Abstract

Objectives: There is conflicting evidence about the role of the infralimbic prefrontal cortex (IL-PFC) in the extinction of appetitive Pavlovian conditioning. Here, we tested the hypothesis that IL-PFC activity mediates the inhibition of conditioned behaviour following extinction, and predicted that augmenting IL-PFC activity would reduce sucrose-induced reinstatement and spontaneous recovery of Pavlovian conditioned sucrose-seeking.
Methods: Male, Long-Evans rats (Charles River) received bilateral cannulae or unilateral microinfusions of a viral vector coding for Channelrhodopsin-2 (ChR2) and enhanced yellow fluorescent protein (eYFP), or eYFP only, and optical fiber implantation targeting the IL-PFC. During Pavlovian conditioning, presentations of an auditory conditioned stimulus (CS; 10 s, 14 trials/session, VT-140 s) were paired with a 10% w/v sucrose solution (0.2 ml; 2.8 ml/session). The same procedure was repeated during extinction and test sessions, except that sucrose was omitted during CS trials. The effect of optically stimulating (473 nm, 5 ms, 20 Hz, 30 mW) IL-PFC neurons during CS trials in spontaneous recovery tests was assessed at 24 h after a single extinction session, and also 26 days later. In two separate groups of rats, the effect of enhancing IL-PFC activity using pre-session microinfusions of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA; 0 or 0.3 nmol/µl/side) or optical stimulation during CS trials on sucrose-induced reinstatement of sucrose-seeking behaviour was assessed. The ability of optical stimulation to induce Fos expression was also measured in separate animals.
Results: Optical stimulation of IL-PFC neurons reduced spontaneous recovery after a delay of 26 days, but not 24 h. Reinstatement was reduced by both intra-IL-PFC AMPA and by optical stimulation. Optical stimulation increased Fos expression in ChR2 expressing neurons compared to eYFP controls.
Conclusions: Our results show that the IL-PFC plays a key role in maintaining the inhibition of appetitive, Pavlovian conditioned behaviour following extinction.