Four experiments were performed to explore the role of context in operant extinction. In all experiments, leverpressing in rats was first reinforced with food pellets on a variable interval 30-s schedule, then extinguished, and finally tested in the same and a different physical context. The experiments demonstrated a clear ABA renewal effect, a recovery of extinguished responding when conditioning, extinction, and testing occurred in contexts A, B, and A, respectively. They also demonstrated ABC renewal (where conditioning extinction and testing occurred in contexts A, B, and C) and, for the first time in operant conditioning, AAB renewal (where conditioning, extinction, and testing occurred in contexts A, A, and B). The latter two phenomena indicate that tests outside the extinction context are sufficient to cause a recovery of extinguished operant behavior and, thus, that operant extinction, like Pavlovian extinction, is relatively specific to the context in which it is learned. AAB renewal was not weakened by tripling the amount of extinction training. ABA renewal was stronger than AAB, but not merely because of context A's direct association with the reinforcer.

D-cycloserine (DCS) may facilitate fear extinction learning, but the behavioral consequences and mechanisms behind this effect are not well understood at present. In this article, we re-analyze data from previously-reported null-result experiments and find that rats showing above-median extinction learning during DCS treatment benefited from the drug, whereas rats showing below-median (and in this case little) extinction learning did not. Two additional experiments found that DCS facilitated extinction learning when specifically combined with a moderate, but not a small, number of extinction trials. DCS thus facilitates extinction learning only if the behavioral procedure first engages the extinction learning process. The benefits of the drug, however, were specific to the context in which extinction was learned-i.e., DCS did not prevent or influence the renewal of fear observed when the extinguished cue was tested in the original conditioning context.

Three experiments demonstrated, and examined the mechanisms that underlie, the renewal of extinguished discriminated operant behavior. In Experiment 1, rats were trained to perform one response (lever press or chain pull) in the presence of one discriminative stimulus (S; light or tone) in Context A, and to perform the other response in the presence of the other S in Context B. Next, each of the original S/response combinations was extinguished in the alternate context. When the S/response combinations were tested back in the context in which they had been trained, responding in the presence of S returned (an ABA renewal effect was observed). This renewal could not be due to differential context-reinforcer associations, suggesting instead that the extinction context inhibits either the response and/or the effectiveness of the S. Consistent with the latter mechanism, in Experiment 2, ABA renewal was still observed when both the extinction and renewal contexts inhibited the same response. However, in Experiment 3, previous extinction of the response in the renewing context (occasioned by a different S) reduced AAB renewal more than did extinction of the different response. Taken together, the results suggest at least two mechanisms of renewal after instrumental extinction. First, extinction performance is at least partly controlled by a direct inhibitory association that is formed between the context and the response. Second, in the discriminated operant procedure, extinction performance can sometimes be partly controlled by a reduction in the effectiveness of the S in the extinction context. Renewal of discriminated operant behavior can be produced by a release from either of these forms of inhibition.

This article reviews research on the behavioral and neural mechanisms of extinction as it is represented in both Pavlovian and instrumental learning. In Pavlovian extinction, repeated presentation of a signal without its reinforcer weakens behavior evoked by the signal; in instrumental extinction, repeated occurrence of a voluntary action without its reinforcer weakens the strength of the action. In either case, contemporary research at both the behavioral and neural levels of analysis has been guided by a set of extinction principles that were first generated by research conducted at the behavioral level. The review discusses these principles and illustrates how they have informed the study of both Pavlovian and instrumental extinction. It shows that behavioral and neurobiological research efforts have been tightly linked and that their results are readily integrated. Pavlovian and instrumental extinction are also controlled by compatible behavioral and neural processes. Since many behavioral effects observed in extinction can be multiply determined, we suggest that the current close connection between behavioral-level and neural-level analyses will need to continue.

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Female pelvic floor dysfunction (FPFD) is a complex group of conditions that include urinary incontinence and pelvic organ prolapse (POP). In humans, elastin homeostasis has been implicated in the pathophysiology of FPFD. Lysyl oxidase-like 1 knockout (LOXL1-KO) mice demonstrate abnormal elastic fiber homeostasis and develop FPFD after parturition. We compared the lower urogenital tract (LUT) anatomy and function in LOXL1-KO mice with and without POP. LUT anatomy was assessed in LOXL1-KO mice over 28 wk. Pelvic visceral anatomy in LOXL1-KO was evaluated with a 7-Tesla magnetic resonance imaging (MRI) scanner. LUT function was assessed using conscious cystometry and leak point pressure (LPP) testing. Quantitative histological analysis of elastic fibers was performed on external urethral sphincter (EUS) cross sections. By 25 wk of age, 50% of parous LOXL1-KO mice developed POP. LOXL1-KO mice with POP had greater variability in the size and location of the bladder on MRI compared with mice without POP. Parity and POP were associated with lower LPP. Elastin clusters were significantly increased in the EUS of LOXL1-KO mice with POP. Because parity triggers POP in LOXL1-KO mice, LOXL1-KO mice with POP have variable internal pelvic anatomy, and both parity and POP are associated with a decrease in LPP, we conclude that LOXL1 LUT anatomical and functional phenotype resembles FPFD in humans. The increase in elastin clusters in the urethra of LOXL1-KO mice with POP suggests that elastin disorganization may lead to functional abnormalities. We conclude that LOXL1 warrants further investigation in the pathphysiology of FPFD.

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The effects of obesity and type 2 diabetes (DMII) on the lower urinary tract (LUT) were characterized by evaluating voiding function and anatomy in female Zucker diabetic fatty (ZDF) rats. Age-matched female virgin rats were separated into three experimental groups: Zucker lean rats (control; normal diet, n = 22), ZDF rats (obese+nondiabetic; low-fat diet, n = 22), and ZDF rats (obese+diabetic; high-fat diet, n = 20). Rats were placed on their specified diet for 10 wk before urodynamic LUT evaluation. A suprapubic catheter was implanted 2 days before urodynamic studies. Voiding function was evaluated by cystometric and leak point pressure (LPP) testing. The bladder, urethra, and vagina were immediately excised for qualitative histological evaluation. Compared with control rats, obese+nondiabetic and obese+diabetic rats had significantly decreased contraction pressure ( P = 0.003) and increased cystometric filling volume ( P < 0.001). Both obese groups exhibited significantly higher voided volumes ( P = 0.003), less frequent urinary events ( P < 0.001), and increased residual volumes ( P = 0.039). LPP studies showed a nonsignificant decrease in LPP ( P = 0.075) and baseline pressure ( P = 0.168) in both obese groups compared with control. Histology of the external urethral sphincter in obese rats showed increased fibrosis, leading to disruption of the skeletal muscle structure compared with control. Additionally, the bladder wall of the obese+nondiabetic and obese+diabetic rats demonstrated edema and vasculopathy. Voiding dysfunction was evident in both obese groups but with no significant differences due to DMII, suggesting that voiding dysfunction in DMII may be attributable at least in part to chronic obesity.