Examination of bilateral eyeblink conditioning in rats.

This experiment monitored eyelid responses bilaterally during delay eyeblink conditioning in rats. Rats were given paired or unpaired training with a tone or light conditioned stimulus (CS) and a unilateral periorbital shock unconditioned stimulus (US). Rats given paired training acquired high levels of conditioned responses (CRs), which occurred in both eyelids. However, acquisition was faster, and the overall percentage of CRs was greater in the eyelid that was ipsilateral to the US. CRs in the eyelid ipsilateral to the US also had shorter onset latencies and larger amplitudes than CRs in the contralateral eyelid. Both eyelids consistently showed high percentages of unconditioned responses (UR) to the US, and the UR amplitude decreased across training sessions in the paired group. The present study demonstrated that CRs occur robustly in both eyelids of rats given eyeblink conditioning, which is similar to previous findings in humans and monkeys. The results also showed that conditioning occurs more prominently in the eyelid that is ipsilateral to the US, which is similar to previous findings in humans, monkeys, dogs, and rabbits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Classical conditioning with electrical stimulation of cerebellum as both conditioned and unconditioned stimulus.

Stimulating electrodes were implanted in rabbit cerebellum, providing an electrical conditioned stimulus (CS) activating cortical parallel fibers and thence Purkinje and other cells, and an electrical unconditioned stimulus (US) activating underlying white matter and eliciting unconditioned responses. Paired CS-US presentations led to the development of conditioned responses, which showed extinction following CS-alone trials and reacquisition with significant savings on reinstatement of paired trials. Increased local excitability as a result of paired training (but not following unpaired stimulus presentations) was observed in cerebellar cortex, as manifested in substantial decreases in CS threshold for response elicitation in all subjects. This preparation offers a model for the study of plastic neuronal interactions within cerebellar networks critically involved in associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Classical conditioning increases membrane-bound protein kinase C in rabbit cerebellum

We examined membrane-bound protein kinase C (PKC) in the cerebellum of rabbits given paired presentations of a tone conditioned stimulus (CS) that co-terminated with a periocular electrical stimulation unconditioned stimulus (US) or unpaired presentations of the CS and US or restraint in the experimental context. PKC activation was measured by quantitative film autoradiography of [3H]phorbol 12,13-dibutyrate ([3H]PBt2) binding in the molecular and granule cells layers of lobule HVI, anterior vermis and Crus I, and in the dentate/interpositus nuclei. There was a statistically significant increase in [3H]PBt2 binding within the molecular layer of lobule HVI in rabbits given paired training relative to controls. The results indicate PKC activation in lobule HVI may be important in acquisition of conditioned eyeblink responses.     

Cerebellar stimulation as an unconditioned stimulus in classical conditioning.

Implanted rabbits with chronic stimulating electrodes in white matter underlying lobule HVI of the cerebellar cortex. Stimulation elicited movements of the face or neck and, when paired with a tone CS, produced learning comparable to that seen with peripheral unconditioned stimulus/stimuli (UCS). CS-alone trials produced extinction. Reinstatement of paired trials produced reacquisition with savings. Additional groups received either explicitly or randomly unpaired CS–UCS trials before paired conditioning. Low-frequency responding during these sessions indicated that the paired training results were associative and not due to pseudoconditioning or sensitization. Explicitly unpaired sessions retarded learning on subsequent paired trials compared with groups that received either randomly unpaired or no CS–UCS preexposure. These results are interpreted in terms of the role of the cerebellum and associated pathways in classical conditioning of motor responses. (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)     

Cerebellar inactivation impairs cross modal savings of eyeblink conditioning.

