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PubMedDate not supplied

Expression of the immediate-early gene-encoded protein Egr-1 (zif268) during in vitro classical conditioning.

Expression of the immediate-early genes (IEGs) has been shown to be induced by activity-dependent synaptic plasticity or behavioral training and is thought to play an important role in long-term memory. In the present study, we examined the induction and expression of the IEG-encoded protein Egr-1 during an in vitro neural correlate of eyeblink classical conditioning. The results showed that Egr-1 protein expression as determined by immunocytochemistry and Western blot analysis rapidly increased during the early stages of conditioning and remained elevated during the later stages. Further, expression of Egr-1 protein required NMDA receptor activation as it was blocked by bath application of AP-5. These findings suggest that the IEG-encoded proteins such as Egr-1 are activated during relatively simple forms of learning in vertebrates. In this case, Egr-1 may have a functional role in the acquisition phase of conditioning as well as in maintaining expression of conditioned responses.

Animals↗
PubMed1999

Classical conditioning of the human blood pressure response.

The object of this experiment was to demonstrate that blood pressure responses could be classically conditioned in human subjects and to describe the topography of the conditioned response. Despite clear evidence for classical blood pressure conditioning in animals there is little evidence concerning a clear demonstration of the phenomenon in human subjects, and no description of the form of the conditioned response. A 'neutral' 8-s 70-db tone (CS) was paired with a 500-ms electric shock (UCS) in a delay conditioning paradigm. Conditioned subjects were compared to a control group that received the CS and UCS on a truly random schedule. The subjects in the conditioning group showed a conditioned blood pressure response that emerged during the last 4 s of the 8-s CS. The results differ from those obtained from animals, where the CR typically emerges during the first half of the CS. These data may have implications for the role of learning in hypertensive disorders.

Acoustic Stimulation↗
PubMed1997

Mediation of classical conditioning in Aplysia californica by long-term potentiation of sensorimotor synapses.

Long-term potentiation (LTP) is considered an important neuronal mechanism of learning and memory. Currently, however, there is no direct experimental link between LTP of an identified synapse and learning. A cellular analog of classical conditioning in Aplysia was used to determine whether this form of invertebrate learning involves N-methyl-D-aspartate (NMDA)-type LTP. The NMDA receptor-antagonist dl-2-amino-5-phosphonovalerate significantly disrupted synaptic enhancement after associative training but did not disrupt synaptic enhancement after nonassociative training. Thus, classical conditioning in Aplysia appears to be mediated, in part, by LTP due to activation of NMDA-related receptors.

2-Amino-5-phosphonovalerate↗
PubMed2002

Cortical spreading depression and involvement of the motor cortex, auditory cortex, and cerebellum in eyeblink classical conditioning of the rabbit.

The interrelationships of cerebellar and cerebral neural circuits in the eyeblink paradigm were explored with the controlled application of cortical spreading depression (CSD) and lidocaine in the New Zealand albino rabbit. The initial research focus was directed toward the involvement of the motor cortex in the conditioned eyeblink response. However, CSD timing and triangulation results indicate that other areas in the cerebral cortex, particularly the auditory cortex (acoustic conditioned stimulus), appear to be critical for the CSD effect on the eyeblink response. In summary: (1) CSD can be elicited, monitored, and timed and its side effects controlled in 97% of awake rabbits in the right and/or left cerebral hemisphere(s) during eyeblink conditioning. (2) The motor cortex appears to play little or no part in classical conditioning of the eyeblink in the rabbit in the delay paradigm. (3) Inactivating the auditory cortex with CSD or lidocaine temporarily impairs the conditioned response during the first 5 to 15 days of training, but has little effect past that point.

Animals↗
PubMed2004

The effects of ethanol on the developing cerebellum and eyeblink classical conditioning.

