Inactivation of sodium channel Scn8A (Nav1.6) in purkinje neurons impairs learning in Morris Water Maze and delay but not trace eyeblink classical conditioning.

To examine the isolated effects of altered currents in cerebellar Purkinje neurons, the authors used Scn8aflox/flox, Purkinje cell protein-CRE (Pcp-CRE) mice in which Exon 1 of Scn8a is deleted only in Purkinje neurons. Twenty male Purkinje Scn8a knockout (PKJ Scn8a KO) mice and 20 male littermates were tested on the Morris water maze (MWM). Subsequently, half were tested in 500-ms delay and half were tested in 500-ms trace eyeblink conditioning. PKJ Scn8a KO mice were impaired in delay conditioning and MWM but not in trace conditioning. These results provide additional support for the necessary participation of cerebellar cortex in normal acquisition of delay eyeblink conditioning and MWM and raise questions about the role, if any, of cerebellar cortex in trace eyeblink conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delay discrimination and reversal eyeblink classical conditioning in abstinent chronic alcoholics.

[Correction Notice: An erratum for this article was reported in Vol 23(2) of Neuropsychology (see record 2009-02621-003). The lifetime drinking data listed in Table 1 on p. 198 was not correctly calculated and underestimated lifetime exposure to alcohol. The corrected lifetime variables from that table are included.] Evidence has shown that alcoholism leads to volume reductions in brain regions critical for associative learning using the eyeblink classical conditioning paradigm (EBCC). Evidence indicates that cerebellar shrinkage causes impairment in simple forms of EBCC, whereas changes in forebrain structures result in impairment in more complex tasks. In this study, the ability of abstinent alcoholics and matched control participants to acquire learned responses during delay discrimination and discrimination reversal was examined and related to severity of drinking history and neuropsychological performance. During discrimination learning, one tone (CS+) predicted the occurrence of an airpuff (unconditioned stimulus), and another tone (CS-) served as a neutral stimulus; then the significance of the tones was reversed. Alcoholics who learned the initial discrimination were impaired in acquiring the new CS+ after the tones reversed; this is a function that has previously been linked to forebrain structures. It is suggested that a factor important to alcoholic addiction may be the presence of alcoholic-related associative responses that interfere with the ability to learn new more adaptive associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Procedural memory system supports single cue trace eyeblink conditioning in medial temporal lobe amnesia.

A number of studies investigating trace eyeblink conditioning have found impaired, but not eliminated, acquisition of conditioned responses (CRs) in both animals and humans with hippocampal removal or damage. The underlying mechanism of this residual learning is unclear. The present study investigated whether the impaired level of learning is the product of residual hippocampal function or whether it is mediated by another memory system that has been shown to function normally in delay eyeblink conditioning. Performance of bilateral medial temporal lobe amnesic patients who had a prior history of participating in eyeblink conditioning studies was compared to a control group with a similar training history and to an untrained control group in a series of single cue trace conditioning tasks with 500 ms, 250 ms, and 0 ms trace intervals. Overall, patients acquired CRs to a level similar to the untrained controls, but were significantly impaired compared to the trained controls. The pattern of acquisition suggests that amnesic patients may be relying on the expression of previously acquired, likely cerebellar based, procedural memory representations in trace conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Standard delay eyeblink classical conditioning is independent of awareness.

P. F. Lovibond and D. R. Shanks (see record 2002-00340-001) suggested that all forms of classical conditioning depend on awareness of the stimulus contingencies. This article considers the available data for eyeblink classical conditioning, including data from 2 studies (R. E. Clark, J. R. Manns, & L. R. Squire, 2001; J. R. Manns, R. E. Clark, & L. R. Squire, 2001) that were completed too recently to have been considered in their review. In addition, in response to questions raised by P. F. Lovibond and D. R. Shanks, 2 new analyses of data are presented from studies published previously. The available data from humans and experimental animals provide strong evidence that delay eyeblink classical conditioning (but not trace eyeblink classical conditioning) can be acquired and retained independently of the forebrain and independently of awareness. This conclusion applies to standard conditioning paradigms; for example, to single-cue delay conditioning when a tone is used as the conditioned stimulus (CS) and to differential delay conditioning when the positive and negative conditioned stimuli (CS+ and CS-) are a tone and white noise. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reflex facilitation during eyeblink conditioning and subsequent interpositus nucleus inactivation in the rabbit (Orycotolagus cuniculus).

