Wherefore art thou, homeo(stasis)? Functional diversity in homeostatic synaptic plasticity

Abstract

Homeostatic plasticity has emerged as a fundamental regulatory principle that strives to maintain neuronal activity within optimal ranges by altering diverse aspects of neuronal function. Adaptation to network activity is often viewed as an essential negative feedback restraint that prevents runaway excitation or inhibition. However, the precise importance of these homeostatic functions is often theoretical rather than empirically derived. Moreover, a remarkable multiplicity of homeostatic adaptations has been observed. To clarify these issues, it may prove useful to ask: why do homeostatic mechanisms exist, what advantages do these adaptive responses confer on a given cell population, and why are there so many seemingly divergent effects? Here, we approach these questions by applying the principles of control theory to homeostatic synaptic plasticity of mammalian neurons and suggest that the varied responses observed may represent distinct functional classes of control mechanisms directed toward disparate physiological goals.

Figure 1

Closed-loop control in homeostatic regulation. In closed-loop control systems, observed activity values (a) are compared to a desired set point (yellow star) (b) and deviations are registered as errors (c). The homeostatic response program is calculated and initiated in response to the error signal (d). Many control strategies are possible, including proportional-integral (PI) control (left) and bang-bang control (right). PI control: PI controllers compute a compensatory response as a function of the properties of the error, namely, the proportional (orange, magnitude at t = 0 indicated with arrow) and integral (purple, cumulative error over time) components of the deviation. A variation of this regulation, the proportional-integral-derivative (PID) controller, also incorporates a derivative component that detects the rate of change of the deviation (green bar in activity trace, D = k _D dE(t)/dt). The initiated response is therefore tailored to the immediate degree of deviation from the set point (proportional), the cumulative magnitude of the deviation (integral), and the rate of change of the deviation (derivative). Bang-bang control: Bang-bang control consists of set compensatory responses which are initiated once a threshold is crossed (blue lines) and halted once the activity value returns to the acceptable range of values.