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)     

Abnormal topography and altered acquisition of conditioned eyeblink responses in a rodent model of attention-deficit/hyperactivity disorder.

The spontaneously hypertensive rat (SHR) has been suggested as a possible animal model of attention-deficit/hyperactivity disorder (ADHD). Reductions in the volume of the cerebellum and impairments in cerebellar-dependent eyeblink conditioning have been observed in ADHD, prompting investigation into whether SHRs also exhibit eyeblink conditioning impairments. In Experiment 1, SHRs and a control strain, Wistar, were trained on a long-delay eyeblink conditioning task in which a tone conditioned stimulus was paired with a periorbital stimulation unconditioned stimulus (750-ms delay paradigm). SHRs exhibited faster acquisition of eyeblink conditioned responses (CRs) and displayed mistimed (early onset and peak latency) and larger CRs in comparison with Wistar rats. In subsequent extinction training, SHRs were slower to extinguish CRs. The authors conducted Experiment 2 using separate rats to rule out the possibility that the results of Experiment 1 were due to nonassociative responding. SHRs and Wistar rats were presented with explicitly unpaired tone and periorbital stimulation stimuli. There was no evidence of conditioning in either group, nor were there differences between the groups in terms of the number of eyeblink responses elicited by the tone. The current results support the hypothesis of cerebellar abnormalities in this rodent model of ADHD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Classical eyeblink conditioning in two strains of mice: Conditioned responses, sensitization, and spontaneous eyeblinks.

Conditioned eyeblink responses (CRs), sensitization, and spontaneous eyeblinks were studied in C57BL/6J and BALB/c mice. Both strains of mice acquired CRs during 10 days of classical delay eyeblink conditioning. The BALB/c mice reached a higher asymptotic CR level than the C57BL/6J mice. The CRs were extinguished and recovered in both strains following conditioned stimulus-alone and paired conditioned stimulus-unconditioned stimulus training. During 10 days of explicitly unpaired training, the control groups showed no signs of sensitization and low incidence of spontaneous eyeblinks. When switched to paired training, the unpaired groups exhibited significant conditioned inhibition. These results suggest that strain differences must be considered in experimental design and data interpretation for these basic aspects of associative learning and memory. (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.     

Nicotinic cholinergic system involvement in eyeblink classical conditioning in rabbits.

A nicotinic cholinergic antagonist, mecamylamine (MEC), was administered to rabbits tested on eyeblink classical conditioning (EBCC) in the 750-msec delay paradigm for 10 90-trial sessions. Nicotinic receptors were measured in 3 brain regions in S treatment groups: paired conditioned stimulus–unconditioned stimulus (CS–UCS) presentations with (1) vehicle, young; (2) vehicle, older; (3) 0.5 mg/kg MEC, young; unpaired CS–UCS with (4) 0.5 mg/kg MEC, young; and (5) vehicle, young. Daily MEC injections disrupted acquisition in young rabbits (769 trials to learning criterion vs 323 trials for vehicle-treated young rabbits). MEC-treated young rabbits learned similarly to older rabbits. Brain nicotinic receptors were not affected by 10 daily MEC injections. To our knowledge, this experimental protocol, using a low MEC dose to selectively inhibit nicotinic cholinergic receptors, is the first to demonstrate a role for nicotinic cholinergic receptors in EBCC. (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)     

Training to criterion in eyeblink classical conditioning in Alzheimer's disease, Down's syndrome with Alzheimer's disease, and healthy elderly.

