Blockade of GABAA receptors in the interpositus nucleus modulates expression of conditioned excitation but not conditioned inhibition of the eyeblink response

The cerebellum and related brainstem structures are essential for excitatory eyeblink conditioning. Recent evidence indicates that the cerebellar interpositus and lateral pontine nuclei may also play critical roles in conditioned inhibition (CI) of the eyeblink response. The current study examined the role of GABAergic inhibition of the interpositus nucleus in retention of CI. Male Long-Evans rats were implanted with a cannula positioned just above or in the anterior interpositus nucleus before training. The rats were trained with two different tones and a light as conditioned stimuli, and a periorbital shock as the unconditioned stimulus. CI training consisted of four phases: 1) excitatory conditioning (8 kHz tone paired with shock); 2) feature-negative discrimination (2 kHz tone paired with shock or 2 kHz tone concurrent with light); 3) summation test (8 kHz tone or 8 kHz tone concurrent with light); and 4) retardation test (light paired with shock) After reaching a criterion level of performance on the feature-negative discrimination (40% discrimination), 0.5 μl picrotoxin (a GABA_A receptor antagonist) was infused at one of four concentrations, each concentration infused during separte test sessions. Picrotoxin transiently impaired conditioned responses during trials with the excitatory stimulus (tone) in a dose-dependent manner, but did not significantly impact responding to the inhibitory compound stimulus (tone-light). The results suggest that expression of conditioned inhibition of the eyeblink conditioned response does not require GABAergic inhibition of neurons in the anterior interpositus nucleus.     

Blockade of GABAA Receptors in the Interpositus Nucleus Modulates Expression of Conditioned Excitation but not Conditioned Inhibition of the Eyeblink Response

The cerebellum and related brainstem structures are essential for excitatory eyeblink conditioning. Recent evidence indicates that the cerebellar interpositus and lateral pontine nuclei may also play critical roles in conditioned inhibition (CI) of the eyeblink response. The current study examined the role of GABAergic inhibition of the interpositus nucleus in retention of CI. Male Long-Evans rats were implanted with a cannula positioned just above or in the anterior interpositus nucleus before training. The rats were trained with two different tones and a light as conditioned stimuli, and a periorbital shock as the unconditioned stimulus. CI training consisted of four phases: 1) excitatory conditioning (8 kHz tone paired with shock); 2) feature-negative discrimination (2 kHz tone paired with shock or 2 kHz tone concurrent with light); 3) summation test (8 kHz tone or 8 kHz tone concurrent with light); and 4) retardation test (light paired with shock). After reaching a criterion level of performance on the feature-negative discrimination (40% discrimination), 0.5 microl picrotoxin (a GABAA receptor antagonist) was infused at one of four concentrations, each concentration infused during separate test sessions. Picrotoxin transiently impaired conditioned responses during trials with the excitatory stimulus (tone) in a dose-dependent manner, but did not significantly impact responding to the inhibitory compound stimulus (tone-light). The results suggest that expression of conditioned inhibition of the eyeblink conditioned response does not require GABAergic inhibition of neurons in the anterior interpositus nucleus.     

Conditioning across the duration of a backward conditioned stimulus

Five conditioned suppression experiments examined the extent to which an appetitively motivated lever-press response can be punished by different components of a backward conditioned stimulus (CS). Using a 0-s unconditioned stimulus (US)-CS interval, Experiments 1 and 2 showed that the initial 3 s of a normally 30-s backward CS served as a more effective punisher than the CS as a whole. Experiment 3 found no such effect if the US-CS interval were 3 s rather than 0 s. Experiments 4A and 4B found that if the US-CS interval were 0 s, the initial part of the backward CS acquired excitatory properties although the CS as a whole passed a summation test for conditioned inhibition. By contrast, the 3-s US-CS interval supported inhibitory conditioning across the whole duration of the backward CS. Taken together, these findings support a modified version of Wagner's sometimes opponent process model, which suggests that different components of a backward CS become either excitatory or inhibitory depending on the components' temporal proximity to the US.     

Effects of ageing on visual discrimination learning in Drosophila melanogaster

Two experiments examined conditioned suppression of the Proboscis Extension Response (PER), unconditionally released by sucrose stimulation of gustatory tarsal receptors, in young (7-day-old), middle-aged (30-day-old) and old (50-day-old) Drosophila melanogaster males, reared at 25°C. Individual flies were trained in a differential conditioning procedure in which a white stimulus signalled a quinine reinforcer, whereas a black stimulus was non-reinforced. When trained from the outset with the discriminative procedure, flies of all ages acquired the discrimination, although the acquisition of PER suppression to the white stimulus was retarded in middle-aged and old flies. The retardation of the acquisition of PER suppression in middle-aged and old flies was replicated in a second study in which the flies received simple conditioning to the white stimulus prior to discrimination training.     

