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

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

Age-related deficits in retention of the classically conditioned nictitating membrane response in rabbits.

Young and aged rabbits underwent classical conditioning of the nictitating membrane response (NMR) to a tone conditioned stimulus (CS) and a corneal airpuff unconditioned stimulus (UCS) for 18 consecutive days. Rabbits were then returned to their home cages for a 90-day period in which they received no further conditioning, but they were handled daily. On Day 91 they underwent retention testing during which the CS alone was presented 20 times. This was immediately followed by reacquisition in which the CS and UCS were again paired for 100 trials. Reacquisition was repeated on the following day. As in previous studies, aged rabbits acquired the conditioned response (CR) more slowly than young rabbits; however, by the end of acquisition, both groups reached similar asymptotic levels. Retention of the CR was significantly lower for aged than young rabbits. Reacquisition was also retarded in aged vs young rabbits. Nonassociative factors, such as sensitivity to the stimuli or general health, could not account for these differences. Data are discussed in terms of using retention of the conditioned eyeblink response as a model system for studying age-related memory deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of amygdala lesions on reflex facilitation and conditioned response acquisition during nictitating membrane response conditioning in rabbit.

Demonstrated that large lesions of the amygdala disrupt the maintenance of reflex facilitation of the unconditioned nictitating membrane (NM) response and slow the acquisition of conditioned NM responses in rabbits. Before behavioral training, the central nucleus of the amygdala and adjacent areas were lesioned electrolytically. In Exp 1, the lesioned animals exhibited no reflex facilitation of the unconditioned NM response at conditioned stimulus (CS)–unconditioned stimulus (UCS) intervals of 125–8,000 ms. In Exps 2 and 3, in which 1 CS–UCS interval (500 ms) was used, the lesions disrupted the maintenance of reflex facilitation but did not alter the facilitation exhibited in the 1st block of training. The lesions retarded the acquisition of conditioned NM responses when the 1,000-Hz tone CS intensity was 65 dB, but not when the intensity was 85 dB. (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)     

Lesions of the cerebellar vermis and cerebellar hemispheres: Effects on heart rate conditioning in rats.

The effects of lesions of the cerebellum on the acquisition of heart rate (HR) conditioned responses (CRs) were examined in rats. Large lesions of the cerebellar vermis severely attenuated the acquisition of differentially conditioned bradycardic responses in restrained rats without affecting unconditioned HR responses to the tone conditioned stimuli (CSs) or the shock unconditioned stimulus/stimuli (UCS). In Exp 2, Ss were trained unrestrained, and under these conditions the CR was tachycardia in control Ss. Lesions of the vermis again severely attenuated acquisition of this CR without affecting unconditioned response (UCR) to the CSs or UCS. Bilateral lesions of the cerebellar hemispheres did not affect HR conditioning in either test procedure. The vermis of the cerebellum is an essential component of an HR conditioning circuit in the rat. The cerebellar hemispheres, which are involved in some discrete somatomotor CRs, have no essential functional contribution to HR conditioning. Results are discussed in relation to contributions from a forebrain system involved in HR conditioning and in relation to lateral cerebellar contributions to discrete somatomotor CRs. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Aluminum-induced neurofibrillary degeneration disrupts acquisition of the rabbit's classically conditioned nictitating membrane response.

Rabbits received intraventricular injections of aluminum chloride, hydrochloric acid, or served as unoperated controls. On the 6th day postsurgery, they underwent 4 days (100 trials per day) of classical conditioning of the nictitating membrane response (NMR) to a tone conditioned stimulus and an air-puff unconditioned stimulus. Unoperated and hydrochloric acid control animals readily acquired the conditioned response. Aluminum intoxicated rabbits, in contrast, did not acquire the conditioned response over the 4 days of testing. This disruption of conditioning in aluminum-treated rabbits could not be attributed to deficits in sensory or motor processes or to illness. Neuropathological analysis revealed widespread neurofibrillary tangle formation in aluminum-treated animals. Furthermore, the degree of neurofibrillary degeneration was significantly negatively correlated with the degree of conditioning. The results are considered in the context of using the rabbit NMR preparation as a model system for studying age-related conditioning disorders. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Overshadowing and summation in compound stimulus conditioning of the rabbit's nictitating membrane response.