The cholinergic antagonist scopolamine delays acquisition of eyeblink classical conditioning (EBCC) in rabbits and humans, but scopolamine-treated organisms eventually acquire conditioned responses (CRs). Patients with probable Alzheimer's disease (AD) and older adults with Down's syndrome (DS/AD) have disrupted cholinergic systems and perform EBCC very poorly. It was hypothesized that patients with probable AD and DS/AD, like scopolamine-injected organisms, would acquire CRs if given sufficient training. Twelve probable AD patients, 12 DS/AD patients, and 6 healthy elderly control individuals participated in 5 daily 90-trial sessions of EBCC. Fifty-eight percent of the probable AD, 92% of the DS-AD, and 100% of the control participants achieved learning criterion. Probable AD, DS/AD, and control participants had statistically significant increases in the percentage of CRs produced over 5 EBCC sessions. The neural substrate for EBCC was not eliminated in probable AD or DS/AD patients, although the learning mechanism was disrupted. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Temporal discrimination learning in severe amnesic patients reveals an alteration in the timing of eyeblink conditioned responses.

This study investigated whether the hippocampal system plays a modulatory role in the timing of conditioned responses (CRs) in eyeblink classical conditioning. Seven bitemporal amnesic patients and 7 controls were randomly presented 2 tone conditioned stimuli (CSs) that were individually paired with two different interstimulus intervals (ISIs) in a delay conditioning task. It was found that amnesic patients' CRs occurred significantly earlier than control participants' CRs at the longer ISI. Amnesic patients also produced significantly more nonadaptive CRs than did control participants, their level of acquisition was less than that of control participants after equating for ISI, and they did not show extinction with the longer ISI. These data suggest a role of the hippocampal system in controlling the precise timing of conditioned eyeblink responses and in acquiring and extinguishing responses within the context of a temporal discrimination task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuronal activity in the medial prefrontal cortex during Pavlovian eyeblink and nictitating membrane conditioning

The present study assessed Pavlovian eyeblink (EB) conditioning, using tones and periorbital shock as the conditioned and unconditioned stimuli (CS and US), and nictitating membrane (NM) conditioning, using tones and airpuffs as the CS and US. During each experiment, CS-evoked changes in multiple-unit activity (MUA) in the medial prefrontal cortex (mPFC) were recorded. Concomitant heart rate (HR) conditioned responses (CRs) were also recorded. A nonassociative control group received explicitly unpaired presentations of the CS and US in each experiment. Increases in both NM and EB CRs occurred over sessions in the paired, but not the unpaired, groups. Decelerative HR CRs also occurred in the eyeshock, but not the airpuff, group. Although tone-evoked increases in neuronal activity were obtained during 10 initial tone-alone presentations in all groups, this activity habituated over trials. CS-evoked increases in neuronal activity also occurred, but this activity was considerably greater in the group that received periorbital shock as the US. During subsequent extinction trials, decreases in tone-evoked neuronal activity occurred in this group, compared with the previous CS/US paired trials. CS-evoked MUA increases were minimal during all except the pretraining phase of the study in the CS/US unpaired control groups and in the paired airpuff group. These findings show that neuronal activity during associative learning occurs in the mPFC during Pavlovian EB, as well as HR conditioning, but this activity apparently reflects an affective component to learning that is only indirectly related to skeletal conditioning.     

Larger nondeclarative than declarative deficits in learning and memory in human aging.

This study used classical conditioning as a measure of nondeclarative learning and compared it with verbal learning as a declarative measure. Eighty participants were tested using 1 of 2 paradigms (400-ms and 750-ms delay) for eyeblink classical conditioning (EBCC) and the California Verbal Learning Test (CVLT). Large age differences were observed in the nondeclarative EBCC task, even in the 750-ms paradigm, which is more optimal for older adults. Age differences in the nondeclarative EBCC task were larger in the 400-ms paradigm and equal in the 750-ms paradigm to the magnitude of age differences in the declarative CVLT task. Partial correlations (removing the variance that was due to age) showed no relation between performance on the nondeclarative and declarative tasks. The results contradict the common assumption that, in the same participants, nondeclarative learning and memory are more resistant to the effects of aging than are declarative learning and memory and suggest that nondeclarative learning and memory are not unitary. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquired appetitive responding to intravenous nicotine reflects a Pavlovian conditioned association.

