ABA Renewal Research Articles

Renewal of conditioned fear in male and female rats.

Pavlovian extinction reduces the performance of conditioned responses and occurs when the conditioned stimulus (CS) is repeatedly presented in the absence of the unconditioned stimulus (US). However, when the CS is experienced in a context that is different from the extinction context, there is a recovery of the conditioned response, a phenomenon known as renewal. There is some evidence that the renewal of appetitive conditioning is influenced by sex, with females failing to exhibit renewed responding. Further, there is recent evidence that renewal of fear might also not occur in female rats. In both appetitive and fear preparations, the lack of renewal in females has been postulated to be related to cycling ovarian hormones. Therefore, in Experiments 1 and 2, we directly compared fear renewal in males and females (Experiment 1) as well as ovariectomized (OVX) females (Experiment 2) when conditioning occurred in Context A, extinction in B, and testing in A (ABA renewal). Experiments 3 and 4 examined renewal when conditioning and extinction occurred in A and testing occurred in B (AAB renewal). In all experiments, renewal was not significantly different between male and female rats. Further, in Experiments 2 and 4, renewal did not differ between males, intact females, and OVX females. Additionally, in each experiment, there was no evidence that context excitation and/or inhibition contributed to renewal; instead suggesting that renewal was controlled by an occasion-setting mechanism. Overall, these results suggest little evidence for the role of sex in renewal of conditioned freezing and also indicate that cycling ovarian hormones have little role in the strength of renewal in female rats. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Contextual modulation of human associative learning following novelty-facilitated extinction, counterconditioning, and conventional extinction.

The expression of an association between a conditioned stimulus (CS) and an unconditioned stimulus (US) can be attenuated by presenting the CS by itself (i.e., extinction, Ext). Though effective, Ext is susceptible to recovery effects such as renewal, spontaneous recovery, and reinstatement. Dunsmoor et al. (2015, 2019) have proposed that pairing the CS with a neutral outcome (novelty-facilitated Ext [NFE]) could offer better protection against recovery effects than Ext. Though NFE has been compared to Ext, it has rarely been compared to counterconditioning (CC), a similar procedure except that the CS is paired with a US having a valence opposite to the US used in initial training. We report two aversive conditioning experiments using the rapid-trial streaming procedure with human participants that compare the efficacies and susceptibilities to ABA renewal of Ext, CC, and NFE. Associative learning was assessed through expectancy learning and evaluative conditioning. CC and NFE equally decreased anticipation of the US in the presence of the CS (i.e., expectancy learning). Depending on how the CS-US association was probed, they were either as or more effective at doing so than Ext. All three interference treatments were equally susceptible to context manipulations. Only CC clearly altered the valence of the CS (i.e., evaluative conditioning). Valence ratings after Ext, CC, and NFE, as well as a no-interference control condition, were all equally susceptible to context effects. Overall, the present study does not support the assertion that NFE is consistently more resistant to recovery effects than Ext. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

ABA and AAB renewal of alcohol seeking in rats are reduced by exposure to beer before extinction

Three experiments with rats examined the impact of a retrieval-extinction procedure on ABA and AAB renewal of instrumental learning. In all experiments, rats were trained to run down an alley for alcoholic beer in Context A. Then, the instrumental response underwent extinction, which was conducted in Context B for Experiments 1 and 2, and in Context A for Experiment 3. In each experiment, one group of animals received a brief exposure to the beer prior to each extinction session, whereas this beer exposure was omitted for a second group. Moreover, Experiment 2 comprised a third group that was exposed to non-alcoholic beer before each extinction session. Finally, all rats were tested in their extinction context and in a second context, which was Context A for Experiments 1 and 2, and Context B for Experiment 3. We found ABA (Experiments 1 and 2) and AAB (Experiment 3) renewal of beer seeking in those animals for which beer exposure prior to extinction was omitted. However, response recovery was not evident when animals received exposure to beer before extinction, regardless of whether alcoholic or non-alcoholic beer was used. Our results suggest that the renewal of alcohol seeking can be prevented by means of the retrieval-extinction paradigm.

