The amygdaloid complex: from morphology to neurodegeneration

Abstract The amygdaloid complex is one of the most structurally and functionally heterogeneous regions of the mammalian brain, acting as an integrative node between sensory, mnemonic and visceral systems. It comprises a set of subnuclei whose cytoarchitectural differentiation, neurochemical profiles and anatomical boundaries have been debated since the earliest descriptions. This heterogeneity is established during ontogenetic development, assembling progenitors from pallial and subpallial domains, and preoptic and hypothalamic territories, resulting in a highly connected network. Maturation is not complete at birth, the amygdala changes through childhood and adolescence, leaving a protracted window of environmental sensitivity. Single-nucleus RNA sequencing and spatial transcriptomics have added a molecular layer to this framework, resolving populations that no single marker separates, and set explicit limits on the resolution at which rodent-derived subdivisions can be transferred to the human amygdala. Together these levels of description provide a structural framework for understanding its functions, which include emotional regulation and conditioned fear, social and sexual behaviours, decision-making, reward and punishment processing, empathy and memory modulation. Cross-species comparison reveals further variation, particularly the expansion of the basolateral complex in primates and the redistribution of neurons towards the lateral nucleus in humans. In summary, the amygdala acts as a densely connected hub with a broad role not only in physiological and psychological health but also in disease states; indeed, the amygdala is affected early in several neurodegenerative disorders, and in some (notably limbic-predominant age-related TDP-43 encephalopathy and argyrophilic grain disease) it is among the first regions in which pathology is detected.