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

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.

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Journal
Nature Communications
Published
2026-09-14
DOI
https://doi.org/10.1038/s41467-026-77800-w
Primary Topic
Neuroscience and Neuropharmacology Research
Type
article
Field-Weighted Citation Impact
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article

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

Alessio Attardo, A.F. Ulivi, Rosa-Eva Huettl, Silvia Vieweg et al.
Nature Communications
Neuroscience and Neuropharmacology Research
article

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

Alessio Attardo, A.F. Ulivi, Rosa-Eva Huettl, Silvia Vieweg, David Kappel, Stefan Remy, Ali Özgür Argunşah, Bhargavi Murthy, Hannah Klimmt, Felix Kuhn
article en

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.

Nature CommunicationsVol. 17(1)
Bielefeld University (DE), University of Zurich (CH), German Center for Neurodegenerative Diseases (DE), Center for Behavioral Brain Sciences (DE), Max Planck Institute of Psychiatry (DE), Ludwig-Maximilians-Universität München (DE), Leibniz Institute for Neurobiology (DE)
Deutsche Forschungsgemeinschaft, Instituo Cajal, Leibniz-Gemeinschaft, European Regional Development Fund
Openalex Percentile: Top 17%
Neuroscience and Neuropharmacology Research
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