The effect of gradual extinction training on the renewal of electrodermal conditional responses.

Extinction, the repeated presentation of a conditional stimulus (CS) without the unconditional stimulus (US), is the standard paradigm to reduce conditional responding acquired by the repeated pairing of CS and US in acquisition. However, this reduction of conditional responding is prone to relapse. In rodent fear-conditioning, gradual extinction, the fading out of CS-US pairings during extinction, has been shown to reduce the return of fear. The current study replicated the gradual extinction procedure in human fear conditioning and assessed whether it reduced the return of fear due to ABA renewal and reacquisition. During extinction, one group received standard extinction, a second received gradual extinction (increasing the spacing of USs presented after the 1st, 3rd, 6th, 10th, and 15th CS+ trials), and a third received reversed extinction training (decreasing the spacing of USs presented after the 1st, 6th, 10th, 13th, and 15th CS+ trials). Larger renewal and faster reacquisition of differential electrodermal responses to CS+ and CS- were expected after standard and reversed extinction than after gradual extinction training. The results were inconclusive due to the failure to find extinction of differential electrodermal responses and US expectancy ratings in both gradual and reversed extinction groups. Despite successful extinction in group standard, renewal was only observed in US expectancy. Visualization of US expectancy ratings during extinction suggested that potential identification of the US presentation patterns during extinction in the gradual and reversed groups delayed extinction learning.

Signalling unpaired unconditional stimuli during extinction does not impair their effect to reduce renewal of conditional fear

Presenting unpaired unconditional stimuli (US) during extinction training reduces the renewal of conditional fear due to context change and slows re-acquisition. The present study investigated whether this reduced return of fear is mediated by Pavlovian inhibitory conditioning to the conditional stimulus paired with the US during acquisition (CS+) that is acquired when this stimulus is presented without the US in an excitatory extinction context. Using an ABA renewal paradigm that trained extinction in a context different from acquisition and renewal test, participants either received no USs (Standard), five unsignalled US presentations (Unsignalled) or five presentations of the US preceded by a novel, third CS (Signalled) during extinction training. Extinction was followed by tests for renewal and re-acquisition. Replicating previous results, renewal of electrodermal conditional responses was observed in group Standard, but not in group Unsignalled. Signalling the additional USs, and thus reducing context conditioning and the potential for inhibitory conditioning, did not reduce their effect in that renewal was absent in group Signalled. These results are inconsistent with an inhibitory conditioning account of the effects of unpaired US presentations during extinction. A trial sequence learning account or an arousal account may explain the effects of unpaired presentations of the US during extinction.

Renewal of instrumental avoidance in humans.

The ABA renewal effect occurs when behavior is trained in one context (A), extinguished in a second context (B), and the test occurs in the training context (A). Two mechanisms that explain ABA renewal are context summation at the test and contextual modulation of extinction learning, with the former being unlikely if both contexts have a similar associative history. In two experiments, we used within-subjects designs in which participants learned to avoid a loud noise (unconditioned stimulus) signaled by discrete visual stimuli (conditioned stimuli [CSs]), by pressing the space bar on the computer keyboard. The training was conducted in two contexts, with a different pair of CSs (CS+ and CS-) trained in each context. During extinction, CS+ and CS- stimuli were presented in the alternative context from that of training, and participants were allowed to freely respond, but no loud noise was presented. Finally, all CSs were tested in both contexts, resulting in a within-subjects ABA versus ABB comparison. Across experiments, participants increased avoidance responses during training and decreased them during extinction, although Experiment 2 revealed less extinction. During the test, responding was higher when CS+ were tested in the training context (ABA) versus the extinction context (ABB), revealing the renewal of instrumental avoidance. Experiment 2 also measured expectancy after the avoidance test and revealed a remarkable similarity between avoidance responses and expectancy ratings. This study shows the renewal of instrumental avoidance in humans, and the results suggest the operation of a modulatory role for the context in renewal, similar to the occasion setting of extinction learning by the context. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Microstructural properties of attention-related white matter tracts are associated with the renewal effect of extinction

