The "Where" and "Who" in brain science : probing brain networks with local perturbations

Abstract

In a reductionistic approach to biology, the two important questions of "necessity" and "sufficiency" have been tremendously important for scientific progress. For example, to show the role of a particular gene, both knock-out mutants ("necessity") and rescue mutants ("sufficiency") need to be considered. These concepts, however, fail in combinatorial network situations. When emergent brain properties arise from the interaction of multiple brain areas, and redundant paths lead to resilience, then none of these areas can be identified as either "necessary" or "sufficient." Here, we use a relatively small-scale network—the glomerular odor-activity map-as a model for redundant combinatorial coding mechanisms. In particular, we use local interference with the functioning network with inhibitory and excitatory neuropharmacological injections to probe the resulting network perturbations. In vivo calcium imaging affords us with access to much of the network activity in real time. We observed, for example, that these local perturbations can generate physiological changes in distant places of the brain. This has important implications for our understanding of neural networks, in particular about the question of "where" a particular capacity—e.g., consciousness—is localized in the brain, and "who" (which cell) is involved. A related important question is "how" a function emerges, i.e., which neural networks are underlying this function? This issue can be addressed using combined functional and anatomical study of the network.