The Molecular Architecture of Somatic Spines of the Lateral Septum

The lateral septum is a key subcortical structure and has been implicated in kinship memory. Across species, the ability to recognise relatives is conserved and is reflected in stable, lifelong memories. The molecular mechanisms underlying kinship memory remain elusive. Here we investigate the synaptic architecture of septal circuits and focus on somatic spines, an apparent synaptic specialisation of this mainly GABAergic structure. We uncover the molecular organisation of septal somatic spines found in the lateral septum using a combination of unbiased imaging methods and confocal microscopy. We used classical label-free methods such as transmission electron microscopy and Golgi stainings and established new culturing methods for dissociated and organotypic septal slice cultures 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. While smaller than dendritic spines, somatic spines exhibited distinct features, frequently containing secretory organelles such as phagophores and endosomes, but often lack a spine apparatus and ribosomes. Our findings offer insights on the molecular architecture of septal somatic spines and establish a basis for further investigations on the somatic spines of the lateral septum and their role in kinship memory. Significance statementSpine synapses represent stable synaptic connections that allow neurons to chemically communicate with each other. Although known for decades, the unusual spine synapses found directly on neuronal cell bodies in the lateral septum have not been characterised in detail. Using traditional, unbiased approaches such as electron microscopy and Golgi stainings, we replicate the initial findings. Additionally, using fluorescent microscopy of dissociated and organotypic septal cultures, we characterise the development and composition of septal somatic spines. We find that they are excitatory, contain membranous organelles and develop independently of extra-septal input. We thus describe model systems suitable for the investigation of somatospiny neurons of the lateral septum.