Figure 8.

Ligands in the EGF family in circulation can penetrate the blood-brain barrier (BBB) during early development and act on the soma and terminals of dopamine neurons carrying ErbB1 and/or ErbB4. Exogenous EGF and NRG1 in the brain accelerate dopaminergic development and trigger ectopic hyperinnervation. The hyperdopaminergic innervation specifically persists in the globus pallidus and/or prefrontal cortex (mPFC). When the dopaminergic neurons are highly activated during and after adolescence, the excess amount of dopamine is released at the inappropriate sites, producing abnormal behavior and cognition.