Classical conditioning after cerebellar lesions in humans.

Explored classical conditioning in human Ss who had lesions in their cerebellar circuitry. Seven patients with damage to cerebellar structures and matched control Ss underwent simple delay tone–airpuff conditioning. Eyelid CR acquisition was severely disrupted in the patient group, whereas autonomic CRs and slow cortical potentials developing between the CS and the unconditioned stimulus/stimuli (UCS) were unaffected. Results are consistent with animal studies and earlier case reports indicating that intact cerebellar structures are necessary for the acquisition of classically conditioned motor responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of the middle cerebellar peduncle disrupt acquisition and retention of the rabbit's classically conditioned nictitating membrane response.

Rabbits were classically conditioned to emit a nictitating membrane response (NMR) to either a light or tone conditioned stimulus (CS) paired with an eye shock unconditioned stimulus (UCS). They then received lesions of the middle cerebellar peduncle (MCP) or served as unoperated controls. Following surgery, they were given separate presentations of tone, light, and vibratory CSs, each paired with the eye shock UCS. In this way, conditioned responses (CR) to the previously trained light or tone served as a test of retention, whereas CRs to the remaining two conditioned stimuli (tone and vibratory or light and vibratory) served as a test of acquisition. The results of the study revealed that rabbits with complete lesions of the MCP showed disrupted acquisition and retention of the conditioned NMR to all stimuli, rabbits with partial MCP lesions also showed disrupted acquisition and retention to all CSs, but to a lesser degree, and animals with lesions that missed the MCP and unoperated controls both showed normal acquisition and retention of the conditioned NMR. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interpositus lesion abolition of the eyeblink conditioned response is not due to effects on performance.

Classical conditioning of the rabbit eyeblink response was used to study the effects of cerebellar lesions on performance in animals trained with low-intensity unconditioned stimuli (UCS). Animals were trained with 1 or 2 low-intensity corneal-airpuff UCSs paired with a tone-conditioned stimulus. This study confirms earlier findings demonstrating the differential effects of lesions of deep cerebellar nuclei on the conditioned and unconditioned responses (CRs and UCRs). Lesions of the anterior interpositus nucleus of the cerebellum in animals that were successfully conditioned abolished CRs without affecting UCR performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Disrupted eyelid conditioning in a patient with damage to cerebellar afferents.

A 54-year-old woman with damage to cerebellar circuitry resulting from a cerebrovascular accident underwent classical conditioning of the eye-blink response to a tone conditioned stimulus (CS) and an air-puff unconditioned stimulus (UCS). In contrast to 5 age-matched controls who readily acquired the conditioned response (CR), emitting a mean of 56.7 CRs over 70 trials, the patient emitted only 6 CRs in 100 trials and never emitted 2 consecutive CRs. There were no differences in spontaneous blink rate, sensitivity to the air puff, or sensitivity to the tone between the experimental subject and the control subjects. That conditioning of the eye-blink response is disrupted in a human with damage to cerebellar circuitry is consistent with an accumulating body of literature indicating that the cerebellum is the essential site of plasticity for classically conditioned somatic responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Autonomic-somatic interaction and hippocampal theta activity.

In 2 experiments, a total of 16 New Zealand rabbits were given extended differential classical conditioning training in which tones served as conditioned stimuli (CS) and shock to the eye served as the unconditioned stimulus (UCS). Corneo-retinal potential (CRP), heart rate (HR), and hippocampal EEG conditioned responses were measured. Changes in general somatic activity were also assessed. HR decelerations were associated with early stages of CRP discrimination, whereas HR accelerations and relatively more somatomotor activity were associated with later acquisition. These findings suggest that HR accelerations, associated with asymptotic CRP responding, are mediated via somatomotor changes. Although relatively more hippocampal theta activity was associated with later stages of conditioning, when somatomotor increases occurred theta was also prominent throughout acquisition. This finding suggests that either arousal properties of the CR are instrumental in producing theta or it is correlated with the associative properties of CS-UCS contingencies. (15 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lateral septal lesions enhance conditioned bradycardia in the rabbit.