The tendency to show the renewal effect of extinction appears as an intra-individually stable, reproducible processing strategy associated with differential patterns of BOLD activation in hippocampus, iFG and vmPFC, as well as differential resting-state functional connectivity between prefrontal regions and the dorsal attention network. Also, pharmacological modulations of the noradrenergic system that influence attentional processing have partially different effects upon individuals with (REN) and without (NoREN) a propensity for renewal. However, it is as yet unknown whether REN and NoREN individuals differ regarding microstructural properties in attention-related white matter (WM) regions, and whether such differences are related to noradrenergic processing. In this diffusion tensor imaging (DTI) analysis we investigated the relation between microstructural properties of attention-related WM tracts and ABA renewal propensity, under conditions of noradrenergic stimulation by means of the noradrenergic reuptake inhibitor atomoxetine, compared to placebo.Fractional anisotropy (FA) was higher in participants with noradrenergic stimulation (ATO) compared to placebo (PLAC), the effect was predominantly left-lateralized and based on the comparison of ATO REN and PLAC REN participants. In REN participants of both treatment groups, FA in several WM tracts showed a positive correlation with the ABA renewal level, suggesting higher renewal levels were associated with higher microstructural integrity. These findings point towards a relation between microstructural properties of attention-related WM tracts and the propensity for renewal that is not specifically dependent on noradrenergic processing.

Involvement of Pre-limbic Cortex-Nucleus accumbens projections in Context-Induced alcohol seeking

Alcohol use disorder (AUD) remains a critical public health issue worldwide, characterized by high relapse rates often triggered by contextual cues. This research investigates the neural mechanisms behind context-induced reinstatement of alcohol-seeking behavior, focusing on the nucleus accumbens and its interactions with the prelimbic cortex, employing Male Long-Evans rats in an ABA renewal model. In our experimental setup, rats were trained to self-administer 10 % ethanol in Context A, followed by extinction of lever pressing in the presence of discrete cues in Context B. The context-induced reinstatement of ethanol-seeking was then assessed by re-exposing rats to Context A or B under extinction conditions, aiming to simulate the environmental cues’ influence on relapse behaviors. Three experiments were conducted: Experiment 1 utilized Fos-immunohistochemistry to examine neuronal activation in the nucleus accumbens; Experiment 2 applied the baclofen + muscimol inactivation technique to probe the functional importance of the nucleus accumbens core; Experiment 3 used Fos-immunofluorescence along with Retrobeads injection to investigate activation of neurons projecting from the prelimbic cortex to the nucleus accumbens core. Our findings revealed significant increases in Fos-immunoreactive nuclei within the nucleus accumbens core and shell during the reinstatement phase in Context A, underscoring the environment’s potent effect on ethanol-seeking behavior. Additionally, inactivation of the nucleus accumbens core markedly reduced reinstatement, and there was a notable activation of neurons from the prelimbic cortex to the nucleus accumbens core in the ethanol-associated context. These results highlight the critical role of the nucleus accumbens core and its corticostriatal projections in the neural circuitry underlying context-driven ethanol seeking.

