However, our inclusion of non-extinction controls showed that this disruption was not indicative of a lack of extinction learning. Strength and similarity guided group-level brain functional network construction for MCI diagnosis, Resting-state functional magnetic resonance imaging (rs-fMRI). (C) Behavioural design for Overexpectation. Freezing increased across days and the rate of acquisition was similar across groups as shown by a significant linear trend (tone: F(1, 45) = 69.77, p < 0.001, ηp2 = 0.61, 95% CI [1.20, 1.96]; flash: F(1, 45) = 166.96, p < 0.001, ηp2 = 0.79, 95% CI [1.79, 2.46]), and no linear trend x training x drug interaction (tone: F(1, 45) = 0.069, p = 0.79, 95% CI [-0.84, 1.04]; flash: F(1, 45) = 0.041, p = 0.84, 95% CI [-0.75, 0.88]). Our candidate was the lateral orbitofrontal cortex (lOFC), a structure strongly linked to reward learning (e.g., Gardner et al., 2019; Padoa-Schioppa and Assad, 2006; Rich and Wallis, 2016). The tips of the guide cannulae were aimed at the IL , the following coordinates were used: 2.9 mm anterior to bregma, 2.6 mm lateral to the midline at a 30° angle (bypassing the prelimbic cortex), and 4.2 mm ventral to bregma. We use cookies to help provide and enhance our service and tailor content and ads. Conditioned fear was acquired to the auditory and visual cues (Figure 3D). Identical infusions were also given to the control rats that did not receive extinction. or, by University of Pennsylvania, The gun violence seen in popular PG-13 movies aimed at children and teenagers has more than doubled since the rating was introduced in 1984. Rats in the extinction condition (EXT) received non-reinforced presentations of the target cue. There was a significant linear trend across trials (F(1, 51)=55.35, p<0.001, ηp2 = 0.52, 95% CI [−0.89,–0.51]), confirming a decline in responding across Test, a linear trend x training interaction (F(1, 51)=30.76, p<0.001, ηp2 = 0.38, 95% CI [0.58, 1.50]) confirming that only the control groups showed a decline across Test, but there was no linear trend x training x drug interaction (F(1, 51)=0.007, p=0.93, 95% CI [−0.54, 0.51]). A significant linear trend (F(1, 33)=44.82, p<0.001, ηp2 = 0.58, 95% CI [0.76, 1.42]) and no linear trend x training x drug interaction (F(1, 33)=0.84, p=0.37, 95% CI [−1.12, 0.52]) indicate that fear increased across trials but the rate of increase was similar across groups. In our study of the neurobiology of fear reduction, we also chose to move beyond the traditional fear circuit. The information you enter will appear in your e-mail message and is not retained by Medical Xpress in any form. All rats were then tested for conditioned responding to the target cue the following day. Do-Monte et al., 2015), while others report a retardation (e.g., Sierra-Mercado et al., 2011) or facilitation (e.g., Mendoza et al., 2015; Lay et al., 2019). Prior to overexpectation training the rats received either infusions of muscimol and baclofen (0.1 mM muscimol-1 mM baclofen, M/B) or vehicle into the IL. Click here to sign in with Your email address is used only to let the recipient know who sent the email. The dissociation of function reported here flies in the face of a parsimonious explanation for fear reduction in the IL and lOFC. Overexpectation-M/B (filled black), n = 12; overexpectation-vehicle (open black), n = 11; control-M/B (filled burgundy), n = 12; control-vehicle (open burgundy), n = 9. The remaining half of the cohort received no training during this phase. For this reason, the word "extinction" in the title could be "reduction". Thus, the pattern observed in the IL inactivation animals is consistent with inhibitory learning that likely involves cue-response associations. This is unlikely to be the case in overexpectation because responding is maintained at high levels due to shock delivery. Finally, the dissociation of function between the IL and lOFC is in line with data implicating IL activation during reduction of conditioned fear using a habituation method (Furlong et al., 2016), as well as research implicating the lOFC in cue-outcome associations (Lichtenberg et al., 2017; Zhang and Li, 2018, Takahashi et al., 2009, Asok et al., 2013). Infusions of M/B or vehicle into the lateral OFC occurred 30 min prior to the start of the extinction session. All rats were conditioned to fear a novel cue (steady light or white-noise, counterbalanced, Figure 4C). A mixed ANOVA revealed a main effect of training (F(1, 51)=56.68, p<0.001, 95% CI [−1.89,–0.96], d = 1.88), and a main effect of drug (F(1, 51)=5.38, p=0.024, 95% CI [−0.03, 0.91], d = 0.43), but no training x drug interaction (F(1, 51)=0.18, p=0.67, 95% CI [−0.39, 0.55]). This allowed us to assess the generality of the role of the lOFC in extinction. Extinction-M/B (filled black), n = 16; extinction-vehicle (open black), n = 16; control-M/B (filled burgundy), n = 11; control-vehicle (open burgundy), n = 12. In the context of fear learning, extinction involves the dramatic reduction in fear-related behaviours typically observed after presenting a previously established signal for an aversive event (i.e., a tone paired with shock; tone →shock) in the absence of that event (tone presented alone; tone → nothing). This yielded four sub-conditions: extinction-M/B, extinction-vehicle, control-M/B, and control-vehicle. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. The content is provided for information purposes only. (C) Behavioural design for Extinction. Illumination of each chamber was provided by a near-infrared light source (NIR-200) mounted on the back wall of each cabinet. Location of cannula placements for (A) drug- and (B) vehicle-infused rats in the IL cortex in the overexpectation experiment as verified based on the atlas of Paxinos and Watson, 1997. Freezing to the cue across extinction did not differ between extinction-M/B and extinction-vehicle rats. The numbers of rats excluded from each experiment based on incorrect placements or infection were fourteen in Experiment 1, three in Experiment 2, and one in Experiment 3. Your feedback will go directly to Science X editors. Behavioural data are represented as mean + SEM percent levels of freezing during the cue period for (D) Conditioning, (E) Extinction, and (F) Test for Extinction of the target stimulus. On days 1 to 6, rats were placed into the conditioning context for 20 min sessions. Infusions of M/B in the lOFC had no effect on freezing to the compound cues during the overexpectation phase (Figure 3E). The first relates to the number of trials necessary for learning in extinction and overexpectation. On day 1, rats were placed in the conditioning context, and after a 5 min adaption period, received four, 30 s paired presentations of a steady light or a white-noise (counterbalanced across rats) and shock (0.5 mA, 1 s).

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