Recent research examining Pavlovian appetitive conditioning has extended the associative properties of nicotine from the unconditioned stimulus or reward to include the role of a conditional stimulus (CS), capable of acquiring the ability to evoke a conditioned response. To date, published research has used presession extravascular injections to examine nicotine as a contextual CS in that appetitive Pavlovian drug discrimination task. Two studies in the current research examined whether a nicotine CS can function discretely, multiple times within a session using passive iv infusions. In Experiment 1, rats readily acquired a discrimination in conditioned responding between nicotine and saline infusions when nicotine was selectively paired with sucrose presentations. In Experiment 2, rats were either trained with nicotine paired with sucrose or explicitly unpaired with sucrose. The results showed that rats trained with explicitly unpaired nicotine and sucrose did not increase dipper entries after the infusions. Nicotine was required to be reliably paired with sucrose for control of conditioned responding to develop. Implications of these findings are discussed in relation to tobacco addiction, learning theory, and pharmacology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Eyeblink classical conditioning in Down's syndrome, Fragile X syndrome, and normal adults over and under age 35.

44 adults with Down's syndrome (DS), 20 adults with Fragile X syndrome (FX), and 44 normal control (NC) Ss performed eyeblink classical conditioning (EBCC) in a 400-msec delay paradigm. Adults with DS older than 35 yrs (ODS) were significantly impaired relative to younger adults with DS (YDS), adults with FX, and NCs. ODSs conditioned comparably to Alzheimer's disease (AD) patients. The DS mental status examination and the Vineland Adaptive Behavior Scales did not differentiate ODSs from YDSs. YDSs scored higher than ODSs on the Slosson Intelligence Test, but the difference was not clinically significant. Because ODSs had lower blink amplitudes, their poor EBCC could result from peripheral factors. YDSs conditioned similarly to older NCs and worse than their age-matched NCs. Younger and older adults with FX conditioned as well as young NCs. EBCC identified accelerated aging in YDSs and may detect AD neuropathology in ODSs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

CS-US preexposure effects on trace eyeblink conditioning in young rats: Potential implications for functional brain development.

Recent studies of delay eyeblink conditioning (EBC) in young rats have demonstrated different effects of various conditioned and unconditioned stimulus (CS-US) preexposure conditions on learning at different ages. The present study extends this research to trace EBC. Subjects experienced 1 of 3 preexposure conditions (paired CS-US, unpaired CS-US, or no stimuli) at either 20 or 24 days of age. Four days later, they were conditioned using either trace (Experiment 1) or delay (Experiment 2) EBC parameters. Results were similar at both ages tested. Paired preexposure facilitated acquisition of delay but not trace relative to context preexposure. Unpaired preexposure impaired acquisition of both delay and trace. These behavioral findings provide a foundation for hypotheses about the functional maturation of cerebellar, hippocampal, and entorhinal learning circuits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ontogeny of the conditioned eyeblink response in rats: acquisition or expression?

Eyeblink conditioning depends critically on an identified brainstem-cerebellar circuit and is modulated under some circumstances by the hippocampus, amygdala, and other forebrain regions. Developmental studies of eyeblink conditioning could help elucidate questions concerning the behavioral expression of plasticity within these brain circuits and regions, and of their functional interactions, as they unfold during ontogeny. Recently, this laboratory has shown that conditioning of the eyeblink reflex develops dramatically between Postnatal Days (PND) 17 and PND 24 in the rat. The present study asked whether the developmental emergence of the eyeblink conditioned response (CR) occurs gradually or abruptly over this age range, and whether it reflects developmental changes in acquisition or expression of the learned eyeblink reflex. In Experiment 1, rat pups received two consecutive days of training beginning on PND 17, 20, or 24. Conditioned responses occurred at low levels on PND 17-18, intermediate levels on PND 20-21, and high levels on PND 24-25. In Experiment 2, 17-day-old rats received 2 days of training, 72 h apart, so that effects of training on PND 17 could be examined at an age, PND 20, when expression of the eyeblink CR was clearly possible. On PND 20, rat pups that had received paired training on PND 17 showed significantly faster conditioning than controls that had received unpaired training or no training on PND 17. These findings suggest that neural plasticity underlying associative learning developmentally precedes its overt expression in behavior. Hypotheses concerning the nature and locus of this learning are discussed.     