Contextual Control of Latent Inhibition by the Reinforcer

Three experiments examined the contextual control of latent inhibition (LI) by the unconditioned stimulus (US) using a within-subjects conditioned suppression procedure with rats. The effect of reducing the context change produced by the introduction of the shock US was investigated by presenting this US during preexposure to the conditioned stimulus (CS). Although limited CS preexposure in the absence of the US had no impact on subsequent conditioning, preexposure in the presence of the shock retarded both excitatory and inhibitory conditioning. We conclude that the introduction of the US during the conditioning phase of a normal LI experiment can produce a contextual change that reduces the observed magnitude of LI.     

Summation of excitatory and inhibitory control produced by traditional tone-shock contingencies and autocontingencies

Previous research has demonstrated that rats can use unsignaled shock to predict subsequent periods free from shock. This shock-no shock stimulus arrangement, termed an autocontingency, has appeared less likely to exert behavioral control when a traditional tone-shock contingency was simultaneously available. The present research examined the generality of CS-US contingency dominance in a conditioned suppression paradigm by using a summation test in which “probe” stimuli derived from tone-shock contingencies were superimposed upon responding maintained by an autocontingency. In experiment 1, an inhibitory CS accelerated responding only when responding was normally suppressed by the autocontingency. In experiment 2, an excitatory CS failed to yield conditioned suppression during an inhibitory (accelerative) period produced by the autocontingency. Unlike our previous findings (e.g., Davis, Memmott & Hurwitz, 1975), these results do not support a general notion of tone-shock contingency dominance over autocontingencies. Behavioral control by autocontingencies appears robust and “holds its own” in summation with both excitatory and inhibitory CSs derived from traditional contingencies.     

Some types of conditioned inhibitors carry collateral excitatory associations

Two experiments using summation tests in conditioned suppression with rats examined whether conditioned inhibitors generated by five different conditioning procedures have an associative structure which includes collateral excitatory associations. The existence of collateral conditioned excitation was inferred from an increase in the amount of manifest conditioned inhibition after a conditioned inhibitory stimulus (CS-) extinction treatment. The five CS-s evaluated were differential, explicitly unpaired, conditional, backward, and trace. With abbreviated conditioning (Experiment 1), the differential and explicitly unpaired CS-s exhibited conditioned inhibitory properties; the conditional, backward, and trace CS-s did not. Repeated extinction presentations of the CS- in the absence of the unconditioned stimulus unmasked conditioned inhibition to the conditional, backward, and trace CS-s revealing moderate degrees of conditioned inhibition for all five CS-s. After more extensive conditioning (Experiment 2), the explicitly unpaired and conditional CS-s were strongly inhibitory and the differential and trace CS-s were moderately inhibitory. The backward CS- was not inhibitory. Repeated presentations of the CS- in extinction unmasked conditioned inhibition to trace and backward CS-s. All five CS-s were now nearly equally inhibitory. That the measured inhibitory power of backward, trace, and conditional (after few trials) CS-s can be modulated by a CS- extinction treatment suggests that they have similar associative structures and carry, in addition to inhibitory associations, collateral excitatory associations that mask the expression of conditioned inhibition.     

Conditioned Inhibition Produced by Extinction of a Conditioned Stimulus

Four experiments used a conditioned taste aversion procedure to examine the potential for CS-alone extinction treatment to produce a conditioned stimulus that possesses inhibitory properties. In Experiment 1, saccharin was paired with LiCl, and then saccharin was presented alone for several trials to produce extensive behavioral extinction. Animals receiving this treatment were retarded in reacquiring conditioned responding to saccharin relative to control subjects receiving conditioning to the flavor for the first time. In Experiment 2, the extinguished saccharin stimulus was shown to decrease conditioned responding to a known excitor when the two stimuli were presented in compound as a summation test. Experiments 3A and 3B replicated the findings of Experiments 1 and 2 while providing evidence that the effects were not due to the differential effects of neophobia during testing. These three experiments revealed that an extinguished conditioned excitor passes retardation and summation tests for conditioned inhibition. Experiment 4 found that extinction of a known excitor was slowed when the excitor was extinguished in compound with a previously extinguished conditioned stimulus. That is, an extinguished CS provided protection from extinction to another CS, a finding also consistent with the view that extinction produces conditioned inhibition.     