The effects of a retrieval cue on renewal of conditioned responses in human appetitive conditioning

Contextual renewal of reward anticipation may be one potential mechanism underlying relapse in eating and substance use disorders. We therefore tested retrieval cues, a method derived from an inhibitory retrieval-based model of extinction learning to attenuate contextual renewal using an appetitive conditioning paradigm. A pilot study was carried out in Experiment 1 to validate a differential chocolate conditioning paradigm, in which a specific tray was set up as a conditioned stimulus (CS) for eating chocolate (unconditioned stimulus, US). Using an ABA renewal design in Experiment 2, half of the participants were presented with a retrieval cue in the acquisition phase (group AC) and the other half in the extinction phase (group EC). Presentation of the retrieval cue in the EC was associated with reduced renewal of US-expectancy, while there was a clear renewal effect for US-expectancy in the AC. One limitation was the difference in cue presentations between both groups due to the number of trials in acquisition and extinction. Experiment 3 therefore aimed at replicating the results of Experiment 2, but with fewer cue presentations for the EC to match the AC. No significant group differences were observed indicating no effect of the retrieval cue. Theoretical and clinical implications in light of the differing results are discussed.

Dissimilarities of neural representations of extinction trials are associated with extinction learning performance and renewal level.

Renewal of extinguished responses is associated with higher activity in specific extinction-relevant brain regions, i.e., hippocampus (HC), inferior frontal gyrus (IFG), and ventromedial PFC (vmPFC). HC is involved in processing of context information, while IFG and vmPFC use such context information for selecting and deciding among competing response options. However, it is as yet unknown to what extent trials with changed versus unchanged outcome, or extinction trials that evoke renewal (i.e., extinction context differs from acquisition and test context: ABA trials) and trials that do not (i.e., same context in all phases: AAA trials) are represented differentially in extinction-relevant brain regions. In this study, we applied representational similarity analysis (RSA) to determine differences in neural representations of these trial types and their relationship to extinction error rates and renewal level. Overall, individuals with renewal (REN) and those without (NoREN) did not differ significantly in their discrimination levels between ABA and AAA extinction trials, with the exception of right posterior HC, where REN exhibited more pronounced context-related discrimination. In addition, higher dissimilarity of representations in bilateral posterior HC, as well as in several IFG regions, during extinction learning was linked to lower ABA renewal rates. Both REN and NoREN benefitted from prediction error feedback from ABA extinction errors for context- and outcome-related discrimination of trials in IFG, vmPFC, and HC, but only the NoREN group also benefitted from error feedback from AAA extinction errors. Thus, while in both groups the presence of a novel context supported formation of distinct representations, only in NoREN the expectancy violation of the surprising change of outcome alone had a similar effect. In addition, only in NoREN context-related discrimination was linked to error feedback in vmPFC. In summary, the findings show that context- and outcome-related discrimination of trials in HC, vmPFC, and IFG is linked to extinction learning errors, regardless of renewal propensity, and at the same time point towards differential context processing strategies in REN and NoREN. Moreover, better discrimination of context-related trials during extinction learning promotes less renewal during extinction recall, suggesting that renewal may be related to suboptimal context-related trial discrimination.

Glutamatergic neurons in ventral pallidum modulate heroin addiction via epithalamic innervation in rats.

Glutamatergic neurons in ventral pallidum (VPGlu) were recently reported to mediate motivational and emotional behavior, but its role in opioid addiction still remains to be elucidated. In this study we investigated the function of VPGlu in the context-dependent heroin taking and seeking behavior in male rats under the ABA renewal paradigm. By use of cell-type-specific fiber photometry, we showed that the calcium activity of VPGlu were inhibited during heroin self-administration and context-induced relapse, but activated after extinction in a new context. The drug seeking behavior was accompanied by the decreased calcium signal of VPGlu. Chemogenetic manipulation of VPGlu bidirectionally regulated heroin taking and seeking behavior. Anterograde tracing showed that the lateral habenula, one of the epithalamic structures, was the major output region of VPGlu, and its neuronal activity was consistent with VPGlu in different phases of heroin addiction and contributed to the motivation for heroin. VPGlu axon terminals in LHb exhibited dynamic activity in different phases of heroin addiction. Activation of VPGlu-LHb circuit reduced heroin seeking behavior during context-induced relapse. Furthermore, the balance of excitation/inhibition from VP to LHb was shifted to enhanced glutamate transmission after extinction of heroin seeking motivation. Overall, the present study demonstrated that the activity of VPGlu was involved in the regulation of heroin addiction and identified the VPGlu-LHb pathway as a potential intervention to reduce heroin seeking motivation.