In eyeblink conditioning in the rabbit (Oryctolagus cuniculus), not only is a conditioned response (CR) acquired, but also the original reflex is modified as a function of training. In Experiment 1, by comparing unconditioned responses in unpaired and paired groups, 3 types of reflex facilitation were distinguished. One type was linked to exposure to the unconditioned stimuli (USs) and/or experimental setting. The 2nd type was related to the formation of the memory trace for conditioned eyeblink. The 3rd type was linked to the conditioned stimulus immediately preceding the US in the paired group. In Experiment 2, reversible inactivation of the interpositus nucleus (IPN) abolished the CR and reduced the CR-related reflex facilitation, indicating that the latter depends on the plasticity of the IPN. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial auditory thalamic nuclei are necessary for eyeblink conditioning.

The auditory conditioned stimulus (CS) pathway that is necessary for delay eyeblink conditioning was investigated with induced lesions of the medial auditory thalamus contralateral to the trained eye in rats. Rats were given unilateral lesions of the medial auditory thalamus or a control surgery followed by twenty 100-trial sessions of delay eyeblink conditioning with a tone CS and then five sessions of delay conditioning with a light CS. Rats that had complete lesions of the contralateral medial auditory thalamic nuclei, including the medial division of the medial geniculate, suprageniculate, and posterior intralaminar nucleus, showed a severe deficit in conditioning with the tone CS. Rats with complete lesions also showed no cross-modal facilitation (savings) when switched to the light CS. The medial auditory thalamic nuclei may modulate activity in a short-latency auditory CS pathway or serve as part of a longer latency auditory CS pathway that is necessary for eyeblink conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Eyeblink classical conditioning in the preweanling lamb.

Classical conditioning of eyeblink responses has been one of the most important models for studying the neurobiology of learning, with many comparative, ontogenetic, and clinical applications. The current study reports the development of procedures to conduct eyeblink conditioning in preweanling lambs and demonstrates successful conditioning using these procedures. These methods will permit application of eyeblink conditioning procedures in the analysis of functional correlates of cerebellar damage in a sheep model of fetal alcohol spectrum disorders, which has significant advantages over more common laboratory rodent models. Because sheep have been widely used for studies of pathogenesis and mechanisms of injury with many different prenatal or perinatal physiological insults, eyeblink conditioning can provide a well-studied method to assess postnatal behavioral outcomes, which heretofore have not typically been pursued with ovine models of developmental insults. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Extracellular amino acid levels in the interpositus nucleus during classical eyeblink conditioning in alert cats.

The extracellular levels of selected amino acids in the cerebellar posterior interpositus nucleus (PIN) during classical eyeblink conditioning was analyzed in alert cats using a delay paradigm. Animals were prepared for the chronic recording of eyelid movements (with the magnetic search-coil technique) and the electromyographic activity of the orbicularis oculi muscle. With the help of a guide and push-pull cannulae, selected PIN sites were perfused daily during classical eyeblink conditioning. The perfusate was sampled at intervals of 5 min and analyzed with a high-pressure liquid chromatography- electrochemical detection (HPLC-EC) method. The analysis of push-pull perfusate revealed a significant increase in the release of glycine, taurine, and glutamate across the successive conditioning sessions, in parallel with the acquisition of eyelid conditioned responses (CRs). Both CRs and extracellular levels of these three amino acids returned to control values during extinction. Other amino acids (alanine, GABA, glutamine, serine, and threonine) did not undergo modifications in their extracellular concentrations across the training. Results are discussed with regard to the role of PIN in this type of associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of the cerebellar interpositus nucleus in short and long term memory for trace eyeblink conditioning.

In previous studies the cerebellar interpositus (IP) nucleus, but not the hippocampus, was shown to be necessary both for initial learning and retention and for long-term retention of the standard delay eyeblink conditioned response (CR). However, in the trace eyeblink CR procedure, the hippocampus is also necessary for initial learning and retention, but not for long-term retention. Here the authors evaluate the role of the IP nucleus in both initial learning and retention, and in long-term retention of the trace eyeblink CR, using muscimol infusion to reversibly inactivate the IP nucleus. For the short-term study, there were two subgroups, the first sequentially passed through acquisition, inactivation, and reacquisition phases, whereas the second subgroup went through inactivation, acquisition, and inactivation phases. For the long-term study, the rabbits acquired the CR and then rested for a month. Next, they were distributed into two subgroups: with or without retention training, and finally went through inactivation and reacquisition phases. The results showed that the prelearning IP nucleus inactivation prevented the acquisition of the trace CR, whereas the postlearning inactivation reversibly abolished the expression of both the short- and long-term CR. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

UCS intensity and performance in eyelid conditioning.

Studies of the effects of UCS intensity on performance in human eyelid conditioning are reviewed, particularly with respect to a recent claim that this variable determines the proportion of Ss who condition and not the performance level of individual Ss. The evidence reviewed clearly indicates that UCS intensity does affect the level of performance in Ss who condition. The function involved appears to be negatively accelerated and to approach an asymptote within a relatively small range of intensity values. These effects of UCS intensity are interpreted as reflecting both motivational and associative factors. (28 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exploration of cerebellar-dependent associative learning in schizophrenia: Effects of varying and shifting interstimulus interval on eyeblink conditioning.

