AUTHOR=Vivien Juliette , El Azraoui Anass , Lheraux Cloé , Lanore Frederic , Aouizerate Bruno , Herry Cyril , Humeau Yann , Bienvenu Thomas C. M. 

TITLE=Axo-axonic cells in neuropsychiatric disorders: a systematic review

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=Volume 17 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2023.1212202

DOI=10.3389/fncel.2023.1212202

ISSN=1662-5102

ABSTRACT=Imbalance between excitation and inhibition in the cerebral cortex is one of the main theories in neuropsychiatric disorder pathophysiology. Cortical inhibition is finely regulated by a variety of highly specialized GABAergic interneuron types, which are thought to organize neural network activities. Among interneurons, axo-axonic cells are unique in making synapses with the axon initial segment of pyramidal neurons. Their potential key role in physiology is mirrored in disease. Indeed, alterations of axo-axonic cells have been implicated in disorders including epilepsy, schizophrenia and autism, in which they may have critical etiological importance. Despite the recognized therapeutic potential of restoring normal axo-axonic function, evidence for axo-axonic roles in disease has only been examined in opinion reviews. By performing a systematic review of axo-axonic cells deficits in epilepsy, schizophrenia and autism spectrum disorder, we outline convergent findings and discrepancies in the literature. Overall, the implication of axo-axonic cells in neuropsychiatric disorders might have been overstated. Additional work is needed to assess initial, mostly indirect, findings and to unravel how defects in axo-axonic cells translates to cortical dysregulation and, in turn, to pathology.