Heterogeneous plasticity of amygdala interneurons in associative learning and extinction

Favila, N.; Capece Marsico, J.; Escribano, B.; Pacheco, C. M.; Bitterman, Y.; Gründemann, J.; Lüthi, A.; Krabbe, S.

doi:10.1101/2024.09.29.612271

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bioRxiv · 10.1101/2024.09.29.612271

Heterogeneous plasticity of amygdala interneurons in associative learning and extinction

Favila, N.·Capece Marsico, J.·Escribano, B.·Pacheco, C. M.·Bitterman, Y.·Gründemann, J.·Lüthi, A.·Krabbe, S.

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Abstract

Neural circuits undergo experience-dependent plasticity to form long-lasting memories. Excitatory projection neurons are considered to be the primary neuronal substrate for memory acquisition and storage. However, inhibitory interneurons control the activity of projection neurons in a in a spatially and temporally precise manner, yet their contribution to memory acquisition, storage and expression remains poorly understood. Here, we employ a miniature microscope imaging approach to monitor the activity of large amygdala interneuron populations in freely moving mice during fear learning and extinction at the single cell level. We find that amygdala interneurons display mixed-selectivity and show complex plastic responses at both the ensemble and single neuron level across the acquisition, expression and extinction of aversive memories. In contrast to bidirectional single cell plasticity across distinct fear states, learning-induced changes at the population level occur transiently during conditioning and do not consolidate across days. Examining molecular interneuron subpopulations revealed that disinhibitory vasoactive intestinal peptide (VIP) expressing cells are predominantly activated by high fear states. In contrast, somatostatin (SST) interneurons display a preference for safety cues and thereby suppress excitatory neuron responsiveness. However, responses of individual neurons within the SST and VIP populations are non-uniform, indicating the presence of functional subtypes within classical molecularly-defined interneuron populations. Taken together, we identify complex neuronal plasticity within amygdala interneuron ensembles that goes beyond a passive processing function, suggesting a critical role of inhibitory microcircuit elements for memory selectivity and stability.

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Favila, N., Capece Marsico, J., Escribano, B., Pacheco, C. M., Bitterman, Y., Gründemann, J., Lüthi, A., Krabbe, S.. 2024-09-29. Heterogeneous plasticity of amygdala interneurons in associative learning and extinction. https://doi.org/10.1101/2024.09.29.612271

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