Eyeblink conditioning using a conditioned stimulus (CS) from one sensory modality (e.g., an auditory CS) is greatly enhanced when the subject is previously trained with a CS from a different sensory modality (e.g., a visual CS). The enhanced acquisition to the second modality CS results from cross modal savings. The current study was designed to examine the role of the cerebellum in establishing cross modal savings in eyeblink conditioning with rats. In the first experiment rats were given paired or unpaired presentations with a CS (tone or light) and an unconditioned stimulus. All rats were then given paired training with a different modality CS. Only rats given paired training showed cross modal savings to the second modality CS. Experiment 2 showed that cerebellar inactivation during initial acquisition to the first modality CS completely prevented savings when training was switched to the second modality CS. Experiment 3 showed that cerebellar inactivation during initial cross modal training also prevented savings to the second modality stimulus. These results indicate that the cerebellum plays an essential role in establishing cross modal savings of eyeblink conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Classical conditioning of the rabbit eyelid response with a mossy-fiber stimulation CS: II. Lateral reticular nucleus stimulation.

Stimulation of mossy fibers arising from the pontine nuclei can be used as a conditioned stimulus (CS) during classical conditioning of the eyelid/nictitating membrane response (NM). In the present experiment we stimulated another source of mossy fibers, the lateral reticular nucleus (LRN), as a CS for NM conditioning. LRN stimulation was an effective CS, resulting in learning, and the conditioned response to LRN stimulation showed normal extinction. Unpaired presentation of CS and US did not result in pseudo-conditioning. Lesions of the cerebellar dentate-interpositus region abolished the conditioned response but left the unconditioned reflex response intact. We suggest that mossy fibers may normally carry CS information to the cerebellum. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Evidence of plasticity in the pontocerebellar conditioned stimulus pathway during classical conditioning of the eyeblink response in the rabbit

Electrical stimulation thresholds required to elicit eyeblinks with either pontine or cerebellar interpositus stimulation were measured before and after classical eyeblink conditioning with paired pontine stimulation (conditioned stimulus, CS) and corneal airpuff (unconditioned stimulus, US). Pontine stimulation thresholds dropped dramatically after training and returned to baseline levels following extinction, whereas interpositus thresholds and input-output functions remained stable across training sessions. Learning rate, magnitude of threshold change, and electrode placements were correlated. Pontine projection patterns to the cerebellum were confirmed with retrograde labeling techniques. These results add to the body of literature suggesting that the pons relays CS information to the cerebellum and provide further evidence of synaptic plasticity in the cerebellar network.     

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)     

Effect of tone-dependent fear conditioning on heart rate and behavior of C57BL/6N mice.

The effects of the temporal sequence of tone (conditioned stimulus [CS]) and footshock (unconditioned stimulus [US]) during training (acquisition) on tone-dependent retention were studied in mice. Freezing increased significantly as an associative behavioral response in mice subjected to CS paired with US or after unpaired by 30 s in the memory test performed 24 hr after training. In the home cage of freely moving mice implanted with an electrocardiogram transmitter, CS triggered a strong tachycardiac response in the memory test. Heart rate (HR) increased from about 580 bpm to more than 750 bpm, and HR variability decreased significantly. The inhibition of the HR increase by the nonspecific β-adrenergic antagonist sotalol indicated the strong sympathetic contribution to the tachycardiac response. CS evoked a significant but minor HR increase in mice subjected to either CS or US only or CS and US unpaired by 60 s. Thus, HR and HR variability reflected associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fear conditioning in panic disorder: Enhanced resistance to extinction.

Enhanced conditionability has been proposed as a crucial factor in the etiology and maintenance of panic disorder (PD). To test this assumption, the authors of the current study examined the acquisition and extinction of conditioned responses to aversive stimuli in PD. Thirty-nine PD patients and 33 healthy control participants took part in a differential aversive conditioning experiment. A highly annoying but not painful electrical stimulus served as the unconditioned stimulus (US), and two neutral pictures were used as either the paired conditioned stimulus (CS+) or the unpaired conditioned stimulus (CS-). Results indicate that PD patients do not show larger conditioned responses during acquisition than control participants. However, in contrast to control participants, PD patients exhibited larger skin conductance responses to CS+ stimuli during extinction and maintained a more negative evaluation of them, as indicated by valence ratings obtained several times throughout the experiment. This suggests that PD patients show enhanced conditionability with respect to extinction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired classical eyeblink conditioning in cerebellar-lesioned and Purkinje cell degeneration (pcd) mutant mice