Examined acquisition of the rabbit's nictitating membrane response to a light?+?tone simultaneous compound stimulus and its components as a function of the intensity of the tone. In Exp I, the tone intensity was varied across the values of 85, 89, and 93 db, and the CS–UCS interval was 400 msec. In Exp II, the tone intensities were 73, 85, and 93 db, and the CS–UCS interval was 800 msec. Exps III and IV further examined the effects of the 73-db CS–UCS tone at CS–UCS intervals of 400 and 800 msec. All experiments included control groups, which were trained with either a light or a tone CS. Overall results show repeated instances of overshadowing: the impairment of CR acquisition to one or both of the components of a compound. Two types of summation were obtained: within-Ss summation, in which Ss trained with a compound showed a higher level of responding to the compound than to either of its component CSs; and between-groups summation, in which a group trained with a compound showed faster CR acquisition than either of its corresponding control groups trained with a single CS. Results are discussed in terms of perceptual and distributive processing models of compound stimulus conditioning. (37 ref) (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)     

Classical conditioning after cerebellar lesions in humans.

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

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

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

CS–US contiguity and CS intensity in conditioning of the rabbit's nictitating membrane response to serial compound stimuli.

Two experiments examined 48 female albino rabbits' nictitating membrane response to serial-compound stimuli consisting of 2 distinctive CSs (CSA and CSB) that were followed by a shock UCS. In Exp I, CSA was a highly salient 93-db tone, and CSB was a moderately salient flashing light. The CSA/UCS interval was 800 msec, and the CSB/UCS interval was varied across 400, 600, and 800 msec. In Exp II, the flashing light served as CSA, and CSB was either a 73-, 85-, or 93-db tone. The CSA/UCS interval remained 800 msec, and the CSB/UCS interval was fixed at 400 msec. The CSB/UCS interval and CSB intensity determined the rate of CR acquisition to the compound. Yet, CR acquisition to CSB showed impairments relative to the level of responding in single CS-control conditions. However, the impairment in CR acquisition to CSB was attenuated by increasing CSB/UCS contiguity. The impairment in acquisition to the light CSB appeared to be primarily a consequence of the tone CSA's greater salience. However, impairments in CR acquisition to CSB appeared even when CSB had the combined advantages of CS/UCS contiguity and great salience relative to CSA. Results indicate a role for CSA's temporal primacy in determining CR acquisition to the components of a serial compound and are discussed in terms of selective-attention, generalization-decrement, and information hypotheses. (45 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of the hippocampus in blocking and conditioned inhibition of the rabbit's nictitating membrane response.

In Exp I, bilateral aspiration of the dorsal hippocampus produced a disruption of blocking of 30 New Zealand rabbits' nictitating membrane response in L. J. Kamin's (1968, 1969) 2-stage paradigm, but had no effect on the formation of a Pavlovian conditioned inhibitor in Exp II (27 Ss). Results of Exp I indicate that normal Ss and those with cortical lesions given conditioning to a light-plus-tone CS gave CRs to both light and tone during nonreinforced presentations of each (test phase). If, however, compound conditioning was preceded by tone acquisition, only the tone elicited a CR during testing; that is, blocking was observed. In Ss with hippocampal lesions, however, CRs were given to both light and tone during testing whether or not compound conditioning was preceded by tone acquisition. Data from Exp II show that Ss with hippocampal lesions could discriminate as well as normal Ss and those with cortical lesions between a light (CS+) and light plus tone (CS-). In addition, when the inhibitory tone was subsequently paired with the UCS in retardation testing, Ss in all 3 lesion conditions acquired the CR at the same rate. Thus, it appears that hippocampal lesions do not disrupt conditioned inhibition. Results are taken as support for the view that the hippocampus is responsible for "tuning out" stimuli that have no adaptive value to the organism. (27 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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)     

Effects of morphine, ethylketocyclazocine, and N-allylnormetazocine on classical conditioning of the rabbit nictitating membrane response.

The nictitating membrane response of 120 New Zealand albino rabbits was classically conditioned to tone and light conditioned stimuli (CSs) presented for 800 msec before delivery of a 100-msec unconditioned shock stimulus. Both the mu receptor agonist morphine (5 mg/kg) and the kappa receptor agonist ethylketocyclazocine (1 mg/kg) significantly retarded the acquisition of conditioned responses (CRs). The retardant effects of both morphine and ethylketocyclazocine on CR acquisition could still be detected when the Ss were tested 5 days after cessation of drug injections. The sigma receptor agonist N-allylnormetazocine (5 mg/kg) had no effect on acquisition. The retardant effects of morphine and ethylketocyclazocine on acquisition were significantly antagonized by both naloxone (1 mg/kg) and N-allylnormetazocine. It is suggested that mu and possibly kappa receptors are involved in the retardant effects of opiates on CR acquisition. (14 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impact of continuous versus intermittent CS-UCS pairing on human brain activation during Pavlovian fear conditioning.

