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bioRxiv · 10.1101/2024.11.08.622673

Ccp1 depletion disrupts network integration of hippocampal parvalbumin interneurons

Le Bail, R.·Lakaye, B.·Espuny Camacho, I.·Engel, D.·Silva, C.·Nguyen, L.
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Abstract

Post-translational modifications (PTMs) of microtubules (MTs) endow them with specific properties that are essential for key cellular functions, such as axonal transport. Polyglutamylation, a PTM that accumulates in long-lived MTs, has been linked to neurodegeneration in the cerebellum when in excess. While hyperglutamylation of MTs leads to neurodegeneration and disrupts the function of specific neuronal subtypes like Purkinje cells, cortical neurons, and hippocampal excitatory neurons, little is known about its impact on inhibitory interneurons and their functional integration into local networks. In this study, we generated a conditional knockout mouse model to deplete cytosolic carboxypeptidase 1 (Ccp1) in GABAergic neurons, a key MT deglutamylase expressed by hippocampal interneurons. Our findings reveal that the loss of Ccp1 has a profound effect on hippocampal parvalbumin (PV)-expressing interneurons, impairing their axonal transport and reducing their perisomatic inhibition of pyramidal cells (PCs) in the CA2 region of the hippocampus. Research TopicsMolecular Neuroscience, Cell Biology HighlightsO_LIDifferent subtypes of hippocampal interneurons express unique sets of (de)glutamylases and show varying levels of protein posttranslational glutamylation. C_LIO_LIParvalbumin interneurons become hyperglutamylated when Ccp1 activity is lost. C_LIO_LIThe loss of Ccp1 disrupts axonal transport in interneurons and is associated with decreased perisomatic inhibition of hippocampal pyramidal cells in the CA2 region. C_LI

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Le Bail, R., Lakaye, B., Espuny Camacho, I., Engel, D., Silva, C., Nguyen, L.. 2024-11-08. Ccp1 depletion disrupts network integration of hippocampal parvalbumin interneurons. https://doi.org/10.1101/2024.11.08.622673

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