25 In TCS, a weak electric field is generated by exogenous current application to modulate neuronal BMS-907351 activity (discussed below). Yet, the most challenging aspect of the question about the possible role of endogenous electric fields beyond a simple epiphenomenon remained unaddressed: what are the effects of weak activity-dependent electric fields (ie, “feedback”) such as the ones that occur in vivo during synchronized activity? selleck chemicals feedback Inhibitors,research,lifescience,medical electric fields Feedback refers to any system that receives input that is not predefined (ie, “feedforward”), but rather depends on the

behavior of the system itself (Figure 2). Control engineering is a highly effective branch of engineering that develops algorithms for feedback control of complex systems such as airplanes and chemical plants. In essence, these algorithms process real-time measurements such as velocity or temperature and decide what the best input (“control signal”) is to achieve a given behavior Inhibitors,research,lifescience,medical of the system, such as smoothly landing an airplane or inducing a specific chemical reaction in a production

plant. Such feedback control Inhibitors,research,lifescience,medical systems are also omnipresent in biology as feedback represents a fundamental approach to maintain homeostasis (here, broadly defined). Regulation of insulin to control blood sugar is one of the numerous examples of such feedback regulation in biological systems. Returning to electric fields generated by neuronal activity, the question arises whether the “feedback” electric fields have similar effects as the “feedforward” electric fields used in the studies discussed above. In other words, does an endogenous Inhibitors,research,lifescience,medical electric field that tracks the endogenous network activity (ie, that occurs in vivo in the intact brain) also enhance these dynamics?

Studying feedback systems is an experimentally difficult task Inhibitors,research,lifescience,medical that is often achieved by a so-called “separation of time scales” approach where the system is essentially studied without the feedback signal and a range of feedforward signals are Carfilzomib individually evaluated. The behavior of the feedback system is then reconstructed by forming a composite of the feedforward responses of the system. For example, extracellular potassium concentration in the extracellular space fluctuates with neuronal activity, but the potassium concentration changes on a much slower time scale than the neuronal activity due to buffering and reuptake mechanisms.26 However, in the case of endogenous electric fields, this approach is not appropriate since the electric field varies on the same time scale as neuronal activity. As a result of these technical and conceptual difficulties, the possible role of endogenous electric fields in shaping neuronal network activity has remained unclear.