In rats, developmental ethanol exposure has been used to model the central nervous system deficits associated with human fetal alcohol syndrome. Binge-like ethanol exposure of neonatal rats depletes cells in the cerebellum, including Purkinje cells, granule cells, and deep nuclear cells, and produces deficits in simple tests of motor coordination. However, the extent to which anatomical damage is related to behavioral deficits has been difficult to estimate. Eyeblink classical conditioning is known to engage a discrete brain stem-cerebellar circuit, making it an ideal test of cerebellar functional integrity after developmental ethanol exposure. Eyeblink conditioning is a simple form of motor learning in which a neutral stimulus (such as a tone) comes to elicit an eyeblink when repeatedly paired with a stimulus that evokes an eyeblink prior to training (such as mild periorbital stimulation). In eyeblink conditioning, one of the deep cerebellar nuclei, the interpositus nucleus, as well as specific Purkinje cell populations, are sites of convergence for tone conditioned stimulus and somatosensory unconditioned stimulus information, and, together with brain stem nuclei, provide the necessary and sufficient substrate for the learned response. A series of studies have shown that eyeblink conditioning is impaired in both weanling and adult rats given binge-like exposure to ethanol as neonates. In addition, interpositus nucleus neurons from ethanol-exposed rats showed impaired activation during eyeblink conditioning. These deficits are accompanied by a permanent reduction In the deep cerebellar nuclear cell population. Because particular cerebellar cell populations are utilized in well-defined ways during eyeblink conditioning, conclusions regarding the underlying neural substrates of behavioral change after developmental ethanol exposure are greatly strengthened.

Animals↗
PubMed1985

Differentiation between classically conditioned and cognitively based neurotic fears: two pilot studies.

The ability of clinical trainees to learn to distinguish between classically conditioned and cognitively based neurotic fears was examined in two small-scale studies. The first study showed that they readily learned to make the distinction on the basis of transcripts of key excerpts of actual patient sessions, and that ability to do so increased with training. The second study showed a high degree of inter-rater reliability among assessor ratings of fear type on the basis of independent interviews of phobic patients.

Clinical Competence↗
PubMed1989

Classical conditioning of meaning--II. A replication and triplet associative extension.

The meaning associated with verbal stimuli is modifiable by classical conditioning, suggesting that such "language conditioning" may be used clinically to modify a client's maladaptive associative history. The current research investigated the existence and generalizability of this phenomenon by attempting to replicate Staats and Staats' (1957) language conditioning effect and then extend it to a triplet conditioning paradigm (CS2----CS1----UCS). Previous research by the current authors replicated language conditioning, yet failed to extend it to a higher-order situation. Significant conditioning was obtained to the CS1, particularly for aware subjects, but no conditioning occurred to the CS2. Implications for verbal conditioning theory and clinical practice are discussed.

Adult↗
PubMed1990

Classical conditioning and attentional bias.

The present study was designed to test whether an attentional bias can arise from aversive classical conditioning. Using a differential conditioning paradigm in which slides of angry faces served as conditioned stimuli (CS+/CS-) and electric shock served as unconditioned stimulus (UCS), skin conductance responses (SCRs) of normal subjects (N = 20) were recorded. The effectiveness of the conditioning procedure was proved by differential SCRs to CS+ and CS- slides during the later acquisition trials. During a subsequent extinction phase, sets of three numbers were superimposed on CS+ and CS- slides. subjects were asked to add up these numbers as quickly as possible and to vocalize the results. Vocalization latencies as indexed by chin EMG activity were significantly longer with CS+ than with CS- trials. This result is explained in terms of the attention attracting properties that the CS+ acquires as a result of its pairing with the UCS. It is argued that these properties compete with the attentional resources that are needed for an ongoing task (i.e., addition task). The data suggest that a learning approach to the origins of attentional biases in anxious subjects might be fruitful.

Adult↗
PubMed1977

Midbrain unit activity during classical conditioning.

In behaving rats, unit activity recorded from the ventral tegmentum and from the reticular formation was monitored during classical conditioning. Rewarding electric stimulation of the medial forebrain bundle was used as the unconditioned stimulus (UCS). Only those cells possessing prior responses to the conditioned stimulus (CS) changed their responses as a result of conditioning. Responses recorded from cells which were driven by both the auditory CS and the brain shock UCS were significantly more often changed than those driven by the CS alohe. These data show that the auditory and brain shock fields of influence interact in at least some brain regions prior to conditioning and that pairing the two kinds of stimuli is more likely to influence auditory responses recorded from these regions than those recorded elsewhere. It is possible to imagine that the intersection of the two fields is a sine qua non of conditioning and that the two prior actions caused the change by interacting at or near the recording point.

Action Potentials↗
PubMed1990

Classical conditioning induces CS-specific receptive field plasticity in the auditory cortex of the guinea pig.

