Locomotor suppression by a monosynaptic amygdala to brainstem circuit

Abstract The control of locomotion is fundamental to vertebrate animal survival. Defensive situations require an animal to rapidly decide whether to run away or suppress locomotor activity to avoid detection. While much of the neural circuitry involved in defensive action selection has been elucidated, top-down modulation of brainstem locomotor circuitry remains unclear. Here we provide evidence for the existence and functionality of a monosynaptic connection from the central amygdala (CeA) to the mesencephalic locomotor region (MLR) that inhibits locomotion in unconditioned and conditioned defensive behavior in mice. We show that locomotion stimulated by airpuff coincides with increased activity of MLR glutamatergic neurons. Using retrograde tracing and ex vivo electrophysiology, we find that the CeA makes a monosynaptic connection with the MLR. In the open field, in vivo stimulation of this projection suppressed spontaneous locomotion, whereas inhibition of this projection had no effect. However, inhibiting CeA terminals within the MLR increased both neural activity and locomotor responses to airpuff. Finally, using a conditioned avoidance paradigm known to activate CeA neurons, we find that inhibition of the CeA projection increased successful escape, whereas activating the projection reduced escape. Together these results provide evidence for a new circuit substrate influencing locomotion and defensive behaviors.