Neural correlates of appetitive–aversive interactions in Pavlovian fear conditioning

Abstract

We used Pavlovian counterconditioning in rats to identify the neural mechanisms for appetitive -aversive motivational interactions. In Stage I, rats were trained on conditioned stimulus (CS) -food (unconditioned stimulus [US]) pairings. In Stage II, this appetitive CS was transformed into a fear CS via pairings with footshock. The development of fear responses was retarded in rats that had received Stage I appetitive training. This counterconditioning was associated with increased levels of phosphorylated mitogen activated protein kinase immunoreactivity (pMAPK-IR) in several brain regions, including midline thalamus, rostral agranular insular cortex (RAIC), lateral amygdala, and nucleus accumbens core and shell, but decreased expression in the ventrolateral quadrant of the midbrain periaqueductal gray. These brain regions showing differential pMAPK-IR have previously been identified as part of the fear prediction error circuit. We then examined the causal role of RAIC MAPK in fear learning and showed that Stage II fear learning was prevented by RAIC infusions of the MEK inhibitor PD098059 (0.5 mg/hemisphere). Taken together, these results show that there are opponent interactions between the appetitive and aversive motivational systems during fear learning and that the transformation of a reward CS into a fear CS is linked to heightened activity in the fear prediction error circuit.

Reward anticipation and punishment anticipation are instantiated in the brain via opponent mechanisms

“…In the present study, PCC and lateral OFC clusters showed differential activation to reward and punishment motivation, consistent with studies implicating these regions in valencerelated activation (Litt et al, 2011). Greater lateral OFC activation to punishment than to reward motivation is consistent with a medial-lateral gradient for reward versus punishment processing in OFC (Kringelbach & Rolls, 2004;O'Doherty, Kringelbach, Rolls, Hornak, & Andrews, 2001). It has been reported that potential punishments are more motivating or salient than potential gains (i.e., Kahneman & Tversky, 1979;Sokol-Hessner et al, 2009).…”

Adolescent conditioning affects rate of adult fear, safety and reward learning during discriminative conditioning

“…Dysregulations in processing these stimuli can lead to psychiatric conditions, like posttraumatic stress disorder (PTSD) and addiction. Not only does the comorbidity between these disorders 1 , 2 suggest substantial interaction of reward and fear processing systems, rodent models have also established a tight cross talk on a behavioural 3 , molecular (rev. in 4 ) and anatomical/circuit level 5 – 12 .…”

Loss of dopamine D1 receptors and diminished D1/5 receptor-mediated ERK phosphorylation in the periaqueductal gray after spinal cord lesion

“…Since coupling of ERK and CREB phosphorylation to D1 receptor activation has been well established in other brain regions (Brami-Cherrier et al, 2002; Acquas 2007; Papadeas et al, 2008; Pascoli et al, 2012), and as ERK1,2 is phosphorylated in the PAG in response to diverse stimuli (Gioia et al, 2005, Macey et al, 2009; Nasser and McNally, 2013; Sanna et al, 2014; Macey et al, 2015), we selected pERK1,2 and pCREB as markers to assess D1 receptor-mediated signal transduction. As a first step toward addressing this point, we used an in vivo approach to investigate the effect of administration of SKF 81297, a D1/5 receptor agonist, on ERK1,2 and CREB phosphorylation in the PAG of naïve mice.…”