Divergent projections of the prelimbic cortex bidirectionally regulate active avoidance.

Maria M Diehl,Jonathan Morán-Sierra,Gregory J Quirk,Viviana P Valentín-Valentín,Jorge M Iravedra-Garcia,Fabiola N Gonzalez-Diaz,Gabriel Rojas-Bowe

doi:10.7554/elife.59281

Abstract

The prefrontal cortex (PFC) integrates incoming information to guide our actions. When motivation for food-seeking competes with avoidance of danger, the PFC likely plays a role in selecting the optimal choice. In platform-mediated active avoidance, rats avoid a tone-signaled footshock by stepping onto a nearby platform, delaying access to sucrose pellets. This avoidance requires prelimbic (PL) PFC, basolateral amygdala (BLA), and ventral striatum (VS). We previously showed that inhibitory tone responses of PL neurons correlate with avoidability of shock (Diehl et al., 2018). Here, we optogenetically modulated PL terminals in VS and BLA to identify PL outputs regulating avoidance. Photoactivating PL-VS projections reduced avoidance, whereas photoactivating PL-BLA projections increased avoidance. Moreover, photosilencing PL-BLA or BLA-VS projections reduced avoidance, suggesting that VS receives opposing inputs from PL and BLA. Bidirectional modulation of avoidance by PL projections to VS and BLA enables the animal to make appropriate decisions when faced with competing drives.

Highlights

The prefrontal cortex (PFC) controls goal-directed behaviors by integrating sensory, motor, and memory information to guide an individual’s actions (Fuster, 1997; Miller and Cohen, 2001; Kesner and Churchwell, 2011)
Because PL projects densely to the ventral striatum (VS; Sesack et al, 1989; Vertes, 2004), we hypothesized that inhibitory responses within PL neurons projecting to the VS would promote avoidance
We found that photoactivation of PL-VS projections impaired avoidance, whereas photoactivation of PL-basolateral amygdala (BLA) projections promoted avoidance, suggesting a prefrontal circuit that bidirectionally modulates avoidance behavior

Summary

Introduction

The prefrontal cortex (PFC) controls goal-directed behaviors by integrating sensory, motor, and memory information to guide an individual’s actions (Fuster, 1997; Miller and Cohen, 2001; Kesner and Churchwell, 2011). A leading hypothesis is that the PFC evaluates possible outcomes in the presence of competing drives (Ridderinkhof et al, 2004; Rushworth and Behrens, 2008; Bissonette, Powell and Roesch, 2013; Saunders et al, 2017), such as seeking food rewards in the presence of a potential threat (Aupperle et al, 2015; Friedman et al, 2015; Schumacher, Vlassov and Ito, 2016; Bublatzky, Alpers and Pittig, 2017) This situation has been modeled in rodents using the platform-mediated active avoidance (PMA) task, in which foodrestricted rats learn to avoid a tone-signaled shock by moving to a nearby platform, at the cost of delaying access to sucrose pellets (Bravo-Rivera et al, 2014). PL projects heavily to the ventral striatum (VS) and the basolateral amygdala (BLA) (Sesack et al, 1989; Vertes, 2004), both of which are necessary for PMA (Bravo-Rivera et al, 2014) as well as other types of active avoidance (Darvas, Fadok and Palmiter, 2011; Ramirez et al, 2015)

Methods

Results

Conclusion