During Pavlovian fear conditioning a conditioned stimulus (CS) is repeatedly paired with an aversive unconditioned stimulus (UCS). In many studies the CS and UCS are paired on every trial, whereas in others the CS and UCS are paired intermittently. To better understand the influence of the CS-UCS pairing rate on brain activity, the experimenters presented continuously, intermittently, and non-paired CSs during fear conditioning. Amygdala, anterior cingulate, and fusiform gyrus activity increased linearly with the CS-UCS pairing rate. In contrast, insula and left dorsolateral prefrontal cortex responses were larger during intermittently paired CS presentations relative to continuously and non-paired CSs. These results demonstrate two distinct patterns of activity in disparate brain regions. Amygdala, anterior cingulate, and fusiform gyrus activity paralleled the CS-UCS pairing rate, whereas the insula and dorsolateral prefrontal cortex appeared to respond to the uncertainty inherent in intermittent CS-UCS pairing procedures. These findings may further clarify the role of these brain regions in Pavlovian fear conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Emotional Conditioning to Masked Stimuli and Modulation of Visuospatial Attention.

Two studies investigated the effects of conditioning to masked stimuli on visuospatial attention. During the conditioning phase, masked snakes and spiders were paired with a burst of white noise, or paired with an innocuous tone, in the conditioned stimulus (CS)+ and CS- conditions, respectively. Attentional allocation to the CSs was then assessed with a visual probe task, in which the CSs were presented unmasked (Experiment 1) or both unmasked and masked (Experiment 2), together with fear-irrelevant control stimuli (flowers and mushrooms). In Experiment 1, participants preferentially allocated attention to CS+ relative to control stimuli. Experiment 2 suggested that this attentional bias depended on the perceived aversiveness of the unconditioned stimulus and did not require conscious recognition of the CSs during both acquisition and expression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditioned diminution of the unconditioned skin conductance response.

During Pavlovian conditioning the expression of a conditioned response typically serves as evidence that an association between a conditioned stimulus (CS) and an unconditioned stimulus (UCS) has been learned. However, learning-related changes in the unconditioned response (UCR) produced by a predictable UCS can also develop. In the present study, we investigated learning-related reductions in the magnitude of the unconditioned skin conductance response (SCR). Healthy volunteers participated in a differential conditioning study in which one tone (CS+) was paired with a loud white-noise UCS and a second tone (CS?) was presented alone. In addition, probe trials that consisted of UCS presentations paired with the CS+ (CS + UCS) and CS? (CS ? UCS), as well as presentations of the UCS alone were included to assess UCR diminution. SCR and participants' expectations of UCS presentation were monitored during conditioning. Greater diminution of the UCR was observed to the UCS when it followed the CS+ compared to when it followed the CS? or was presented alone. Further, UCR amplitude showed an inverse relationship with the participants' ratings of UCS expectancy. However, conditioned UCR diminution was also observed independent of differential UCS expectancies. Our findings demonstrate conditioned diminution of the unconditioned SCR. Further, these findings suggest that although UCR amplitude is modified by conscious expectations of the UCS, conditioned diminution of the UCR can be expressed independent of learning-related changes in these expectations. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Discriminative conditioning with different CS–US intervals produces temporally differentiated conditioned responses in the two eyes of the rabbit (Oryctolagus cuniculus).

The conditioned eyeblink response (CR) in rabbits is lateralized to the eye targeted by the unconditioned stimulus (US). However, a contralateral component has been reported during concurrent discriminative conditioning of the two eyes. The authors investigated CRs produced by both eyes during conditioning with 2 different interstimulus intervals (ISIs) in which a short conditioned stimulus (CS) was paired with a US to the left eye and a long CS was paired with a US to the right eye. Whether the 2 CSs were more or less similar (or identical), the short CS produced short-latency CRs in the left eye, whereas the long CS produced long-latency CRs in the right eye. The contralateral responses to a CS trained at one ISI were separable into temporal corollaries of the ipsilateral response (suggesting a bilaterality of the CR) versus those to a CS trained at another ISI (indicating generalization between the CSs). The results indicate that the neuronal substrates subserving CRs of the two eyes involve not only a dominant lateralization but also some avenue of bilaterality. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Autonomic-somatic interaction and hippocampal theta activity.

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

Amygdalar Lateralization in Fear Conditioning: Evidence for Greater Involvement of the Right Amygdala.

The relative contribution of left and right amygdalae in the acquisition and retention of fear conditioning was investigated in rats. Pretraining bilateral electrolytic lesions blocked the acquisition of conditioned fear to tone and context, whereas unilateral lesions induced partial impairments with no left-right amygdala differences. In contrast, posttraining bilateral and unilateral lesions produced significant deficits in the retention of conditioned fear to tone and context. Although no left-right difference was observed to tone, the right amygdala lesions generated greater deficits in contextual fear than the left amygdala lesions. These results indicate that fear conditioning is partially disrupted with unilateral amygdalar lesions, but that the right amygdala has greater involvement than the left amygdala when conditioning occurs under a normal brain state. (PsycINFO Database Record (c) 2010 APA, all rights reserved)