52 New Zealand albino rabbits received sham lesions or complete, medial, lateral, or posterior septal lesions and were subjected to differential conditioning in which tones of different frequencies served as CSs, and paraorbital electric shock was the UCS. EMG, heart rate (HR), blood pressure (BP) CRs, and hippocampal rhythmic slow wave activity (RSA) were recorded. Lateral or complete septal lesions enhanced the bradycardiac HR CR but had no effect on the BP depressor response. Both unconditioned and conditioned EMG responses occurred infrequently and were unaffected by any lesion. Unconditioned HR responses and somatomotor threshold determinations to unsignaled electric shock were also unaffected by the lesions. Complete septal lesions increased locomotor activity relative to sham or other septal lesions. Little hippocampal RSA was detected in Ss with medial lesions, but the HR CR was unimpaired in these Ss. Data implicate the septo-hippocampal circuit in classical conditioning of cardiovascular changes and further suggest that diencephalic forebrain structures may modulate forebrain processing of sensory stimulation, perhaps in terms of assessing its biological significance. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Discriminated lateralized eyeblink conditioning in the rabbit: An experimental context for separating specific and general associative influences.

Four experiments demonstrated discriminated lateralized eyeblink conditioning in 38 male rabbits and showed how the phenomenon may be used to differentiate between the reflexive and emotive consequences of Pavlovian conditioning. Exps 1, 2, and 3 characterized how 2 conditioned stimuli (CSs), contemporaneously trained with left vs right paraorbital unconditioned stimuli (UCSs), can produce different CRs, each involving predominant closure of the eye ipsilateral to its UCS. Exp 4 showed how the associative tendencies controlled by additional stimuli could be evaluated by presentations in compound with such discriminanda: A 30-sec stimulus, presumed to acquire a conditioned emotional response but no eyeblink CR, equally potentiated the eyelid CRs elicited by both CSs. A 1,050-msec CS that evoked an eyeblink CR in isolation also increased the responding to both CSs but biased it toward its own lateralized CR. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bilateral cerebellar lesions disrupt conditioned eyelid responses in unrestrained rats.

Electromyographic eyelid responses in unrestrained rats were classically conditioned in a Pavlovian delay paradigm by using a tone conditioned stimulus (CS) and periorbital shock unconditioned stimulus (US). After eyelid conditioning was complete, bilateral electrolytic lesions were made in the dentate-interpositus region of the cerebellar nuclei. Initial eyelid conditioning was reliable and very similar to that previously observed in the rabbit, although the asymptotic eyelid responses contained a short-latency startle response in addition to the usual conditioned and unconditioned responses (CR and UR). Substantial decrements in CRs were observed in 13 of the 14 rats with accurately placed lesions. In contrast, startle responses and URs were unaffected. Results replicate the effects of cerebellar lesions on eyelid CRs in the rabbit and suggest that the anatomical basis of eyelid conditioning in both species is similar. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioning the unconditioned response: Modification of the rabbit's (Oryctolagus cuniculus) unconditioned nictitating membrane response.

Conditioning-specific reflex modification (CRM) occurs when classical conditioning modifies responding to a unconditioned stimulus/stimuli (UCS) in the absence of a conditioned stimulus (CS). Three experiments monitored rabbit (Oryctolagus cuniculus) nictitating membrane unconditioned responses to 5 intensities and 4 durations of periorbital electrical stimulation before and after CS or UCS manipulation. CRM occurred after 12 days of CS-UCS pairings but not following unpaired CS/UCS presentations or restraint. CRM survived CS-alone and CS/UCS-unpaired extinction of the conditioned response (CR) but not presentations of the UCS alone, although CRs remained intact. Thus, CRs could be weakened without eliminating CRM and CRM could be weakened without eliminating CRs. Data indicate CRM is a reliable, associative effect that is more than a generalized CR and may not be explained by habituation, stimulus generalization, contextual conditioning, or bidirectional conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mediodorsal thalamic lesions and Pavlovian conditioning of heart rate and eyeblink responses in the rabbit.