The effects of electroconvulsive shock on the action of a reinforcing stimulus

Three experiments sought to evaluate the effect of electroconvulsive shock on the action of a reinforcing stimulus. In all experiments behavior was maintained on a 2 min variable interval schedule for food reinforcement. Foot shock at the termination of a buzzer stimulus served as the reinforcing stimulus for conditioned suppression during the ensuing buzzer interval. Omission of foot shock at the termination of the buzzer stimulus was followed by normal responding (no conditioned suppression) during the next buzzer interval. In Exp I electroconvulsive shock followed foot shock at varying time intervals. In the first subsidiary experiment electroconvulsive shock followed an unreinforced buzzer stimulus at varying time intervals. In the second subsidiary experiment electroconvulsive shock followed foot shock at varying time intervals and an additional buzzer stimulus was sounded between the termination of foot shock and the onset of electroconvulsive shock. These three experiments demonstrated that electroconvulsive shock invariably abolished the effects of the reinforcing stimulus if it followed conditioning by no more than 10.0 sec and never had an effect if it followed conditioning by 12.5 sec or more; electroconvulsive shock was not acting as a reinforcing stimulus in this situation.     

Associative structure of differential inhibition: implications for models of conditioned inhibition

Following A+/X- training (with A, X, and + being a light, tone, and footshock, respectively), rats received extinction of A and the training context, extinction of the training context alone, or no extinction. The inhibitory potential of X was then assessed with conditioned lick suppression in a neutral context using both summation and retardation tests. Extinction of the training context alone and extinction of A and the training context reduced the inhibitory potential of X appreciably and equally. Hence, what is traditionally called differential inhibition appears to depend not on the excitatory value of A but on the excitatory value of the training context. In conjunction with what is known about other inhibitory training procedures, these results suggest that a conditioned inhibitor is a stimulus that has been paired with little or no reinforcement in the presence of an accompanying stimulus that predicts greater reinforcement.     

Mechanisms underlying retarded emergence of conditioned responding following inhibitory training: evidence for the comparator hypothesis

The comparator hypothesis posits that conditioned responding is determined by a comparison at the time of testing between the associative strengths of the conditioned stimulus (CS) and stimuli proximal to the CS at the time of conditioning. The hypothesis treats all associations as being excitatory and treats conditioned inhibition as the behavioral consequence of a CS that is less excitatory than its comparator stimuli. Conditioned lick suppression by rats was used to differentiate four possible sources of retarded responding to an inhibitory CS. These include habituation to the unconditioned stimulus (US), latent inhibition to the CS, blocking of the CS-US association by the conditioning context, and enhanced excitatory associations to the comparator stimuli. Prior research has demonstrated the first three phenomena. Therefore, we employed parameters expected to highlight the fourth one--the comparator process. In Experiment 1, our negative contingency training was shown to produce a conditioned inhibitor that passed inhibitory summation and retardation tests. In Experiment 2 we found transfer of retardation from an inhibitory CS to a novel stimulus when the location where retardation-test training occurred was excitatory, which is indicative of contextual blocking and/or comparator effects. In Experiment 3, extinction of the conditioning context was found to attenuate retardation regardless of whether extinction occurred before or after the CS-US pairings of the retardation test. This indicates that much of the present retardation was due to the comparator process rather than to contextual blocking. Experiment 4 demonstrated that habituation to the US did not contribute to retardation in the present case. Collectively, these studies suggest that retardation following inhibitory training can be explained without recourse to any of the traditional mechanisms of conditioned inhibition.     

Conditioned suppression, punishment, and aversion

Three experiments were conducted to assess the aversive properties of a visual stimulus in the presence of which one group of birds received response-contingent shock (discriminated punishment) while a yoked group of birds received non-contingent shocks (conditioned suppression). In Experiment 1, presentation of the visual stimulus contingent on key pecking reduced the response rate (conditioned punishment effect) for birds under the conditioned suppression procedure but did not reduce the response rate of birds under the discriminative punishment procedure. Non-contingent shocks also produced greater suppression of responding maintained by positive reinforcement in the presence of a visual stimulus than did response-contingent shocks. In Experiment 2, a greater shock intensity (2 mA) was used. All the differences between the two groups found in Experiment 1 were also found in Experiment 2. Experiment 3 demonstrated that response-contingent shock did not result in a conditioned punishment effect even when positive reinforcers were unavailable during the discriminative punishment schedule. The exteroceptive stimulus that was paired with shock in the conditioned suppression procedure acquired the ability to punish behavior. The exteroceptive stimulus in the discriminative punishment schedule did not acquire this ability.     