Eyeblink conditioning abnormalities have been reported in schizophrenia, but the extent to which these anomalies are evident across a range of delay intervals (i.e., interstimulus intervals; ISIs) is unknown. In addition, the effects of ISI shifts on learning are unknown, though such manipulations can be informative about the plasticity of cerebellar timing functions. Therefore, the primary purpose of the present study was to investigate the interactions between ISI manipulations and learning in schizophrenia. A standard delay eyeblink conditioning procedure with four different interstimulus intervals (ISIs; 250, 350, 550, 850 ms) was employed. Each eyeblink conditioning experiment was immediately followed by another with a different ISI, thus permitting the characterization of conditioned response (CR) learning at one ISI and the extent to which CRs could be generated at a different latency following an ISI shift. Collapsing across all conditions, the schizophrenia group (n = 55) had significantly fewer conditioned responses and longer onset latencies than age-matched controls (n = 55). Surprisingly, shifting to a new ISI had negligible effects on conditioned response rates in both groups. These findings contribute to evidence of robust eyeblink conditioning abnormalities in schizophrenia and suggest impaired cerebellar function, but underscore the need for more research to clarify the source of these abnormalities and their relationship to clinical manifestations of schizophrenia. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Decremental effects of context exposure following delay eyeblink conditioning in rabbits.

The conditioning context arises from the relatively static features of the training environment. In rabbit eyeblink conditioning, procedures that retard acquisition (conditioned stimulus [CS] preexposure, unconditioned stimulus preexposure, blocking manipulations) are attenuated by context changes. In this article the authors investigate the effect of context exposure after initial delay conditioning. After conditioned responses (CRs) were established, one group received 6 sessions of context exposure, whereas control groups either remained in their home cages or received exposure to handling and a novel context. Thereafter, all groups received CS-alone testing. The expression of CRs was substantially reduced following context exposure relative to any retention loss in the home-cage control. Exposure to handling and a novel context facilitated the CRs rather than reducing them. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Prefrontal control of trace versus delay eyeblink conditioning: Role of the unconditioned stimulus in rabbits (Oryctolagus cuniculus).

The conditioned eyeblink (EB) response was studied with trace conditioning procedures in rabbits (Oryctolagus cuniculus) with lesions to the medial prefrontal cortex (mPFC) or sham lesions. Three experiments were performed in which either periorbital shock or a corneal airpuff served as the unconditioned stimulus (US) in separate groups of sham or mPFC-lesioned rabbits. Acquisition of the EB conditioned response (CR) was faster and reached a higher asymptote with the eyeshock US than with the airpuff US. However, mPFC lesion-induced trace conditioning deficits were obtained only in the groups that received the airpuff US. All rabbits showed normal delay conditioning and extinction. These results suggest that mPFC mediates trace EB conditioning when emotional arousal is low. However, in circumstances when emotional arousal may be high (i.e., during exposure to aversive periorbital shock), other structures (such as amygdala) may be activated to permit learning even in the absence of input from mPFC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal theta-band activity and trace eyeblink conditioning in rabbits.

The authors examined the relationship between hippocampal theta activity and trace eyeblink conditioning. Hippocampal electrophysiological local field potentials were recorded before, during, and after conditioning or explicitly unpaired training sessions in adult male New Zealand White rabbits. As expected, a high relative power of theta activity (theta ratio) in the hippocampus predicted faster acquisition of the conditioned response during trace conditioning but, contrary to previous results obtained using the delay paradigm, only in the initial stage of learning. The presentation of the conditioned stimulus overall elicited an increase in the hippocampal theta ratio. The theta ratio decreased in the unpaired group as a function of training, remained high throughout conditioning in the fast learners, and rapidly increased in the slow learners initially showing a low theta ratio. Our results indicate a reciprocal connection between the hippocampal oscillatory activity and associative learning. The hippocampal theta ratio seems to reflect changes and differences in the subjects’ alertness and responsiveness to external stimuli, which affect the rate of learning and are, in turn, affected by both conditioning and unpaired training. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Exploring prefrontal cortical memory mechanisms with eyeblink conditioning.