Rabbits received ibotenic acid lesions of the mediodorsal nucleus of the thalamus (MD) or sham lesions. These animals were compared on 4 sessions of Pavlovian eyeblink and heart rate conditioning, in which a tone was the conditioned stimulus/stimuli (CS) and a paraorbital electrical shock was the unconditioned stimulus/stimuli (UCS). Lesions of MD retarded acquisition of the eyeblink conditioned response (CR) and abolished the late-occurring tachycardiac component of the heart rate CR. The data are compatible with previous experiments (H. Groenewegen, 1988), suggesting that MD participated in the sympathetic control associated with somatomotor learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Learning of physiological responses: II. Classical conditioning of the baroreflex.

The baroreflex can be classically conditioned. In neuromuscular blocked (NMB) rats, electrical stimulation of the aortic depressor nerve (ADN) and dopamine-produced blood pressure rise were effective unconditioned stimuli (UCS) for auditory discriminative classical conditioning. The conditioned response (CR) pattern (bradycardia, vasodilatation, and hypotension > 10 torr) closely resembled that of the unconditioned baroreflex. Conditioned stimulus (CS) specificity was demonstrated by discrimination of baroreflex-associated and nonassociated auditory stimuli, and also by elaborating depressor and pressor CRs to auditory CSs, which respectively had been associated with either baro-afferent (depressor) or tail-shock (pressor) UCSs. The conditioned baroreflex-magnitude increased with trials. These findings support quantitative models in which CRs interact with and calibrate the gain and dynamic properties of natural reflexes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Posttraining lesions of the medial prefrontal cortex impair performance of Pavlovian eyeblink conditioning but have no effect on concomitant heart rate changes in rabbits (Oryctolagus cuniculus).

The medial prefrontal cortex (mPFC) plays a critical role in conditioned autonomic adjustments but is not involved in classically conditioned somatomotor responses unless the training conditions include reversal or trace conditioning. The studies showing these effects have all used pretraining lesions. The present study assessed the effects of posttraining lesions on eyeblink (EB) and heart rate (HR) conditioned responses (CRs) in both delay and trace conditioning paradigms in the rabbit (Oryctolagus cuniculus). Posttraining lesions lowered the percentage of EB CRs during retesting compared with pretesting levels for both delay and trace conditioning. Control lesions and pretraining lesions produced no significant effects during retesting. Posttraining lesions had no effect on the HR CR. These findings suggest that a critical mechanism in the mPFC is involved in retrieval of information during EB conditioning but that the mPFC integration of autonomic and somatomotor processes is not critical to this retrieval process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquisition of classically conditioned-related activity in the hippocampus is affected by lesions of the cerebellar interpositus nucleus.

Rabbits were first given left cerebellar interpositus nucleus lesions followed by classical nictitating membrane (NM) conditioning using paired presentations of a tone conditioned stimulus (CS) and an air puff unconditioned stimulus (UCS). Multiple-unit hippocampal activity was monitored over the course of training. In rabbits with anterior interpositus lesions, the acquisition of learned responses and significant increases in training-related hippocampal activity were prevented when paired training was given to the left NM but not when training was switched to the right NM. Rabbits with lesions anterior to the interpositus or in surrounding cerebellar regions failed to show deficits in behavioral responding or hippocampal activity. These results indicate that acquisition of conditioning-related activity in the hippocampus depends on an intact interpositus nucleus of the cerebellum. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modulation of the acquisition of the rabbit eyeblink conditioned response by conditioned contextual stimuli.

