Out of the single-neuron straitjacket: assembling cells to unveil dynamic coding

Understanding how billions of neurons communicate and coordinate their activity is a central pursuit of neuroscience. The concept of cell assemblies emerges as a fundamental unit of neural organization, embodying the intricate interplay of individual neurons within the complex web of the brain's circuits. The notion of cell assemblies has evolved alongside our understanding of neural dynamics and information processing, transcending epochs since its inception. Over the decades, this concept has undergone significant refinement and expansion, shaped by the contributions of a wide range of influential scientists and researchers from different fields of study. This thesis will explore the process that led to its formalization up to the present day. I will introduce three studies that I carried out during these years as a Ph.D. student, which are closely related to this topic and to the many practical applications of this theory that has so strongly influenced the thinking of generations of neuroscientists. In the first study, following up on a debate that has been going on for almost a century, I will compare the activity of individual neurons with the coordinated activity at the cell assembly level, demonstrating, as was theorized in the early twentieth century in psychological Gestalt theory, that the whole is something other than the sum of its parts. Starting from my mathematical background, where these two concepts coincide perfectly, I approached this question with caution, but slowly it has become completely part of my way of thinking. I am not suggesting that one approach is necessarily better than the other, only that they are different. Cell assembly analysis provides an alternative perspective on neuronal coding by shifting the focus from the traditional single-neuron approach to highlight the dynamic role of individual neurons within collective coding mechanisms. The second study will address the issue of stable or dynamic encoding over time using a population-level approach. This concept will be combined with the one discussed above to examine how it leads to increased or decreased reconfiguration at the network and cell assembly level. In the last study, I will explore a further application of the theory by analyzing a dataset spanning multiple brain areas, selecting cross-regional assemblies, and attempting to relate this functional inter-area coordination to the underlying cognitive dynamics by analyzing specific types of coordination motifs. Overall, the evolution of cell assembly theory reflects a rich history of interdisciplinary collaboration and empirical inquiry, with each successive generation of researchers building on the insights of their predecessors to deepen our understanding of the neural basis of cognition and behavior. From Lorente De No' and Donald Hebb's foundational work to modern advances in systems neuroscience and neurotechnology, the cell assembly theory continues to inspire research and innovation in the quest to unravel the mysteries of the brain.