Presence and function of synapses on axons in an evolutionarily conserved neuronal population in mammals

• Applicant: Professor Dr. Felix Felmy
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 571265140

Axons are the main output compartments of neurons responsible for transmitting information playing a central role for neuronal communication and enabling complex processes such as movement, cognition, and hearing. Synaptic input along the axonal compartment can locally modulate neuronal excitability, facilitate or suppress action potential generation, and finely tune the timing and fidelity of signal propagation. While such mechanisms are increasingly recognized in some brain regions, their existence and functional relevance in auditory pathways remain largely unexplored. Yet in these pathways timing and precision of action potentials is vital. This project aims to investigate the structure and function of axonal synapses in the medial nucleus of the trapezoid body (MNTB), a key brainstem structure in the auditory system essential for precise binaural processing and sound localization. While somatic synaptic integration in the MNTB has been extensively studied, the organization and role of additional axonal synaptic inputs are not known. Our preliminary data suggest the presence of such axonal-synapses on the MNTB neuron output-compartment. We will use high-resolution, serial block face scanning electron microscopy and expansion microscopy to prove the presence and quantify the spatial distribution of axonal synapses and determine the structure of the axonal compartment in the MNTB. To assess the functional relevance of these synapses, we will build a computational model based on experimentally measured axonal geometry and synapse distribution. This model will simulate how local synaptic input at the axon modulates action potential initiation and propagation. These predictions will be tested using in vitro electrophysiology, where local neurotransmitter application at the axon will be used to probe the effects of axonal input on spike timing and fidelity. In a comparative approach, we will investigate axonal synapses in both mice and Etruscan shrews, species providing an ideal model system to explore how brain size and behavior shaped neuronal circuits. Although species-specific differences in the input-output function of MNTB neurons reflect ecological adaptations, the structure and overall circuit function of these neurons is conserved. Thus, studying axonal synaptic organization and function in the MNTB allows us to identify species-specific adaptations while minimizing confounding variables in respect to the inter-species comparison. Together, this project combines structural, functional and computational methods to provide a comprehensive analysis of axonal synapses in an ultra-precise auditory circuit. Moreover, the comparative approach allows conclusions beyond auditory processing, offering broader implications for understanding sensory system adaptations across species.

• DFG Programme: Research Grants