Distinct projections from the prelimbic cortex modulate active avoidance

Abstract

Avoiding threatening stimuli is a survival mechanism that can become maladaptive when avoidance interferes with other goal‐directed behaviors. For example, when an individual is seeking food, a threatening stimulus may be encountered, leading to an avoidance response, which comes at a cost of obtaining food. To model this behavior, we used an active avoidance task in which food‐restricted rats learn to step onto a platform to avoid a tone‐signaled shock, at the cost of obtaining a sucrose pellet. Activity in prelimbic cortex (PL), basolateral amygdala (BLA), and ventral striatum (VS) are necessary for the expression of platform‐mediated active avoidance (PMA) (Bravo‐Rivera, et. al., 2014), suggesting that these structures form a neural circuit to regulate PMA. We recently reported that inhibitory tone responses in PL signal the avoidability of shock, and opposing these responses using 4Hz photoactivation impaired avoidance (Diehl, et. al., 2018). Here, we want to know if PL inhibition signals downstream structures that are necessary for avoidance (i.e. VS and BLA), using an optogenetic approach. Photoactivating PL‐VS projections using Channelrhodopsin (ChR2) impaired avoidance (eYFP 88% (n=12) vs. ChR2 22% (n=8), p<0.0001), whereas photosilencing PL‐VS projections using Archaerhodopsin (ArchT) had no effect, suggesting that inhibition of this pathway promotes avoidance. Additionally, photoactivating PL‐BLA projections accelerated avoidance (eYFP 75% (n=9) vs. ChR2 88% (n=8), p=0.017), and photosilencing PL‐BLA projections impaired avoidance (eYFP 77% (n=9) vs. ArchT 40% (n=7), p=0.026), suggesting that excitation of this pathway promotes avoidance. Overall, these findings suggest that distinct PL projections have opposing roles in controlling avoidance by driving or suppressing avoidance.Support or Funding InformationThis work was supported by NIH grants R37‐MH058883 and P50‐MH086400 (Conte Center) to GJQ; F32‐MH105185 to MMD; 5T34‐GM00782140 to GRB, 5R25‐GM097635 to JIG and VVV; 5R25‐GM061151 to GRB, FDG and JMS.