Pinceau organization in the cerebellum requires distinct functions of neurofascin in Purkinje and basket neurons during postnatal development

ED Buttermore, C Piochon, ML Wallace… - Journal of …, 2012 - Soc Neuroscience
Journal of Neuroscience, 2012Soc Neuroscience
Basket axon collaterals synapse onto the Purkinje soma/axon initial segment (AIS) area to
form specialized structures, the pinceau, which are critical for normal cerebellar function.
Mechanistic details of how the pinceau become organized during cerebellar development
are poorly understood. Loss of cytoskeletal adaptor protein Ankyrin G (AnkG) results in
mislocalization of the cell adhesion molecule Neurofascin (Nfasc) at the Purkinje AIS and
abnormal organization of the pinceau. Loss of Nfasc in adult Purkinje neurons leads to slow …
Basket axon collaterals synapse onto the Purkinje soma/axon initial segment (AIS) area to form specialized structures, the pinceau, which are critical for normal cerebellar function. Mechanistic details of how the pinceau become organized during cerebellar development are poorly understood. Loss of cytoskeletal adaptor protein Ankyrin G (AnkG) results in mislocalization of the cell adhesion molecule Neurofascin (Nfasc) at the Purkinje AIS and abnormal organization of the pinceau. Loss of Nfasc in adult Purkinje neurons leads to slow disorganization of the Purkinje AIS and pinceau morphology. Here, we used mouse conditional knock-out techniques to show that selective loss of Nfasc, specifically in Purkinje neurons during early development, prevented maturation of the AIS and resulted in loss of Purkinje neuron spontaneous activity and pinceau disorganization. Loss of Nfasc in both Purkinje and basket neurons caused abnormal basket axon collateral branching and targeting to Purkinje soma/AIS, leading to extensive pinceau disorganization, Purkinje neuron degeneration, and severe ataxia. Our studies reveal that the Purkinje Nfasc is required for AIS maturation and for maintaining stable contacts between basket axon terminals and the Purkinje AIS during pinceau organization, while the basket neuron Nfasc in combination with Purkinje Nfasc is required for proper basket axon collateral outgrowth and targeting to Purkinje soma/AIS. Thus, cerebellar pinceau organization requires coordinated mechanisms involving specific Nfasc functions in both Purkinje and basket neurons.
Soc Neuroscience