Two far-reaching theoretical approaches, namely “Neuro-semeiotics” (NS) and “Free-energy Minimization” (FEM), have been recently proposed as frames within which to put forward heuristic hypotheses on integrative brain actions. In the present paper these two theoretical approaches are briefly discussed in the perspective of a recent model of brain architecture and information handling based on what we suggest calling Jacob’s tinkering principle, whereby “to create is to recombine!”. The NS and FEM theoretical approaches will be discussed from the perspective both of the Roamer-Type Volume Transmission (especially exosome-mediated) of intercellular communication and of the impact of receptor oligomers and Receptor-Receptor Interactions (RRIs) on signal recognition/decoding processes. In particular, the Bio-semeiotics concept of “adaptor” will be used to analyze RRIs as an important feature of NS. Furthermore, the concept of phenotypic plasticity of cells will be introduced in view of the demonstration of the possible transfer of receptors (i.e., adaptors) into a computational network via exosomes (see also Appendix). Thus, Jacob’s tinkering principle will be proposed as a theoretical basis for some learning processes both at the network level (Turing-like type of machine) and at the molecular level as a consequence of both the plastic changes in the adaptors caused by the allosteric interactions in the receptor oligomers and the intercellular transfer of receptors. Finally, on the basis of NS and FEM theories, a unified perspective for integrative brain actions will be proposed.