Dopaminergic neurons regulate and organize numerous important behavioral processes including motor activity.Consistently,manipulation of brain dopamine concentrations changes animal activity levels.Dopamine is synthes...Dopaminergic neurons regulate and organize numerous important behavioral processes including motor activity.Consistently,manipulation of brain dopamine concentrations changes animal activity levels.Dopamine is synthesized by several neuronal populations in the brain.This study was carried out to directly test whether selective activation of dopamine neurons in the midbrain induces hyperactivity.A pharmacogenetic approach was used to activate midbrain dopamine neurons,and behavioral assays were conducted to determine the effects on mouse activity levels.Transgenic expression of the evolved hM3Dq receptor was achieved by infusing Creinducible AAV viral vectors into the midbrain of DATCre mice.Neurons were excited by injecting the hM3Dq ligand clozapine-N-oxide（CNO）.Mouse locomotor activity was measured in an open field.The results showed that CNO selectively activated midbrain dopaminergic neurons and induced hyperactivity in a dose-dependent manner,supporting the idea that these neurons play an important role in regulating motor activity.展开更多
基金supported by the National Basic Research Development Program (973 Program) of the Ministry of Science and Technology of China (2010CB833902)
文摘Dopaminergic neurons regulate and organize numerous important behavioral processes including motor activity.Consistently,manipulation of brain dopamine concentrations changes animal activity levels.Dopamine is synthesized by several neuronal populations in the brain.This study was carried out to directly test whether selective activation of dopamine neurons in the midbrain induces hyperactivity.A pharmacogenetic approach was used to activate midbrain dopamine neurons,and behavioral assays were conducted to determine the effects on mouse activity levels.Transgenic expression of the evolved hM3Dq receptor was achieved by infusing Creinducible AAV viral vectors into the midbrain of DATCre mice.Neurons were excited by injecting the hM3Dq ligand clozapine-N-oxide（CNO）.Mouse locomotor activity was measured in an open field.The results showed that CNO selectively activated midbrain dopaminergic neurons and induced hyperactivity in a dose-dependent manner,supporting the idea that these neurons play an important role in regulating motor activity.
