Defensive Vocalizations and Motor Asymmetry Triggered by Disinhibition of the Periaqueductal Gray in Non-human Primates

Rapid and reflexive responses to threats are present across phylogeny. The neural circuitry mediating reflexive defense reactions has been well-characterized in a variety of species, for example, in rodents and cats, the detection of and species-typical response to threats is mediated by a network of structures including the midbrain tectum (deep and intermediate layers of the superior colliculus [DLSC]), periaqueductal gray (PAG), and forebrain structures such as the amygdala and hypothalamus. However, relatively little is known about the functional architecture of defense circuitry in primates. We have previously reported that pharmacological activation of the DLSC evokes locomotor asymmetry, defense-associated vocalizations, cowering behavior, escape responses, and attack of inanimate objects (Holmes et al., 2012; DesJardin et al., 2013; Forcelli et al., 2016). Here, we sought to determine if pharmacological activation of the PAG would induce a similar profile of responses. We activated the PAG in three awake, behaving macaques by microinfusion of GABA-A receptor antagonist, bicuculline methiodide. Activation of PAG evoked defense-associated vocalizations and postural/locomotor asymmetry, but not motor defense responses (e.g., cowering, escape behavior). These data suggest a partial dissociation between the role of the PAG and the DLSC in the defense network of macaques, but a general conservation of the role of PAG in defense responses across species.