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bioRxiv · 10.1101/2025.03.04.641429

Learning reorganizes dendritic and stabilizes axonal initial segment inhibitory synapses in CA1 pyramidal neurons

Klimmt, H.·Kappel, D.·Ulivi, A. F.·Argunsah, A. O.·Murthy, B.·Somatakis, S.·Huettl, R. E.·Remy, S.·Attardo, A.
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Abstract

Structural synaptic plasticity underlies the changes in brain connectivity required for learning and memory. Inhibitory synapses (INS) target all subcellular domains of excitatory pyramidal neurons (PNs), including dendrites, somata and axon initial segments (AIS). These subcellular domains have distinct molecular, structural and physiological profiles which underlie their functions. How structural plasticity of INS supports these functions as well as emerging properties such as memory is largely unknown. To tackle these questions we tracked INS on dendrites, somata and AIS of PNs in the dorsal hippocampal CA1 area of mice over two weeks. Size and temporal dynamics of INS showed a strong compartmentalization and dendritic INS were less dynamic than dendritic spines. Trace fear conditioning led to reorganization of dendritic INS and to stabilization of AIS INS but had a minimal effect on dendritic spines. Finally, mathematical modelling allowed us to probe the mechanisms underlying stabilization of INS upon learning.

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Klimmt, H., Kappel, D., Ulivi, A. F., Argunsah, A. O., Murthy, B., Somatakis, S., Huettl, R. E., Remy, S., Attardo, A.. 2025-03-05. Learning reorganizes dendritic and stabilizes axonal initial segment inhibitory synapses in CA1 pyramidal neurons. https://doi.org/10.1101/2025.03.04.641429

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