Converging lines of evidence from rabbits, rats, and humans argue for the crucial involvement of the cerebellum in classical conditioning of the eyeblink/nictitating membrane response in mammals. For example, selective lesions (permanent or reversible) of the cerebellum block both acquisition and retention of eyeblink conditioning. Correspondingly, electrophysiological and brain-imaging studies indicate learning-related plasticity in the cerebellum. The involvement of the cerebellum in eyeblink conditioning is also supported by stimulation studies showing that direct stimulation of the two major afferents to the cerebellum (the mossy fibers emanating from the pontine nucleus and climbing fibers originating from the inferior olive) can substitute for the peripheral conditioned stimulus (CS) and unconditioned stimulus (US), respectively, to yield normal behavioral learning. In the present study, we examined the relative contribution of the cerebellar cortex versus deep nuclei (specifically the interpositus nucleus) in eyeblink learning by using mutant mice deficient of Purkinje cells, the exclusive output neurons of the cerebellar cortex. We report that Purkinje cell degeneration (pcd) mice exhibit a profound impairment in the acquisition of delay eyeblink conditioning in comparison with their wild-type littermates. Nevertheless, the pcd animals did acquire a subnormal level of conditioned eyeblink responses. In contrast, wild-type mice with lesions of the interpositus nucleus were completely unable to learn the conditioned eyeblink response. These results suggest that both cerebellar cortex and deep nuclei are important for normal eyeblink conditioning.     

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)     

Amygdala lesions block conditioned enhancement of the early component of the rat eyeblink reflex.

A tone-conditioned stimulus (CS) previously paired with a grid shock unconditioned stimulus (US) can greatly enhance the early electromyographic (EMG) component (RI) of the rat eyeblink reflex. The hypothesis that the central nucleus of the amygdala (ACe) is an essential part of the circuitry mediating conditioned RI enhancement was tested. After bilateral ACe lesions (L) or a sham operation (S), rats received paired presentations of the CS and US (P) or explicitly unpaired CS and US presentations (U), resulting in 4 groups: P/S, P/L, U/S, and U/L. ACe lesions completely prevented conditioned RI enhancement, which was only exhibited in Group P/S. In the latter group, the "preextinction" conditioned enhancement effect was roughly a 2-fold increase in the RI magnitude. Circuit-level mechanisms are discussed, and some advantages of the eyeblink EMG response in this general conditioning paradigm are considered. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mechanism of the radiation-protective effect of indralin

Output from the interpositus nucleus can inhibit the inferior olive, probably via the GABA-ergic nucleo-olivary pathway. It has been suggested that the function of this inhibition might be to regulate synaptic plasticity resulting from parallel fibre/climbing fibre interaction in cerebellar Purkinje cells, by providing negative feedback information to the olive. Thus, when a learned response, generated by the interpositus nucleus, reaches a sufficient amplitude, the olive would be inhibited and further learning blocked. This suggestion was tested in a classical conditioning paradigm. Decerebrate ferrets were trained using electrical skin stimulation of the forelimb as the conditioned stimulus (CS) and periorbital stimulation as the unconditioned stimulus (US). Climbing fibre responses evoked in Purkinje cells by the US were recorded as surface field potentials in the part of the c3 zone controlling eyeblink. It was found that the CS did not inhibit the olive at the beginning of training, but when conditioned responses were large, the olive was inhibited by the CS in some animals. After a number of unpaired CS presentations, which caused extinction of the conditioned response, the inhibition disappeared. The size of individual conditioned responses correlated negatively with the size of the climbing fibre responses evoked by the US. Climbing fibre responses evoked by direct stimulation of the olive were also inhibited. It was concluded that cerebellar output during performance of a conditioned response inhibits the inferior olive. The results thus support the hypothesis of a cerebellar locus of conditioning and are consistent with the proposed role of cerebello-olivary inhibition.     

Conditioning-specific modification of the rabbit's unconditioned nictitating membrane response.