Exposure to inescapable stress persistently facilitates associative and nonassociative learning in rats.

The present study examined the proactive effects of inescapable stress on aversive Pavlovian conditioning. Stressed rats were restrained and exposed to 90 1-mA tailshocks. Twenty-four hours later, all rats were exposed to 10 conditioned stimuli (CS; 350 ms of white noise at 85 dB). Rats then received either paired training in which the CS coterminated with a 100-ms, 0.7-mA periorbital shock or the same stimuli presented in an explicitly unpaired fashion. After the unpaired exposures, these rats were also exposed to paired training. Previously stressed rats exhibited persistent sensitization to the white-noise stimulus. Stressed rats exposed to unpaired stimuli, and no longer exhibiting a sensitized response, acquired the eyeblink conditioned response at a facilitated rate when these stimuli were presented in a paired fashion. These results also demonstrate that the effect of stress on classical conditioning is long-lasting, in excess of 48 hr. (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)     

Competition between novelty and cocaine conditioned reward is sensitive to drug dose and retention interval.

The conditioned rewarding effects of novelty compete with those of cocaine for control over choice behavior using a place conditioning task. The purpose of the present study was to use multiple doses of cocaine to determine the extent of this competition and to determine whether novelty’s impact on cocaine reward was maintained over an abstinence period. In Experiment 1, rats were conditioned with cocaine (7.5, 20, or 30 mg/kg ip) to prefer one side of an unbiased place conditioning apparatus relative to the other. In a subsequent phase, all rats received alternating daily confinements to the previously cocaine paired and unpaired sides of the apparatus. During this phase, half the rats had access to a novel object on their initially unpaired side; the remaining rats did not receive objects. The ability of novelty to compete with cocaine in a drug free and cocaine challenge test was sensitive to cocaine dose. In Experiment 2, a place preference was established with 10 mg/kg cocaine and testing occurred after 1, 14, or 28 day retention intervals. Findings indicate that choice behaviors mediated by cocaine conditioning are reduced with the passing of time. Taken together, competition between cocaine and novelty conditioned rewards are sensitive to drug dose and retention interval. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acquisition of Differential Delay Eyeblink Classical Conditioning Is Independent of Awareness.

There has been debate about whether differential delay eyeblink conditioning can be acquired without awareness of the stimulus contingencies. In 4 experiments, the authors reexamined this question. Older participants were tested with a tone and white noise (Experiment 1) or with 2 tones (Experiment 2). In addition, younger participants were tested with 2 tones (Experiment 3) or with 2 tones plus the parameters from an earlier study that had reported a relationship between conditioning and awareness (Experiment 4). Participants who were designated aware of the stimulus contingencies and participants who were designated unaware exhibited equivalent levels of differential eyeblink conditioning. Awareness of stimulus contingencies is not required for differential delay eyeblink conditioning when simple conditioned stimuli are used. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Eyeblink Classical Conditioning to Auditory and Olfactory Stimuli: Performance Among Older Adults With and Without the Apolipoprotein E ε4 Allele.

Patients with Alzheimer's disease (AD) demonstrate slowed acquisition of the conditioned response (CR) in eyeblink classical conditioning paradigms (EBCC), although it is unknown how early in the course of the disease CR acquisition is affected. This study investigated whether changes in the rate of CR acquisition were apparent in nondemented older adults at greater genetic risk for developing AD (i.e., carriers of the apolipoprotein E [APOE] ε4 allele). Both ε4+ and ε4- participants demonstrated CR acquisition to auditory and olfactory CSs; however, rate of acquisition to the olfactory CS was significantly slower in ε4+ persons. Both groups acquired the CR to an auditory CS at the same rate. Results support olfactory compromise in the earliest stages of the AD disease process. (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)