A preliminary investigation of eye-tracking software to inform an ABA renewal mitigation procedure

ABA renewal is one type of operant renewal in which a target response is reinforced in a unique context (i.e., Context A), extinguished in novel context (i.e., Context B), and then recurs following a transition back to the original context. Recently, researchers have examined the robust phenomenon of ABA renewal when differential reinforcement of an alternative response is included in Context B and the renewal test. One method to mitigate ABA renewal is to program common stimuli so as to increase the similarity between Context A and Context B. This stimulus control strategy may support the generalization of behavior change between contexts. Currently, no studies exist on how to empirically derive the selection of the stimuli to program into Context B. We conducted a preliminary investigation using eye-tracking software to empirically determine which common stimulus to program into a three-phase ABA renewal arrangement that included differential reinforcement for 12 undergraduate students in a translational preparation. Our results replicate previous research demonstrating ABA renewal despite differential reinforcement contingencies. Further, ABA renewal may be less robust and more variable when common stimuli selected for programming are empirically determined using eye-tracking software.

Transition between habits and goal-directed actions in the renewal effect.

Three experiments with rats explored whether previously extinguished goal-directed and habitual responding recover with the same status using an ABA renewal preparation. In Experiments 1a and 1b, a lever-press response was minimally (four sessions) or extensively (16 sessions) trained in one context (Context A) and extinguished in another context (Context B). Then, outcome devaluation took place in either Context A or Context B in which a food pellet reinforcing the response was paired with lithium chloride (LiCl) for devalued groups and with saline for a control group. Finally, renewal of the extinguished response was tested in both Contexts A and B. We confirmed that both minimally and extensively trained responses renewed as goal-directed action regardless of the context in which devaluation took place. This finding was replicated in Experiment 2 even after more extended acquisition training (32 sessions). However, another group that received outcome devaluation before but not after extinction training showed habitual performance during extinction training as well as in a subsequent renewal test. Experiment 3 replicated these results and confirmed that renewal of goal direction for rats that received extinction training immediately prior to outcome devaluation was not an artifact of consecutive LiCl exposures over a short period of time in Experiments 1 and 2, using a more reliable devaluation protocol. Overall, the present results extend previous findings suggesting that actions and habits renew with the same status by returning to the original context after extinction. The most critical finding is the differential effects of pre- and postextinction devaluation on the expression of habitual behavior; extinction prior to devaluation may convert a habitual performance into a goal-directed action. This novel finding is discussed in relation to recent studies that identified several factors contributing to a transition from habitual to goal-directed control of instrumental behavior. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

ABA, ABC, and AAB renewal effects and individual differences of learning on fear conditioning using social stimuli

We examined whether ABA, ABC, and AAB renewal effects could be observed using fear conditioning with social stimuli as both conditioned stimulus (CS) and unconditioned stimulus (US) to investigate the possibility of relapse following exposure interventions for social anxiety in a laboratory setting. Sixty-four participants were randomly allocated to four groups (AAA, ABA, ABC, and AAB). They received nine pairings with a neutral face (CS) and aggressive facial expressions and insults (US) during the acquisition phase, and then received 18 pairings with the same CS and a neutral comment in the extinction phase. Following the extinction, the testing phase (three trials) was conducted. The background colors presented in each phase were manipulated to serve as the contextual stimuli. ANOVA showed the occurrence of the three types of renewals, but there were no consistent results showing differences between the renewals. Bayesian modeling demonstrated that there are some relationships between each parameter in the learning curves and social anxiety. The participants were non-clinical populations; therefore, it remains unclear whether the findings can be generalized to clinical populations. The results suggest that relapse following exposure therapy is related to a contextual change from the therapeutic environment and that individual differences in learning are related to social anxiety symptoms.

