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

Sep 2026 · Nature Communications · Vol 17 · 0 citations · 113 references
Medicine

TL;DR

Using repeated brain imaging, the authors find that inhibitory synapses change at different rates across neuronal subcellular compartments in mouse CA1.

Abstract

Structural synaptic plasticity underlies the changes in brain connectivity required for learning and memory. Inhibitory synapses target all subcellular domains of excitatory pyramidal neurons, including dendrites, somata and axon initial segments. These subcellular domains have distinct molecular, structural and physiological profiles which underlie their functions. How structural plasticity of inhibitory synapses supports these functions as well as emerging properties such as memory is largely unknown. To tackle these questions we tracked inhibitory synapses on basal dendrites, somata and axon initial segments of pyramidal neurons in the dorsal hippocampal CA1 area of mice over two weeks. Size and temporal dynamics of inhibitory synapses showed a strong compartmentalization. Trace fear conditioning led to reorganization of dendritic and to stabilization of axon initial segments’ inhibitory synapses. Finally, mathematical modelling allowed us to probe the mechanisms underlying stabilization of inhibitory synapses upon learning. Using repeated brain imaging, the authors find that inhibitory synapses change at different rates across neuronal subcellular compartments in mouse CA1. Fear learning reorganizes dendritic connections but stabilizes those at the axon initial segment, which may aid memory recall.

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