The lateral periaqeductal gray and its role in controlling the opposite behavioral choices of predatory hunting and social defense

Abstract

Evasion from imminent threats and prey attack are opposite behavioral choices critical to survival. Curiously, the lateral periaqueductal gray (LPAG) has been implicated in driving both responses. The LPAG responds to social threats and prey hunting while also drives predatory attacks and active defense. However, the LPAG neural mechanisms mediating these behaviors remain poorly defined. Here, we investigate how the LPAG mediates the choices of predatory hunting and evasion from a social threat. Pharmacogenetic inhibition in Fos DD-Cre mice of neurons responsive specifically to insect predation (IP) or social defeat (SD) revealed that distinct neuronal populations in the LPAG drive the prey hunting and evasion from social threats. We show that the LPAG provides massive glutamatergic projection to the lateral hypothalamic area (LHA). Optogenetic inhibition of the LPAG-LHA pathway impaired IP but did not alter escape/attack ratio during SD. We also found that pharmacogenetic inhibition of LHAGABA neurons impaired IP, but did not change evasion during SD. The results suggest that the LPAG control over evasion to a social attack may be regarded as a stereotyped response depending probably on glutamatergic descending projections. On the other hand, the LPAG control over predatory behavior involves an ascending glutamatergic pathway to the LHA that likely influences LHAGABA neurons driving predatory attack and prey consumption. The LPAG-LHA path supposedly provides an emotional drive for prey hunting and, of relevance, may conceivably have more widespread control on the motivational drive to seek other appetitive rewards.

Role of the rostral dorsomedial column of the periaqueductal gray during social defeat in rats

“…PMD lesions that led to substantial decreases in social defensive responses caused a significant reduction in FOS upregulation in the dorsomedial and lateral PAG. As previously discussed, the lateral PAG mediates escape responses during social interaction with an aggressive conspecific 6,7 . In this study, we examined the dorsomedial PAG to understand its putative roles in social defensive reactions.…”

“…As previously discussed, the lateral PAG mediates escape responses during social interaction with an aggressive conspecific. 6,7 In this study, we examined the dorsomedial PAG to understand its putative roles in social defensive reactions.…”

“…In animals exposed to an aggressive conspecific, we first examined how cytotoxic lesions in the PMD resulted in a drastic decrease in social defensive responses and influenced activation of its targets in the PAG. Considering the PMD's PAG targets, chemogenetic inhibition of lateral PAG neurons active in social defeat led to a reduction in escape responses during the agonistic encounter 6 . Moreover, the lateral PAG has also been found to drive social avoidance 7 .…”

“…Considering the PMD's PAG targets, chemogenetic inhibition of lateral PAG neurons active in social defeat led to a reduction in escape responses during the agonistic encounter. 6 Moreover, the lateral PAG has also been found to drive social avoidance. 7 Therefore, the lateral PAG mediates escape responses during social interaction with an aggressive conspecific.…”

Dynamics in brain activation and behaviour in acute and repeated social defensive motivated behaviour

“…Also, the mobilization of PAGdm,l was similar between the first and last exposure to social stress. These columns also receive projections from VMHvl and have subpopulations associated with escape or freezing behaviours 55,68,[71][72][73] . Therefore, these PAG columns may be important to the variation in social defence strategy, which could be related to the relationship between the activity of PMD and VMHvl.…”