Partial reinforcement extinction and omission effects in the elimination and recovery of discriminated operant behavior.

Three experiments explored how training reinforcement schedules and context influence the elimination and recovery of human operant behavior. In Experiment 1, participants learned a discriminated operant response in Context A before the response was eliminated with extinction in Context B. They then received a final test in each context. Groups were trained with a discriminative stimulus that predicted a reinforced response on either every trial (continuous reinforcement [CRF]) or some of the trials (partial reinforcement [PRF]). Extinction was slower following PRF training (a partial reinforcement extinction effect [PREE]) and extinguished responding increased when tested in Context A ("ABA" renewal). Experiment 2 further confirmed the PREE was obtained equally whether extinction occurred in the training context (Context A) or a new context (Context B) which is consistent with trial-based accounts of the PREE. Experiment 3 used the same design as Experiment 1 to evaluate the influence of training reinforcement on response elimination with an omission contingency. Across the omission training phase in Context B, the decrease in responding occurred more slowly in the PRF-trained group in comparison to the CRF-trained group, perhaps the first demonstration of what might be termed a PRF omission effect. Again, ABA renewal was observed in Context A. Training reinforcement schedule therefore had a similar influence on response elimination with extinction and omission. Elimination and recovery of human instrumental behavior, with extinction or omission, are influenced by training reinforcement schedule and context. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Renewal of cocaine seeking using social and nonsocial contextual stimuli.

Various nonsocial cues have been used as stimuli to examine the contextual control of drug seeking behavior, but little is known about the role of social stimuli. This study determined if renewal of cocaine seeking is differentially controlled using a context consisting of either a social peer and/or house light illumination. In Experiment 1, male and female rats trained to self-administer cocaine in the presence of a same-sex social peer and house light illumination (context A). Following self-administration, rats were randomly assigned to either an AAA (control) or ABA (renewal) group for extinction. For AAA rats, extinction consisted of the same context A as self-administration; for ABA rats, extinction occurred without the peer or house light (context B). Following extinction, renewal of cocaine seeking occurred by testing the peer alone, house light alone, and the peer + house light combination. Experiment 2 was conducted to ensure that the house light alone was sufficiently salient to produce renewal. Both experiments showed that rats acquired cocaine self-administration and extinguished lever pressing. In Experiment 1, the ABA group renewed cocaine seeking to the peer and peer + house light, but not to the house light alone. In Experiment 2, ABA rats renewed cocaine seeking to the house light alone, indicating it was sufficiently salient to produce renewal. The AAA group did not show renewal in either experiment. Social peers serve as powerful stimuli that can overshadow nonsocial visual stimuli in the renewal of cocaine seeking.

ABA, AAB and ABC renewal with Pavlovian Conditioning of Tentacle Lowering procedure in the snail Cornu aspersum

This study assesses the recovery of the conditioned response (CR) due to a contextual change (renewal effect) in the Cornu aspersum, using the appetitive Pavlovian Conditioning of Tentacle Lowering procedure. Snails experienced an odorous conditioned stimulus (CS) paired with food (conditioning), followed by the exposition to the CS without any consequence (extinction). Then, they were exposed to the CS in a different context from the extinction one (renewal test). The contexts were three types of illumination. In Experiment 1a, the conditioning was performed in context A, the extinction was conducted in context B and the renewal test was performed in context A. For Experiment 1b, the conditioning and extinction were conducted in context A and renewal was performed in context B. In Experiment 1c, three dissimilar contexts were used for each experimental phase: context A for the conditioning, context B for the extinction and context C for the renewal. In Experiment 2, the renewal magnitude was compared among the three paradigms (ABA, AAB and ABC). Experiments 1a, 1b and 1c showed a recovery of the CR when subjects experienced a contextual change and Experiment 2 showed equivalent levels of renewal in the three paradigms. Learning processes and theories involved are discussed.