To determine if classical conditioning produces general or specific modification of responses to acoustic conditioned stimuli (CS), frequency receptive fields (RF) of neurons in guinea pig auditory cortex were determined before and up to 24 h after fear conditioning. Highly specific RF plasticity characterized by maximal increased responses to the CS frequency and decreased responses to the pretraining best frequency (BF) and other frequencies was observed in 70% of conditioning cases. These opposing changes were often sufficient to produce a shift in tuning such that the frequency of the CS became the new BF. CS frequency specific plasticity was maintained as long as 24 h. Sensitization training produced general increased responses across the RF without CS specificity. The findings indicate that associative processes produce systematic modification of the auditory system's processing of frequency information and exemplify the advantages of combining receptive field analysis with behavioral training in the study of the neural bases of learning and memory.

Acoustic Stimulation↗
PubMed1983

Extinction and retention of a classically conditioned flexor nerve response in acute spinal cat.

These experiments were conducted to examine extinction and retention of a classically conditioned response in acute spinal cats. Conditioning was obtained by pairing a mild electrical stimulus to the superficial peroneal sensory nerve (CS) with a stronger electrical stimulus to the ankle skin (US) of the same leg. Subsequent extinction was produced by presenting CS-alone trials. In the first experiment, animals given massed extinction trials showed response decrements to base levels. Response decrements were not found in animals that received distributed extinction trials. In the second experiment, .5-, 1-, 2-, 3-, or 4-hr intervals between acquisition and extinction produced no significant differences in the extinction data. In the third experiment, animals received extinction trials immediately or 30 min after acquisition trials, followed by 20 additional extinction trials 30 min later. Analyses of these data indicated significant acquisition and extinction in the 10- and 20- acquisition trial groups. As in Experiment 2, varying the interval between acquisition and extinction did not produce any group differences in the extinction data. The results of these experiments demonstrate that response increases produced by paired trials in the spinal preparation do not decay spontaneously over time and are not caused by sensitization effects.

Animals↗
PubMed1997

Left hemisphere advantage for classical conditioning to auditory verbal CSs: effects of nonattended extinction.

The effects of brain laterality, or hemispheric asymmetry, on electrodermal classical conditioning during both attended and nonattended stimulus conditions were studied. Participants were conditioned to consonant-vowel (CV) syllables during an acquisition, or learning, phase of the experiment. During a subsequent extinction phase, the conditioned stimuli (CS) were presented in a dichotic mode of presentation. Half of the participants attended to the left ear (right hemisphere) during the extinction phase and the other half of the participants attended to the right ear (left hemisphere). The results showed effects of conditioning for all participants during the acquisition phase. During dichotic extinction, the left hemisphere group showed remaining learning effects in both the attended and nonattended conditions, whereas the right hemisphere group demonstrated conditioning only in the attended condition.

Acoustic Stimulation↗
PubMed1988

Learning in rats with caudate-putamen lesions: unimpaired classical conditioning and beneficial effects of redundant stimulus cues on instrumental and spatial learning deficits.

The effects of caudate-putamen lesions in the rat on conditioning were investigated in three experiments. In Experiment 1, rats with lesions were impaired on a spatial task that required learning to make the correct position response, but no deficit was obtained when the alternatives were differentiated by salient visual cues. Performance remained good even when the visual cues were removed. A classical conditioned suppression paradigm was used in Experiment 2, and caudate-putamen lesions were found not to impair acquisition of suppression or overshadowing. In Experiment 3 we revealed poor instrumental learning in subjects with lesions as retarded acquisition of lever-press responding and depressed variable interval response rates. When a light stimulus was present together with reinforced responses, response rates were depressed in the control group (which suggested an overshadowing phenomenon) but were potentiated in the group with lesions. The results showed that caudate-putamen lesions did not produce a general deficit in association formation. There was disruption of learning about responses but not stimuli and, moreover, it was found that redundant stimulus cues aided response learning. It appears that for normal subjects, the salience or associability of the response cues may largely determine the influence of stimuli presented during instrumental conditioning.

Animals↗
PubMed1996

Early acquisition, but not retention, of the classically conditioned eyeblink response is N-methyl-D-aspartate (NMDA) receptor dependent.

