A Principle for Describing and Verifying Brain Mechanisms Using Ongoing Activity

Not even the most informed scientist can setup a theory that takes all brain signals into account. A neuron not only receives neuronal short range and long range input from all over the brain but a neuron also receives input from the extracellular space, astrocytes and vasculature. Given this complexity, how does one describe and verify a typical brain mechanism in vivo? Common to most described mechanisms is that one focuses on how one specific input signal gives rise to the activity in a population of neurons. This can be an input from a brain area, a population of neurons or a specific cell type. All remaining inputs originating from all over the brain are lumped together into one background input. The division into two inputs is attractive since it can be used to quantify the relative importance of either input. Here we have chosen to extract the specific and the background input by means of recording and inhibiting the specific input. We summarize what it takes to estimate the two inputs on a single trial level. The inhibition should not only be strong but also fast and the specific input measurement has to be tailor-made to the inhibition. In essence, we suggest ways to control electrophysiological experiments in vivo. By applying those controls it may become possible to describe and verify many brain mechanisms, and it may also allow the study of the integration of spontaneous and ongoing activity, which in turn governs cognition and behavior.