noise are neurochemical rather than electrophysiological. Furthermore, the "noise" (tonic DA in the ECF) actually down-regulates the "signal" (phasic DA release) directly, and thereby provides a "signal" of its own that affects the system over a longer time-course. Therefore, the difference between signal and noise may also depend on the time frame under which such determinations are made.