The molecular motor kif5b mediates the function of dopamine D2 receptors and is necessary for the cross talk between direct and indirect nigrostriatal pathway in locomotion

ALLOATTI, MATÍAS; TRINIDAD M.M. SAEZ; FALZONE, TOMÁS L.; CROMBERG, LUCAS ENEAS; FERRARI, JUAN

Buenos Aires

Congreso; FALAN Congress 2016; 2016

FALAN

The coordinated stimulation of the direct and indirect striatal pathways from nigral dopaminergic (DAergic) neurons allow the initiation and the persistence of a locomotor response. Nigral and striatal neurons depend on a complex transport system for the continuous neurotransmitter release and a correct DA (D1-5) receptor presentation, respectively. To determine whether transport defects impair the direct or indirect nigrostriatal pathway, we analyzed locomotion in mice with conditional deletion of the molecular motor kif5b. Neuronal Kif5b deletion (Kif5b/Nestin-CRE) induced hipolocomotion while enhanced movement initiation and impaired coordination, without DAergic degeneration.However, kif5b deletion from DAergic neurons showed no locomotor deficits suggesting that DA vesicle transport and release is not affected by kif5b deletion in nigral neurons. To test whether Kif5b/Nestin-CRE defects involved the direct or indirect striatal neurons we analyzed their locomotor response using D1 antagonists (SCH 23390) or D2 agonist (quinpirole). Reduction of movement episodes were induced under amphetamine stimulation, while quinpirolewas unable to restore movement initiation in Kif5b/Nestin-CRE compared with control suggesting that proper physiological function of D2-like receptors is impaired. HPLC to measure DA levels and release will be performed to confirm our results. We suggest that D2 depends on kif5b-mediated transport for the direct-indirect pathway crosstalk.