TY - JOUR AU - Li, Meng AU - Liu, Jun AU - Tsien, Joe Z. PY - 2016 M3 - Perspective TI - Theory of Connectivity: Nature and Nurture of Cell Assemblies and Cognitive Computation JO - Frontiers in Neural Circuits UR - https://www.frontiersin.org/articles/10.3389/fncir.2016.00034 VL - 10 SN - 1662-5110 N2 - Richard Semon and Donald Hebb are among the firsts to put forth the notion of cell assembly—a group of coherently or sequentially-activated neurons—to represent percept, memory, or concept. Despite the rekindled interest in this century-old idea, the concept of cell assembly still remains ill-defined and its operational principle is poorly understood. What is the size of a cell assembly? How should a cell assembly be organized? What is the computational logic underlying Hebbian cell assemblies? How might Nature vs. Nurture interact at the level of a cell assembly? In contrast to the widely assumed randomness within the mature but naïve cell assembly, the Theory of Connectivity postulates that the brain consists of the developmentally pre-programmed cell assemblies known as the functional connectivity motif (FCM). Principal cells within such FCM is organized by the power-of-two-based mathematical principle that guides the construction of specific-to-general combinatorial connectivity patterns in neuronal circuits, giving rise to a full range of specific features, various relational patterns, and generalized knowledge. This pre-configured canonical computation is predicted to be evolutionarily conserved across many circuits, ranging from these encoding memory engrams and imagination to decision-making and motor control. Although the power-of-two-based wiring and computational logic places a mathematical boundary on an individual’s cognitive capacity, the fullest intellectual potential can be brought about by optimized nature and nurture. This theory may also open up a new avenue to examining how genetic mutations and various drugs might impair or improve the computational logic of brain circuits. ER -