| dc.description.abstract | What underlies the extraordinary capacity of neurons to process information, form memories, and orchestrate complex behaviors? Over a century of research has established that proteins are the central functional molecules of the cell, yet translating this knowledge into an understanding of emergent neural phenomena and effective treatments for neurological disorders remains elusive. We argue that this paradox stems from studying proteins in isolation, overlooking how their function is fundamentally shaped by spatial context and interactions with DNA, RNA, other proteins, lipids, carbohydrates, and metabolites. This coordinated
molecular interplay, we posit, ultimately gives rise to the complex neural circuits and behaviors observed in higher organisms. Intriguingly, Alfred Binet foreshadowed this perspective as early
as 1889 when he suggested that even simple, single-celled organisms—lacking anatomically defined nervous systems—might harbor a "diffuse nervous system" of molecular interactions
within their cytoplasm enabling complex behaviors. However, the historical progression of neuroscience, largely dictated by available methodologies and oscillating between siloed reductionist molecular approaches and systems-level analyses, has not yet been able to fully capture this intricate molecular choreography underlying neural function. In this review, we examine how studying molecular species in isolation, while yielding important insights, has ultimately proven insufficient for understanding emergent neural functions. We propose that recent technological advances in expansion microscopy, molecular anchoring, machine learning-enabled
protein detection, and cryo-fixation now make it possible to map molecular networks in their native context. This integrative approach promises to illuminate the molecular "language" of the brain, shedding light on how collective interactions among biomolecules
give rise to neuronal emergent abilities—and guide future therapeutic innovations. | |
