Distinct Fos-Expressing Neuronal Ensembles in the Ventromedial Prefrontal Cortex Mediate Food Reward and Extinction Memories

Abstract

In operant learning, initial reward-associated memories are thought to be distinct from subsequent extinction-associated memories. Memories formed during operant learning are thought to be stored in "neuronal ensembles." Thus, we hypothesize that different neuronal ensembles encode reward-and extinction-associated memories. Here, we examined prefrontal cortex neuronal ensembles involved in the recall of reward and extinction memories of food self-administration. We first trained rats to lever press for palatable food pellets for 7 d (1 h/d) and then exposed them to 0, 2, or 7 daily extinction sessions in which lever presses were not reinforced. Twenty-four hours after the last training or extinction session, we exposed the rats to either a short 15 min extinction test session or left them in their homecage (a control condition). We found maximal Fos (a neuronal activity marker) immunoreactivity in the ventral medial prefrontal cortex of rats that previously received 2 extinction sessions, suggesting that neuronal ensembles in this area encode extinction memories. We then used the Daun02 inactivation procedure to selectively disrupt ventral medial prefrontal cortex neuronal ensembles that were activated during the 15 min extinction session following 0 (no extinction) or 2 prior extinction sessions to determine the effects of inactivating the putative food reward and extinction ensembles, respectively, on subsequent nonreinforced food seeking 2 d later. Inactivation of the food reward ensembles decreased food seeking, whereas inactivation of the extinction ensembles increased food seeking. Our results indicate that distinct neuronal ensembles encoding operant reward and extinction memories intermingle within the same cortical area.

Changes in Appetitive Associative Strength Modulates Nucleus Accumbens, But Not Orbitofrontal Cortex Neuronal Ensemble Excitability

“…It has been shown previously that Fos labels ensembles that are causally involved in the expression of conditioned behaviors (Koya et al, 2009;Fanous et al, 2012;Cruz et al, 2013;Warren et al, 2016). In addition, Fos expression requires sustained calcium signaling and ERK/MAPK phosphorylation (Cruz et al, 2013), but it is not necessarily a direct correlate of spike activity (Luckman et al, 1994).…”

“…However, recent studies have also suggested that extinction learning may result in the creation of a new neuronal ensemble that mediates the new CS-US contingency (Orsini et al, 2013;Warren et al, 2016). Warren et al (2016) performed pharmacogenetic lesioning of ventromedial prefrontal cortex Fos-expressing neurons in an operant food self-administration procedure and demonstrated that ablation of Fos-expressing neurons after extinction and food self-administration disinhibited and attenuated nonreinforced food-seeking, respectively.…”

“…Warren et al (2016) performed pharmacogenetic lesioning of ventromedial prefrontal cortex Fos-expressing neurons in an operant food self-administration procedure and demonstrated that ablation of Fos-expressing neurons after extinction and food self-administration disinhibited and attenuated nonreinforced food-seeking, respectively. This suggests that, in this area, extinction learning results in the recruitment of a new ensemble distinct from the ensemble activated during initial memory recall.…”

“…Exposure to food-associated cues activates brain areas that subserve motivational processes, such as the nucleus accumbens (NAc) and prefrontal cortex, which also play a pivotal role in encoding food-predictive cues and changes in cue-reinforcer contingencies (Annett et al, 1989;Schoenbaum et al, 2003;Day et al, 2006;Schoenbaum et al, 2007;Singh et al, 2010;Flagel et al, 2011;Petrovich, 2011;Burger and Berner, 2014;Warren et al, 2016). Moreover, there is now evidence indicating that, within both of these regions, associative memories may be encoded in sparsely activated subsets of neurons called neuronal ensembles (Pennartz et al, 1994;Koya et al, 2009;Fanous et al, 2012;Cruz et al, 2013;Warren et al, 2016;Whitaker et al, 2016).…”

“…Moreover, there is now evidence indicating that, within both of these regions, associative memories may be encoded in sparsely activated subsets of neurons called neuronal ensembles (Pennartz et al, 1994;Koya et al, 2009;Fanous et al, 2012;Cruz et al, 2013;Warren et al, 2016;Whitaker et al, 2016). These ensembles exhibit synaptic adaptations that are not observed in surrounding nonactivated neurons after learning Gouty-Colomer et al, 2016;Whitaker et al, 2016).…”