Three experiments were conducted to ask if conditioned emotional responses (CERs) controlled by contextual cues modulate the acquisition of eyelid conditioned responses (CRs) to discrete conditioned stimuli (CSs). Experiment 1 showed that 30-s auditory stimuli that were paired with aversive shocks to one paraorbital region or the other controlled discriminated CERs, as measured by potentiation of a startle response. In Experiments 2 and 3, similarly trained 30-s stimuli served as contexts in which 1,050-ms CSs were paired with a paraorbital unconditioned stimulus (US). Reinforced contexts both impaired (Experiments 2A and 2B) and facilitated (Experiment 3B) acquisition of the eyeblink CR, depending on the locus of the USs involved. The data are consistent with the interpretation that CERs controlled by contextual cues facilitate CR acquisition, but do so in the face of blocking effects of CR tendencies also conditioned to the contextual cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Excitatory conditioning of individual Drosophila melanogaster..

Demonstrated, in 5 studies, conditioning of the proboscis extension reflex in D. melanogaster. The presentation of paired (conditioning) stimuli produced (a) an increase in the average number of conditioned responses (CRs) over trials, (b) measured differences in performance levels among individual Ss, and (c) greater conditioning among males than females. The presentation of unpaired (control) stimuli produced significantly lower average levels of acquisition responding and a change in the distribution of individual response patterns. Neither central excitatory state nor sensitization induced by the conditioned stimulus/stimuli (CS) or the unconditioned stimulus/stimuli (UCS) directly affected the CR, whereas UCS preexposure adversely affected performance levels. Presenting the unpaired (extinction) stimuli after conditioning produced less of a decline in responding than did an extinction procedure with removal of the UCS. With the ability to identify individual differences in acquisition and extinction patterns, and given the relatively large samples that can be tested simultaneously on the automated stimulation apparatus, it is suggested that it is now possible to make precise behavioral measurements for the behavior-genetic analysis of D. melanogaster with conditioning as the phenotype. (30 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampus and trace conditioning of the rabbit's classically conditioned nictitating membrane response.

In 2 experiments, 36 New Zealand albino rabbits received classical conditioning of the nictitating membrane response in a trace conditioning paradigm. In this paradigm, a 250-msec tone conditioned stimulus (CS) occurred, after which there was a 500-msec period of time in which no stimuli occurred (the trace interval), followed by a 100-msec air-puff unconditioned stimulus (UCS). In Exp I, lesions of the hippocampus or cingulate/retrosplenial cortex (CRC) disrupted acquisition of the long-latency or adaptive conditioned response (CR) relative to unoperated controls and Ss that received neocortical lesions that spared the CRC. When Ss with hippocampal or CRC lesions were switched to a standard delay paradigm in which the CS and UCS were contiguous in time, they acquired in about the same number of trials as naive Ss. In Exp II, multiple-unit activity in area CA1 of the hippocampus was examined during acquisition of the trace CR. Ss had a 500-msec trace interval (Group T-500), received explicitly unpaired presentations of the CS and UCS, or underwent conditioning with a 2-sec trace interval. Group T-500 acquired the CR in about 500 trials. Early in training, there was a substantial increase in neuronal activity in the hippocampus that began during the CS and persisted through the trace interval. Later in conditioning as CRs emerged, the activity shifted to later in the trace interval and formed a model of the amplitude–time course of the behavioral CR. (65 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampectomy disrupts trace eye-blink conditioning in rabbits.

