The Molecular Architecture of Somatic Spines of the Lateral Septum

ABSTRACT The lateral septum is a key subcortical structure and has been implicated in social memory. One aspect of social memory, the ability to recognize relatives, is conserved across vertebrate species and reflected in stable, lifelong memories. Synapses are considered to be the smallest unit of memory storage. Excitatory synapses are typically found on dendritic spines, whereas inhibitory synapses are mostly located on the dendritic shaft. Here, we investigate the synaptic architecture of unusual somatic spines, an apparent synaptic specialization of septal GABAergic neurons. We uncover the formation and molecular organization of septal somatic spines found in the lateral septum in in vivo and in vitro model systems using various microscopy approaches. We use classical label‐free methods such as transmission electron microscopy and Golgi stainings and established new culturing methods for dissociated and organotypic septal slices that were kept in culture over multiple weeks. We describe the presence, morphology, ultrastructure, and molecular composition of excitatory somatic spines across multiple developmental stages in various model systems. We propose that the ability to develop such spines is an intrinsic feature of somatospiny neurons that does not depend on extra‐septal connectivity. While smaller than dendritic spines, somatic spines exhibited distinct features, frequently containing secretory organelles such as autophagosomes, multivesicular bodies, and endosomes, but often lacking a spine apparatus and ribosomes. Our findings offer insights into the molecular architecture of septal somatic spines and establish a basis for further investigations into the somatic spines of the lateral septum.