Endocannabinoids and dopamine balance basal ganglia output

AbstractThe entopeduncular nucleus is one of the basal ganglia’s output nuclei, thereby controlling basal ganglia information processing. Entopeduncular nucleus neurons integrate GABAergic inputs from the striatum and the globus pallidus and glutamatergic inputs from the subthalamic nucleus. We show that endocannabinoids and dopamine interact to modulate the long-term plasticity of all the primary afferents to the entopeduncular nucleus. Our results suggest that dopamine-endocannabinoids interplay determines the balance of the direct or indirect dominance of entopeduncular nucleus output. Furthermore, we demonstrate that, despite the lack of axon collaterals, information is transferred between neighboring neurons in the entopeduncular nucleus via endocannabinoids diffusion. These results transform the prevailing view of the entopeduncular nucleus as a feedforward “relay” nucleus to an intricate control unit, which may play a vital role in the process of action selection.