Gabrielle Weidemann

Opioid Receptors in the Midbrain Periaqueductal Gray Regulate Extinction of Pavlovian Fear Conditioning

Four experiments studied the role of opioid receptors in the midbrain periaqueductal gray matter (PAG), an important structure eliciting conditioned fear responses, in the extinction of Pavlovian fear. Rats received pairings of an auditory conditioned stimulus (CS) with a foot shock unconditioned stimulus (US). The freezing conditioned response (CR) elicited by the CS was then extinguished via nonreinforced presentations of the CS. Microinjection of the opioid receptor antagonist naloxone into the ventrolateral PAG (vlPAG) before nonrein-forced CS presentations impaired development of extinction, but such microinjections at the end of extinction did not reinstate an already extinguished freezing CR. This role for opioid receptors in fear extinction was specific to the vlPAG because infusions of naloxone into the dorsal PAG did not impair fear extinction. Finally, the impairment of fear extinction produced by vlPAG infusions of naloxone was dose-dependent. These results show for the first time that the midbrain PAG contributes to fear extinction and specifically identify a role for vlPAG opioid receptors in the acquisition but not the expression of such extinction. Taken together with our previous findings, we suggest that, during fear conditioning, activation of vlPAG opioid receptors contributes to detection of the discrepancy between the actual and expected outcome of the conditioning trial. vlPAG opioid receptors regulate the learning that accrues to the CS and other stimuli present on a trial because they instantiate an associative error correction process influencing US information reaching the site of CS-US convergence in the amygdala. During nonreinforcement, this vlPAG opioid receptor contribution signals extinction.

Blocking, unblocking, and overexpectation of fear: A role for opioid receptors in the regulation of Pavlovian association formation

Injection of the opioid receptor antagonist naloxone facilitated acquisition of fear to contextual and auditory conditioned stimuli (CSs) in Experiments 1A and 1B. Experiment 2 showed that prior conditioning to a distinctive context blocked conditioning to an auditory CS. Blocking of CS fear was prevented by administrations of naloxone or increases in footshock intensity. Blocking of CS fear was facilitated by decreases in footshock intensity in a naloxone-reversible manner. Experiment 3 showed that compound conditioning of two CSs, each previously and separately paired with shock, produced overexpectation of fear that was reversed by naloxone. These results are consistent with a role for opioid receptors controlling Pavlovian association formation by regulating the discrepancy (lambda - SigmaV) described by R. A. Rescorla and A. R. Wagner (1972).

Evidence for expectancy as a mediator of avoidance and anxiety in a laboratory model of human avoidance learning

A laboratory model was developed to study human avoidance learning. Participants could avoid an electric shock signalled by a 5-s conditioned stimulus (CS) by pressing one of a set of response buttons. Self-reported shock expectancy and skin conductance were recorded during a subsequent 10-s interval before shock. Shock expectancy declined when the correct avoidance response was learned and returned when the response was unavailable. Learning transferred to another shock CS. Parallel effects were observed on skin conductance once performance anxiety was controlled by requiring responding on all trials. Learning was faster when the Pavlovian contingencies were trained before introduction of the instrumental response. The results support a cognitive model of anxiety in which performance of an avoidance response reduces expectancy of an aversive outcome and thereby reduces anxiety.

Covariation of Alternative Measures of Responding in Rabbit (Oryctolagus cuniculus) Eyeblink Conditioning During Acquisition Training and Tone Generalization

The likelihood, size, and speed of eyelid movements are thought to covary during the acquisition and expression of conditioning in rabbits (Oryctolagus cuniculus) and are generally accepted as interchangeable measures of the associative strength activated by the conditioned stimulus (CS). To test this assumption, the authors examined the patterns of covariation in these eyelid movement measures in acquisition and stimulus generalization in the upper eyelid and nictitating membrane. Rather than the expected covariation among these measures, eyelid movement magnitudes during the CS were distributed in approximately a bimodal manner. That is, eyelid activity consisted largely of a mixture of very small (< 0.125 mm) baseline measurements and larger (> 1 mm) movements. The results are discussed with respect to their implications for real-time models of eyelid conditioning.

Savings in classical conditioning in the rabbit as a function of extended extinction

In the present experiments, savings phenomena following a limited amount of initial acquisition and extended extinction were examined. Experiments 1 and 2 compared rates of reacquisition following brief acquisition and various amounts of extinction in conditioning of the rabbit’s nictitating membrane and heart rate response, respectively. Experiment 3 compared rates of acquisition to a novel stimulus (e.g., light) following brief acquisition and various amounts of extinction to another stimulus (e.g., tone). In addition, in Experiment 3 recovery of responding to the extinguished stimulus during acquisition to the novel, cross-modal stimulus was examined. Experiments 1, 2, and 3 demonstrated that with a limited number of acquisition trials (1) there was a graded reduction in the rate of reacquisition as a function of the number of extinction trials in both conditioning preparations, (2) there was a graded reduction in the rate of cross-modal acquisition as a function of the number of extinction trials, but (3), in Experiment 3, recovery of responding to the extinguished stimulus during cross-modal training of the novel stimulus appeared uniformly robust even in the face of extended extinction.