N-methyl-D-aspartate (NMDA) antagonists impair performance in some tasks, but whether they impair learning directly or through effects on sensorimotor performance remains controversial. Rats administered a competitive NMDA antagonist, CGP-39551, 24 hr before training could not acquire a classically conditioned eyeblink response. The associative deficit remained evident during training with a high-intensity conditioned stimulus, even though sensory reactivity was unaffected. The antagonist did not alter retention and thus did not affect motor performance of the task. These results extend and confirm studies that implicate NMDA-receptor activation in the acquisition of classically conditioned associations and specifically in tasks not dependent on the hippocampus for learning itself. Moreover, they substantiate recent claims that NMDA receptor activation (and by association, long-term potentiation) may be involved in early processes of procedural memory formation.

Animals↗
PubMed1997

Classical conditioning.

Evidence has amassed from research in humans indicating that the cerebellar circuitry serving as the substrate for eyeblink classical conditioning is similar to that in nonhuman primates. In patients with bilateral cerebellar lesions or neurodegenerative cerebellar disease, few conditioned eyeblink responses are produced with either the ipsilesional or the contralesional eye. Cerebellar patients with lateralized lesions, like rabbits with experimentally produced unilateral cerebellar lesions, produce relatively normal conditioned responses (CRs) with the contralesional eye and few or no CRs with the ipsilesional eye. Age-related deficits in eyeblink classical conditioning appear in humans and rabbits in middle age. In normal aging in many species, including humans, there is Purkinje cell loss in cerebellar cortex. In rabbits, the Purkinje cell number correlates highly with the rate of learning, regardless of age. Positron emission tomography imaging of normal young adults during eyeblink conditioning reveals changes in activity in the cerebellum. Timed interval tapping, a task that assesses cerebellar function, also predicts performance on eyeblink conditioning. In dual-task conditions involving simultaneous performance of eyeblink conditioning and timed interval tapping, eyeblink conditioning is impaired. Investigations of patients with lesions or neurodegenerative disease not involving the cerebellum demonstrate that acquisition of CRs is possible, although prolonged in the case of hippocampal cholinergic disruption. Evidence to date suggests that the human analogue of the rabbit interpositus nucleus, the globose nucleus, is essential for the production of the conditioned eyeblink response and that cerebellar cortical Purkinje cells play a role in normal acquisition.

Aging↗
PubMed1995

Intrauterine exposure to cocaine produces a modality-specific acceleration of classical conditioning in adult rabbits.

Previous studies had demonstrated that in utero exposure to cocaine produces structural changes in the development of the rabbit's anterior cingulate cortex. Because the anterior cingulate cortex has been proposed to subserve a variety of cognitive processes including associative learning, we investigated the effects of intrauterine exposure to cocaine on the acquisition of the rabbit's classically conditioned nictitating membrane response. Adult, sexually mature rabbits born of dams that had received intravenous injections of either saline or cocaine (4 mg/kg, twice a day) from day 8 to day 29 of gestation were classically conditioned by pairing tone and light CSs with an airpuff US. Rabbits that had been exposed to cocaine in utero demonstrated a more rapid acquisition of CRs to a tone CS but not to a light CS as compared with saline controls. Control experiments indicated that the accelerated learning to the tone CS was not due to sensitization, pseudoconditioning, altered baseline rate of responding, an increased responsiveness to the airpuff US, or to a change in the intensity threshold of the tone CS for elicitation of CRs. We conclude that in utero exposure to cocaine alters the processing of auditory stimuli and this leads to an abnormally rapid acquisition of CRs. It is suggested that this functional consequence of prenatal exposure to cocaine is due to structural abnormalities in anterior cingulate cortex.

Acoustic Stimulation↗
PubMed2000

Classical conditioning of responses to an artificial nipple in the rat fetus: mu and kappa opioid systems.

The rat fetus exhibits oral grasp responses when presented with an artificial nipple in utero. Preexposure to milk produces a transient decrease in oral grasp responses. The effect of milk on oral grasping is mediated by endogenous activity in brain opioid systems. Specifically, milk triggers mu activity in rostral brain regions and kappa opioid activity in caudal brain regions to decrease oral grasping of the artificial nipple. Reexposure to the artificial nipple after it has been paired with milk during a classical conditioning trial results in a conditioned reduction in oral grasping that is evident when fetuses are reexposed to the nipple. The classically conditioned decrease in oral grasping is mediated by mu opioid activity in rostral brain regions and kappa opioid activity in caudal brain regions. Endogenous opioid systems, activated by exposure to milk and the nipple, may regulate the processing of sensory information during suckling in the rat.

Animals↗