As animals forage, they must obtain useful targets by orchestrating appropriate actions that range from searching to chasing, biting and carrying. Here, we reveal that neurons positive for the α subunit of Ca/calmodulin-dependent kinase II (CaMKIIα) in the medial preoptic area (MPA) that send projections to the ventral periaqueductal gray (vPAG) mediate these target-directed actions in mice. During photostimulation of the MPA-vPAG circuit, mice vigorously engaged with 3D objects and chased moving objects. When exposed to a cricket, they hunted down the prey and bit it to kill. By applying a head-mounted object control with timely photostimulation of the MPA-vPAG circuit, we found that MPA-vPAG circuit-induced actions occurred only when the target was detected within the binocular visual field. Using this device, we successfully guided mice to navigate specified routes. Our study explains how the brain yields a strong motivation to acquire a target object along the continuum of hunting behavior.

Repetitive exposure to fear-associated targets is a typical treatment for patients with panic or post-traumatic stress disorder (PTSD). The success of exposure therapy depends on the active exploration of a fear-eliciting target despite an innate drive to avoid it. Here, we found that a circuit running from CaMKIIα-positive neurons of the medial preoptic area to the ventral periaqueductal gray (MPA-vPAG) facilitates the exploration of a fear-conditioned zone and subsequent fear extinction in mice. Activation or inhibition of this circuit did not induce preference/avoidance of a specific zone. Repeated entries into the fear-conditioned zone, induced by the motivation to chase a head-mounted object due to MPA-vPAG circuit photostimulation, facilitated fear extinction. Our results show how the brain forms extinction memory against avoidance of a fearful target and suggest a circuit-based mechanism of exposure therapy.

In the version of this article initially published, a sentence in the fifth paragraph of the Results read, "Immunohistochemistry revealed that VGLUT2+ MPA neurons rarely expressed CaMKIIα , which is a putative marker for subcortical glutamatergic neurons. " It should have read, "Immunohistochemistry revealed that CaMKIIα + MPA neurons rarely expressed VGLUT2, which is a putative marker for subcortical glutamatergic neurons. " The error has been corrected in the HTML and PDF versions of the article. In the supplementary information originally posted online, the wrong version of Supplementary Fig. 1 was posted and some of the supplementary videos were interchanged. In the corrected Supplementary Fig. 1, the top right subpanel was added and the original Supplementary Fig. 1a was divided into 1a and 1b, with subsequent panels incremented accordingly. The legend was changed from "a. Schematic illustrating electrical lesioning of the rat anterior hypothalamus. Electrical lesion areas (gray) in five representative brain sections are depicted. Scale bar, 1 mm" to "a. Repetitive electrical stimulations of the anterior hypothalamus using bipolar electrodes (Left) caused a lesion at the hypothalamic area (middle, marked by asterisk) successfully in 7 rats (Right, overlapped images of brain sections located from the bregma −0.24 mm). Scale bar, 1 mm. b. Electrical lesion areas (gray) in five representative brain sections from anterior to posterior are depicted. " The errors have been corrected online.Published: xx xx xxxx https://doi