Awareness is necessary for differential trace and delay eyeblink conditioning in humans

Squire et al. have proposed that trace and delay eyeblink conditioning procedures engage separate learning systems: a declarative hippocampal/cortical system associated with conscious contingency awareness, and a reflexive sub-cortical system independent of awareness, respectively (Clark and Squire, 1998; Smith et al., 2005). The only difference between these two procedures is that the conditioned stimulus (CS) and the unconditioned stimulus (US) overlap in delay conditioning, whereas there is a brief interval (e.g., 1s) between them in trace conditioning. In two experiments using the same procedure as Clark and Squires group, we observed differential conditioning only in participants who showed contingency awareness in a post-experimental questionnaire, with both trace and delay procedures. We interpret these results to suggest that, although there may be multiple brain regions involved in learning, these regions are organized as a coordinated system rather than as separate, independent systems.

Is Perruchet's Dissociation Between Eyeblink Conditioned Responding and Outcome Expectancy Evidence for Two Learning Systems?

P. Perruchet (1985b) showed a double dissociation of conditioned responses (CRs) and expectancy for an airpuff unconditioned stimulus (US) in a 50% partial reinforcement schedule in human eyeblink conditioning. In the Perruchet effect, participants show an increase in CRs and a concurrent decrease in expectancy for the airpuff across runs of reinforced trials; conversely, participants show a decrease in CRs and a concurrent increase in expectancy for the airpuff across runs of nonreinforced trials. Three eyeblink conditioning experiments investigated whether the linear trend in eyeblink CRs in the Perruchet effect is a result of changes in associative strength of the conditioned stimulus (CS), US sensitization, or learning the precise timing of the US. Experiments 1 and 2 demonstrated that the linear trend in eyeblink CRs is not the result of US sensitization. Experiment 3 showed that the linear trend in eyeblink CRs is present with both a fixed and a variable CS-US interval and so is not the result of learning the precise timing of the US. The results are difficult to reconcile with a single learning process model of associative learning in which expectancy mediates CRs.

Competition between an avoidance response and a safety signal: Evidence for a single learning system

Two experiments examined competition between an instrumental avoidance response and a Pavlovian safety signal for association with omission of electric shock in a human fear conditioning paradigm. Self-reported shock expectancies and skin conductance responses were consistent with blocking of learning of the instrumental contingency by prior training of the Pavlovian contingency, and vice versa. The results support the idea that a common learning mechanism underlies both Pavlovian and instrumental conditioning. The expectancy data suggest that this learning mechanism is cognitive in nature, and that Pavlovian and instrumental learning involve external and internal attributions, respectively. The procedure may thus serve as a laboratory model for attributional processes involved in the acquisition of threat expectancies in anxiety and anxiety disorders.

Apparatus Exposure Produces Profound Declines in Conditioned Nictitating-Membrane Responses to Discrete Conditioned Stimuli by the Rabbit (Oryctolagus cuniculus)

The present experiments demonstrated that in the rabbit (Oryctolagus cuniculus) nictitacing-membrane (NM) preparation, exposure to the experimental apparatus produces profound declines in conditioned responding to a discrete conditioned stimulus (CS; Experiments 1, 2A, and 3). Moreover, this decremental effect is at most attenuated in only a minor way when the unconditioned stimulus (US) is presented during exposure to the apparatus (Experiment 2B). Controls for retention loss (Experiments 1 and 3) and for handling and placement in a different context (Experiment 3) did not produce significant declines in responding. These findings challenge theories of extinction that rely primarily on context-US associations but are more consistent with theories that assume context-CS-US associations.

Do Reaction Times in the Perruchet Effect Reflect Variations in the Strength of an Associative Link

In 3 experiments, we examined Perruchet, Cleeremans, and Destrebecqzs (2006) double dissociation of cued reaction time (RT) and target expectancy. In this design, participants receive a tone on every trial and are required to respond as quickly as possible to a square presented on 50% of those trials (a partial reinforcement schedule). Participants are faster to respond to the square following many recent tone-square pairings and slower to respond following many tone-alone presentations. Of importance, expectancy of the square is highest when performance on the RT task is poorest-following many tone-alone trials. This finding suggests that RT performance is determined by the strength of a tone-square link and that this link is the product of a non-expectancy-based learning mechanism. The present experiments, however, provide evidence that the speeded RTs are not the consequence of the strengthening and weakening of a tone-square link. Thus, the RT Perruchet effect does not provide evidence for a non-expectancy-based link-formation mechanism.