The role of the hippocampus (HPC) in trace eye-blink conditioning was evaluated using a 100-ms tone conditioned stimulus/stimuli (CS), a 300- or 500-ms trace interval, and a 150-ms air puff unconditioned stimulus/stimuli (UCS). Rabbits received complete hippocampectomy (dorsal & ventral), sham lesions or neocortical lesions. Hippocampectomy produced differential effects in relation to the trace interval used. With a 300-ms trace interval, HPC-lesioned Ss showed profound resistance to extinction after acquisition. With a 500-ms trace interval, HPC-lesioned Ss did not learn the task (only 22% conditioned responses [CRs] after 25 sessions, whereas controls showed >80% after 10 sessions), and on the few trials in which a CR occurred, most were "nonadaptive" short-latency CRs (i.e., they started during or just after the CS and always terminated prior to UCS onset). The authors conclude that the HPC encodes a temporal relationship between CS and UCS, and when the trace interval is long enough (e.g., 500 ms), that the HPC is necessary for associative learning of the conditioned eye-blink response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Preparedness and phobia: Effects of stimulus content on human visceral conditioning.

Conducted 6 experiments to test M. Seligman's (see PA, Vols 45:1675 and 48:1326) preparedness theory of phobia in human classical conditioning of skin conductance and heart rate responses with approximately 12 undergraduates. Conditioned stimuli (CSs) were photographs of plants, human artifacts, and phobia-relevant animals. Both aversive tactile and auditory unconditioned stimuli (UCSs) were assessed. Combined present results indicate that, consistent with results obtained by A. Ohman and colleagues in research conducted between 1975 and 1985 to test Seligman's theory, electrodermal extinction was slower to phobia-relevant stimuli than to other stimuli (and in the present study, was shown to depend on a tactile UCS); however, unlike the findings of Ohman and colleagues, when Ss were told that shocks would be discontinued, phobic CSs extinguished as readily as unprepared CSs. New evidence was obtained for a preparedness effect during acquisition trials: Only Ss receiving phobia-relevant stimuli developed an acceleratory cardiac conditioned response (CR). This acquisition effect was more reliable across experiments than the electrodermal extinction findings and showed less influence of CS—UCS "belongingness." Findings suggest that the preparedness effect is complexly determined and provide evidence that phobic stimuli occasion a unique pattern of conditioned visceral response. (48 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Real-time processing of serial stimuli in classical conditioning of the rabbit's nictitating membrane response.

Real-time models contend that a CS gives rise to a cascade of hypothetical stimuli that govern CRs on a moment-to-moment basis. Experiments with the rabbit nictitating membrane response successfully extended these models to external stimuli. CRs were trained in sequence with an unconditioned stimulus/stimuli (UCS) (CSA–CSB–UCS). When the CSA–CSB interval was shortened, the CR was compressed; when the CSA–CSB interval was lengthened, the CR was broadened. Peaks appeared at 2 places, namely, one following CSA by a period equal to the CS–UCS interval and another following CSB by its CS–UCS interval. Outside the sequence, the individual CSs evoked CRs located between their respective CS–UCS intervals. When, however, the 2 CSs were trained separately, the CRs were appropriate to their respective CS–UCS intervals when tested alone or in sequence. The results are discussed in terms of the J. E. Desmond and J. W. Moore (1988) and S. Grossberg and N. A. Schmajuk (1989) models. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The dopaminergic modulation of fear: Quinpirole impairs the recall of emotional memories in rats.

Past studies examining the contributions of dopamine to fear have produced inconsistent results. The present experiments reevaluated this issue. It was found that systemic pretreatment with the D2 agonist quinpirole before pairing 2 conditioned stimuli (CSs; CS2–CS1) dose dependently blocked the acquisition of second-order fear conditioning. Quinpirole's actions were not due to nonspecific impairments in the ability to perceive the CSs, or form and store an association, because the identical drug pretreatment before pairing the same 2 CSs had no effect on the acquisition of sensory preconditioning. In a separate study, rats were given fear conditioning while untreated and then received extinction sessions while under the influence of quinpirole or its vehicle. Quinpirole pretreatment blocked extinction. Findings suggest that quinpirole decreased fear by blocking the retrieval of a learned association between a CS and unconditioned stimulus (UCS), rather than by devaluing the UCS, which would have resulted from summation of quinpirole's appetitive properties with the aversive properties of fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)