Prelimbic cortex inactivation prevents ABA renewal based on satiety state

We have previously shown that the rat prelimbic cortex (PL) is necessary for contexts to promote the performance of instrumental behaviors that have been learned in them, whether the context is physical (operant chamber) or behavioral (recent performance of a behavior that has historically preceded the target in a behavior chain). In the present experiment, we investigated the role of the PL in satiety level as an interoceptive acquisition context. Rats were trained to lever-press for sweet/fat pellets while sated (22 hrs continuous food access) followed by the extinction of the response while hungry (22 hrs food deprived). Pharmacological inactivation of the PL (with baclofen/muscimol infusion) attenuated renewal of the response that occurred upon a return to the sated context. In contrast, animals that received a vehicle (saline) infusion showed renewal of the previously extinguished response. These results support the hypothesis that the PL monitors the relevant contextual elements (physical, behavioral, or satiety state) associated with reinforcement of a response and promotes the subsequent performance of that response in their presence.

Operant ABA renewal during dense and lean schedules of differential reinforcement.

Renewal is a type of relapse that occurs due to a change in context. Previous research has demonstrated that renewal of target responding may occur despite the availability of differential reinforcement for an alternative response (DRA). Nevertheless, the current literature on renewal presents mixed findings regarding the effects of dense and lean schedules of DRA on the magnitude of renewal. We used a translational approach with undergraduate college students and a task on a touchscreen tablet device to study the effects of dense and lean schedules of DRA during repeated renewal tests. All participants experienced two, three-phase ABA renewal arrangements. In the dense and lean renewal arrangements, we differentially reinforced alternative behavior in Context B and the renewal test in Context A on a VI 3-s or a VI 12-s schedule, respectively. Overall, we observed renewal in 31/36 (86%) renewal tests regardless of the density of reinforcement for the alternative response. Furthermore, the results showed that although renewal occurred in both arrangements, we found slightly higher magnitudes of renewal during DRA with lean schedules of reinforcement relative to dense schedules. We discuss the implications of these findings as they relate to the treatment of problem behavior.

Optogenetic stimulation of infralimbic cortex projections to the paraventricular thalamus attenuates context-induced renewal.

Contexts associated with prior reinforcement can renew extinguished conditioned responding. The prelimbic (PL) and infralimbic (IL) cortices are thought to mediate the expression and suppression of conditioned responding, respectively. Evidence suggests that PL inputs to the paraventricular nucleus of the thalamus (PVT) drive the expression of cue-induced reinstatement of drug seeking and that IL inputs to the PVT mediate fear extinction retrieval. However, the role of these projections in renewal of appetitive Pavlovian conditioned responding is unknown. We trained male and female Long-Evans rats to associate a conditioned stimulus (CS; 10s white noise) with delivery of a 10% sucrose unconditioned stimulus (US; .2ml/CS) to a fluid port in a distinct context (Context A). We then extinguished responding by presenting the CS without the US in a different context (Context B). At test, rats were returned to Context A, and optogenetic stimulation was delivered to either the IL-to-PVT or PL-to-PVT pathway during CS presentations. Optically stimulating the IL-to-PVT, but not the PL-to-PVT pathway, attenuated ABA renewal of CS port entries, and this effect was similar in males and females. Further, rats self-administered optical stimulation of the IL-to-PVT but not the PL-to-PVT pathway suggesting that activation of the IL-to-PVT pathway is reinforcing. The effectiveness of optical stimulation parameters to activate neurons in the IL, PL and PVT was confirmed using Fos immunohistochemistry. These findings provide evidence for novel neural mechanisms in renewal of responding to a sucrose-predictive CS, as well as more generally in contextual processing and appetitive associative learning.