The present invention provides a sensitive system for measuring the physiological response of an in-vitro cell culture to an environmental parameter. An electrical property of the cell culture is measured as a control signal, and a parameter of a stimulus is adjusted in real time to maintain the control signal at a specified value as the environment of the cell culture is altered, for example, pharmacologically. Artifact reduction and real-time control methods are two key aspects of preferred embodiments of the invention, and enable highly accurate determination of pulse parameters which elicit a desired response. Both aspects must be highly robust to the natural variations inherent in a biological system. This system is beneficial for studying the effects of environmental alterations because extremely small changes in the physiological response can be measured over time, revealing the magnitude and time-dependence of the impact of these alterations on the cell culture.