TY - JOUR
T1 - Pinceau organization in the cerebellum requires distinct functions of neurofascin in purkinje and basket neurons during postnatal development
AU - Buttermore, Elizabeth D.
AU - Piochon, Claire
AU - Wallace, Michael L.
AU - Philpot, Benjamin D.
AU - Hansel, Christian
AU - Bhat, Manzoor A.
PY - 2012/4/4
Y1 - 2012/4/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84859361784&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84859361784&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.5602-11.2012
DO - 10.1523/JNEUROSCI.5602-11.2012
M3 - Article
C2 - 22492029
AN - SCOPUS:84859361784
SN - 0270-6474
VL - 32
SP - 4724
EP - 4742
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 14
ER -