Several studies in nonhuman primates have shown that neurons in the dorsolateral prefrontal cortex have activity that persists throughout the delay period in delayed matching to sample tasks, and age-related changes in the microcolumnar organization of the prefrontal cortex are significantly correlated with age-related declines in cognition. Activity that persists beyond the presentation of a stimulus could mediate working memory processes, and disruption of those processes could account for memory deficits that often accompany the aging process. These potential memory and aging mechanisms are being systematically examined with eyeblink conditioning paradigms in nonprimate mammalian animal models including the rabbit. The trace version of the conditioning paradigm is a particularly good system to explore declarative memory since humans do not acquire trace conditioning if they are unable to become cognitively aware of the association between a conditioning tone and an airpuff to the eye. This conditioning paradigm has been used to show that the hippocampus and cerebellum interact functionally since both conditioned responses and conditioned hippocampal pyramidal neuron activity are abolished following lesions of the cerebellar nuclei and since hippocampal lesions prevent or abolish trace conditioned blinks. However, because there are no direct connections between the hippocampal formation and the cerebellum, and because the hippocampus is not necessary for trace conditioning after a period of consolidation has elapsed, we and others have been examining the prefrontal cortex for its role in forebrain-dependent trace eyeblink conditioning. This review examines some of the literature which suggests that the prefrontal cortex serves to orchestrate a neuronal network that interacts with the cerebellum to mediate adaptively timed conditioned responses. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Eyeblink conditioning leads to fewer synapses in the rabbit cerebellar cortex.

Eyeblink conditioning involves the pairing of a conditioned stimulus (tone) to an aversive unconditioned stimulus (air puff). Although the circuitry that underlies this form of learning is well defined, synaptic changes in these structures have not been fully investigated. This experiment examined synaptic structural plasticity in the cerebellar cortex, a structure that has been found to modulate the acquisition and timing of the conditioned response. Long-term depression of Purkinje cells (PCs) in the cerebellar cortex has been proposed as a mechanism for releasing inhibition of the interpositus nuclei, a structure critical for the formation of the CR. Adult albino rabbits were randomly allocated to either a paired, unpaired, or exposure-only condition. The results showed a significant decrease in the number of excitatory synapses in the outer layer of the cerebellar cortex in the conditioned rabbits compared with controls. This finding suggests that a reduction in the number of excitatory synapses may contribute to the lasting depression of PC activity that is associated with eyeblink conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delay eyeblink classical conditioning is impaired in Fragile X syndrome.

The authors examined 400 ms delay eyeblink classical conditioning in 20 participants with Fragile X syndrome ages 17 to 77 years, and 20 age-matched, healthy control participants. The participants in the Fragile X group demonstrated impaired learning and abnormal conditioned response timing. Adults with Fragile X (n = 16) were also tested at two successive 12-month follow-up sessions to examine reacquisition and long-term retention. Participants in groups who were older and younger than 45 years demonstrated significant learning during each reacquisition session. Younger participants demonstrated greater retention of the conditioned stimulus/unconditioned stimulus association at each follow-up session than older participants. Fragile X impairs the acquisition and timing of conditioned eyeblink responses, but with repeated training adults with Fragile X syndrome show significant plasticity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impaired eyeblink conditioning in 78kDa-glucose regulated protein (GRP78)/immunoglobulin binding protein (BiP) conditional knockout mice.

Evidence grows that the cerebellum and its associated circuitry are the essential neural substrates for standard delay classical eyeblink conditioning. To further investigate the relative roles of the cerebellar cortex and nuclei in eyeblink conditioning, a novel mouse model with Purkinje cell atrophy was studied. The 78kDa-glucose regulated protein, a chaperone molecule, was knocked out leading to postnatal Purkinje cell degeneration (Wang et al., 2010), and standard delay eyeblink conditioning was performed in the conditional knockout mice. Learning was impaired, yet not completely prevented. Histological studies showed a reduction in the cell number and the size of the anterior interpositus nucleus. When the anterior interpositus nucleus was lesioned bilaterally, eyeblink conditioning was completely prevented. The important roles of both cerebellar cortex and AIP nucleus in eyeblink conditioning were seen. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Evaluative conditioning in humans: A meta-analysis.

This article presents a meta-analysis of research on evaluative conditioning (EC), defined as a change in the liking of a stimulus (conditioned stimulus; CS) that results from pairing that stimulus with other positive or negative stimuli (unconditioned stimulus; US). Across a total of 214 studies included in the main sample, the mean EC effect was d = .52, with a 95% confidence interval of .466–.582. As estimated from a random-effects model, about 70% of the variance in effect sizes were attributable to true systematic variation rather than sampling error. Moderator analyses were conducted to partially explain this variation, both as a function of concrete aspects of the procedural implementation and as a function of the abstract aspects of the relation between CS and US. Among a range of other findings, EC effects were stronger for high than for low contingency awareness, for supraliminal than for subliminal US presentation, for postacquisition than for postextinction effects, and for self-report than for implicit measures. These findings are discussed with regard to the procedural boundary conditions of EC and theoretical accounts about the mental processes underlying EC. (PsycINFO Database Record (c) 2010 APA, all rights reserved)