Robust classical conditioning modifies responding to the unconditioned stimulus (US) in the absence of the conditioned stimulus (CS), a phenomenon the researchers called conditioning-specific reflex modification. Unconditioned responses (URs) to periorbital stimulation varying in intensity and duration were assessed before and after 1, 3, or 6 days of paired, explicitly unpaired, or no presentations of tone and electrical stimulation. After 3 days of pairings, conditioned responding (CRs) reached 94%, and there was an increase in latency to the peak of URs. The peak latency increase was replicated in a 2nd experiment where rabbits reached asymptotic conditioning during 6 days of pairings. There was also a conditioning-specific increase in the amplitude of URs. There were no UR changes as a function of low level of CRs following 1 day of pairings. Data suggest that there are learning-specific changes in pathways mediating the US/UR, as well as in those mediating the CS/CR. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Potentiation of the acoustic startle response by a conditioned stimulus paired with acoustic startle stimulus in rats.

The hypothesis that the standard acoustic startle habituation paradigm contains the elements of Pavlovian fear conditioning was tested. In a potentiated startle response paradigm, a startle stimulus and a light conditioned stimulus (CS) were paired. A startle stimulus then was tested alone or following the CS. Freezing behavior was measured to index conditioned fear. The startle response was potentiated on CS trials, and rats froze more in CS than in non-CS periods. In Experiment 1, response to a previously habituated, weak startle stimulus was potentiated. In Experiment 2, response to the same stimulus used as the unconditioned stimulus (US) in training was potentiated. This CS-potentiated response retarded the course of response decrements over training sessions as compared with an explicitly unpaired control group. Conditioned fear is a standard feature of this habituation paradigm, serves to potentiate the startle response, and provides an associative dimension lacking in the habituation process per se. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned-reflex facilitation in young and older adults

Young (18-30 years) and elderly (63-88 years) human subjects received 70 trials of single-cue classical eyeblink conditioning (paired group), or 70 explicitly unpaired presentations of the tone conditioned stimulus (CS) and airpuff unconditioned stimulus (unpaired group). Before and after conditioning, reflex-eliciting white noise and corneal airpuff stimuli were presented alone or paired with the CS to investigate the effects of conditioning on eyeblink reflex amplitude. The results showed increased conditioned responses in the paired group compared to the unpaired group for the young but not the elderly subjects. There was, however, evidence of conditioned facilitation of noise-elicited reflexes in both young and elderly subjects. These data indicate that conditioned facilitation of the startle reflex may be a sensitive indicator of classical conditioning processes in human subjects.     

The effects of backward pairings on the conditioning of the albino rabbit's jaw movement and nictitating membrane responses.

Evaluated backward conditioning of appetitive jaw movement and aversive nictitating membrane responses in rabbits, using 3 procedures: test trials, forward acquisition of the same response, and crossmotivational acquisition of the other response system. In both experiments, backward conditioning consisted of 3 conditioned stimulus/stimuli (CS) alone and 22 CS and unconditioned stimulus/stimuli (UCS) pairings. Contrasting the backward conditioning group with explicitly unpaired and no-treatment controls revealed that backward pairings produced no associative effects. The forward acquisition and crossmotivational acquisition tests suggest that excitatory backward acquisition of jaw movement was obtained. The forward acquisition test identified weak inhibitory conditioning of nictitating membrane responses, but the crossmotivational test implicated excitatory conditioning. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

An auditory conditioned stimulus modulates unconditioned stimulus-elicited neuronal activity in the cerebellar anterior interpositus and dentate nuclei during nictitating membrane response conditioning in rabbits.

Investigated the effects of the presentation of an auditory conditioned stimulus (CS) on unconditioned stimulus (UCS)-elicited neuronal activity in the anterior interpositus (AIPN) and dentate (DN) nuclei of the cerebellum during the initial stages of classical conditioning of the nictitating membrane (NM) response in rabbits. In Exp 1, a 500-msec CS (but not a 30-msec CS) facilitated UCS-elicited single-unit activity in the AIPN and depressed UCS-elicited activity in the DN during training. In Exp 2, lesions of the AIPN but not of the DN prevented acquisition of conditioned NM responses. The results are interpreted within the framework of a model of classical conditioning that proposes that conditioned neuronal activity that underlies behavioral plasticity develops from the modulation of UCS-elicited neuronal activity by the CS. (PsycINFO Database Record (c) 2010 APA, all rights reserved)