Predictive learning in nutrient-based flavor conditioning

This paper presents two experiments on nutrient-based flavor conditioning with rats as subjects and sucrose as the unconditioned stimulus (US). Experiment 1 was aimed at establishing an optimal control for conditioning, comparing simultaneous and serial presentations of a flavor and the US. The results showed that simultaneous, but not serial training, produced conditioning. Experiment 2 was designed to obtain evidence of summation as an index of both conditioned inhibition and predictive learning. Group Simultaneous received Pavlovian conditioned inhibition training during which flavor A was simultaneously paired with sucrose on excitatory trials (A+), and forming an unreinforced compound with flavor B on inhibitory trials (AB-). An independent excitor for the summation test was also trained by simultaneous pairings with sucrose (C+). In the control group (Blocked), the AB- trials were presented forming a block at the beginning of training to avoid a negative contingency-relationship with sucrose, and flavor A received serial rather than simultaneous pairing with sucrose (A --> +). On the summation test, only in group Simultaneous was consumption of the CB compound lower than that of flavor C alone, suggesting that, during training, flavor A activated an expectancy of the US occurrence.     

Enhancement of Pavlovian conditioned inhibition achieved by posttraining inflation of the training excitor

In two conditioned lick suppression experiments using water-deprived rats, we examined the effects of following Pavlovian conditioned inhibition training (i.e., A–US/AX-NoUS) with pairings of the training excitor (A) and the unconditioned stimulus (US). Experiments 1 and 2 assessed the effects of this posttraining inflation treatment on Pavlovian conditioned inhibition using a summation test and a retardation test, respectively. Both experiments revealed that subjects exposed to inflation treatment demonstrated behavior indicative of enhanced conditioned inhibition compared to subjects that did not receive inflation treatment. The results in conjunction with other recent findings suggest that posttraining associative deflation (i.e., extinction of A) and inflation effects are more symmetrical than has previously been realized.     

Conditioned inhibition of fear: Evidence for a competing response mechanism

In two experiments, inhibitory conditioning was attempted by presenting a discrete CS in a neutral stimulus environment shortly following the termination of either shock (Experiment 1) or a second discrete CS which had been paired in a forward manner with shock (Experiment 2). Evidence of successful inhibitory conditioning was mixed in Experiment 1, where the properties of the CS were assessed within an escape-from-fear procedure. Postresponse presentations of the CS enhanced performance, whereas the presentation of the CS prior to responding did not have the expected degrading effect on performance. In Experiment 2, the inhibitory properties of the CS were assessed by combining this stimulus with an excitatory CS and presenting the compound to rats engaged in a water-reinforced licking response. Less response suppression was found in reaction to this compound relative to three separate comparison conditions, thus witnessing the success of the inhibitory-conditioning procedure used. The common assumption that inhibitory conditioning results from the nonreinforcement of a CS in a situation where reinforcement is expected, i.e., one which contains previously reinforced cues, is not supported by these data, for no previously reinforced cues were simultaneously presented with the CS during inhibitory training. The data are in agreement with a conditioned antagonistic-response interpretation of inhibitory conditioning.     

Analysis of the pavlovian properties of signals for punishment

Rats learned to suppress lever pressing in the presence of a compound stimulus that signalled either response-independent shock (conditioned suppression) or response-dependent shock (punishment). Suppression to one element of this compound was blocked if the other element had previously signalled the same contingency as that holding in the presence of the compound. Two experiments, however, failed to find significant evidence of blocking if the pretrained element had signalled conditioned suppression and the compound signalled a punishment contingency. On the other hand, if one stimulus signalled punishment of one response it was able to block the acquisition of control by the second stimulus when the compound signalled punishment of a different response. Finally, although animals showed no suppression to one element of a compound signalling conditioned suppression if the other had previously signalled punishment, this apparent blocking effect concealed that what they learned was that the added element signalled the cancellation of the instrumental contingency. These results provide little support for the view that stimuli signalling punishment contingencies suppress responding in whole or in part by virtue of their Pavlovian relation to shock.     

Preconditioning exposure to the unconditined stimulus affects the acquisition of a conditioned emotional response

Four experiments examined the UCS preexposure phenomenon using conditioned suppression of food-reinforced responding as a measure of excitatory conditioning, and electric shock as a UCS. In Experiment 1, groups of rats were preexposed to unsignaled 0.8-mA electric shocks for 0, 1, 3, 5, or 10 days, and then conditioned with a 0.8-mA electric shock. Preexposure to electric shock 1 day prior to conditioning enhanced the acquisition of a CER, whereas preexposure to electric shock for 3, 5, or 10 days prior to conditioning attenuated the acquisition of a CER as a direct function of the number of days of preexposure. In Experiments 2 and 2A, groups of rats were preexposed to unsignaled electric shocks of 0.3, 0.5, 0.8, or 1.3 mA for 10 days, and then conditioned with a 0.8-mA electric shocl. All groups preexposed to electric shock acquired the CER at a slower rate than a group not preexposed to electric shock. The greatest attenuation of CER conditioning occurred when the same intensity electric shock was used during both the preexposure and conditioning phases. In Experiment 3, groups of rats were preexposed to signaled electric shocks of either 0.5, 0.8, or 1.3 mA, and then conditioned with a 0.8-mA electric shock. All groups preexposed to electric shock acquired the CER at a slower rate than a group not preexposed to electric shock. As in Experiments 2 and 2A, the greatest attenuation of CER conditioning occurred when the same intensity electric shock was used during both the preexposure and conditioning phases. In Experiment 4, groups of rats were preexposed to series of 0.5, 0.8, or 1.3-mA electric shocks which they could escape by performing a chain-pull response. Rats in each of these groups had yoked partners which received the same number, intensity, and temporal pattern of electric shocks, but could not perform a response to escape shock. All groups were then conditioned with a 0.8-mA electric shock. Rats preexposed to escapable electric shocks showed equal or greater attenuation of CER conditioning than rats which could not escape shock during the preexposure phase. These results are discussed in terms of nonassociative and associative explanations of the UCS preexposure phenomenon.     

Locus of the effect of a surprising reinforcer in the attenuation of blocking

Previous experiments on conditioned suppression in rats have shown that prior conditioning to one element of a compound conditioned stimulus paired with shock may block or prevent conditioning to the other element. Reliable conditioning may, however, occur to the added element (blocking may be attenuated), if a surprising second shock is added shortly after each compound trial. Experiment I confirmed this finding, and further showed that blocking was attenuated only when the second shock occurred 10 s after the compound trial, not when it occurred 100 s later. Experiment II showed that the surprising omission of an expected second shock 10 s after each compound trial would also attenuate blocking, thus implying that the surprising event does not itself act to reinforce conditioning to the added element, but rather permits the unconditioned stimulus (the first shock) to play its normal role as an effective reinforcer. This conclusion was confirmed by Experiment III, which showed that a surprising second shock does not produce any increase in conditioning to the added element on the trial on which it occurs; rather it serves to ensure adequate conditioning to that element on a subsequent compound trial. The implication is that the surprising event acts proactively to prevent subjects learning to ignore an otherwise redundant stimulus.     

The comparator hypothesis of conditioned response generation: manifest conditioned excitation and inhibition as a function of relative excitatory strengths of CS and conditioning context at the time of testing

In the present research water-deprived rats were used in a conditioned lick suppression paradigm to test and further develop Rescorla's (1968) contingency theory, which posits that excitatory associations are formed when a conditioned stimulus (CS) signals an increase in unconditioned stimulus (US) likelihood and that inhibitory associations develop when the CS signals a decrease in US likelihood. In Experiment 1 we found that responding to a CS varied inversely with the associative status of the context in which the CS was trained and that this response was unaltered when testing occurred in a distinctively dissimilar context with a different conditioning history, provided associative summation with the test context was minimized. These results suggest that manifest excitatory and inhibitory conditioned responding is modulated by the associative value of the training context rather than that of the test context. In Experiment 2 it was demonstrated that postconditioning decreases in the associative value of the CS training context reduced the effective inhibitory value of the CS even when testing occurred outside of the training context. Moreover, this contextual deflation effect was specific to the CS training context as opposed to any other excitatory context. Collectively, these studies support the comparator hypothesis, which states that conditioned responding is determined by a comparison of the associative strengths of the CS and its training context that occurs at the time of testing rather than at the time of conditioning. This implies that all associations are excitatory and that responding indicative of conditioned inhibition reflects a CS-US association that is below (or near) the associative strength of its comparator stimulus. It is suggested that response rules which go beyond a monotonic relation between associative value and response strength can partially relieve learning theories of their explanatory burdens, thereby allowing for simpler models of acquisition.     

The Relation of the Galvanic Skin Reflex Recovery Curve to Reactivity,Resistance Level,and Perspiration

The effect of stimulus compounding in classical conditioning was investigated by conditioning one group of rats to a compound CS consisting of a buzzer and light and then conditioning separate groups of rats to the individual elements of the compound CS. On hurdle-jump test trials, the group of Ss conditioned to the compound CS performed better than Ss conditioned to the elements of the compound. Strength of conditioning to each of the elements of the compound CS was about equal. There was some evidence of a summation effect resulting from conditioning to the compound CS. Strength of conditioning to the compound CS was somewhat greater than the sum of the response strengths conditioned to the elements of the compound CS.