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)     

An associative process maintains reflex facilitation of the unconditioned nictitating membrane response during the early stages of training.

The presentation of a neutral or conditioned stimulus (CS) at an appropriate interval prior to the presentation of a corneal airpuff or a paraorbital shock (unconditioned stimulus, US) can facilitate the amplitude of the unconditioned nictitating membrane (NM) response in rabbits. In two experiments, it was demonstrated that an associative process mediates the maintenance of that facilitation during repeated CS–US pairings. Although CS-alone presentations produced a substantial decrease in the amount of reflex facilitation in animals not pretrained with the CS, pretraining that consisted of paired CS–US presentations prevented that decrease when CS-alone presentations were subsequently given. Conditioned facilitation of the unconditioned response occurred very rapidly (within 5–22 trials in these experiments) and long before the appearance of overt conditioned responses to the CS. In addition, it was demonstrated that conditioned facilitation can be relatively specific to the tonal frequency of the CS. These results indicate the first sign of conditioning of the NM response is exhibited in the amplitude of the unconditioned response. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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

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

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)     

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.     

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

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

Conditioning the unconditioned response: Modification of the rabbit's (Oryctolagus cuniculus) unconditioned nictitating membrane response.

Conditioning-specific reflex modification (CRM) occurs when classical conditioning modifies responding to a unconditioned stimulus/stimuli (UCS) in the absence of a conditioned stimulus (CS). Three experiments monitored rabbit (Oryctolagus cuniculus) nictitating membrane unconditioned responses to 5 intensities and 4 durations of periorbital electrical stimulation before and after CS or UCS manipulation. CRM occurred after 12 days of CS-UCS pairings but not following unpaired CS/UCS presentations or restraint. CRM survived CS-alone and CS/UCS-unpaired extinction of the conditioned response (CR) but not presentations of the UCS alone, although CRs remained intact. Thus, CRs could be weakened without eliminating CRM and CRM could be weakened without eliminating CRs. Data indicate CRM is a reliable, associative effect that is more than a generalized CR and may not be explained by habituation, stimulus generalization, contextual conditioning, or bidirectional conditioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampectomy disrupts auditory trace fear conditioning and contextual fear conditioning in the rat

The hippocampus is believed to be an important structure for learning tasks that require temporal processing of information. The trace classical conditioning paradigm requires temporal processing because the conditioned stimulus (CS) and the unconditioned stimulus (US) are temporally separated by an empty trace interval. The present study sought to determine whether the hippocampus was necessary for rats to perform a classical trace fear conditioning task in which each of 10 trials consisted of an auditory tone CS (1 5-s duration) followed by an empty 30-s trace interval and then a fear-producing floor-shock US (0.5-s duration). Several weeks prior to training, animals were anesthetized and given aspiration lesions of the neocortex (NEO; n = 6), hippocampus and overlying neocortex (HIPP; n = 7), or no lesions at all (control; n = 6). Approximately 24 h after trace conditioning, NEO and control animals showed a significant decrease in movement to a CS-alone presentation that was indicative of a conditioned fear response. Animals in the HIPP group did not show conditioned fear responses to the CS alone, nor did a pseudoconditioning group (n = 7) that was trained with unpaired CSs and USs. Furthermore, all groups except the HIPP group showed conditioned fear responses to the original context in which they received shock USs. One week later, HIPP, NEO, and control animals received delay fear-conditioning trials with no trace interval separating the CS and US. Six of seven HIPP animals could perform the delay version, but none could perform the trace version. This result suggests that the trace fear task is a reliable and useful model for examining the neural mechanisms of hippocampally dependent learning.     

Conditioning-specific reflex modification of the rabbit (Oryctolagus cuniculus) nictitating membrane response: Generality and nature of the phenomenon.

Conditioning-specific reflex modification (CRM) occurs when classical conditioning modifies responding to an unconditioned stimulus in the absence of a conditioned stimulus. This form of reflex modification suggests that learning modifies the unconditioned reflex pathway, Rabbit (Oryctolagus cuniculus) nictitating membrane responses to 5 intensities and 3 durations of airpuff (AP) or periorbital electrical stimulation (ES) were monitored before and after conditioning. AP tests detected strong CRM after conditioning with ES and modest levels of CRM after conditioning with AP. After conditioning with AP, ES tests failed to detect CRM. After conditioning with a stronger AP, CRM was again detected by AP tests. CRM is a general phenomenon but is more readily detected after training with a relatively aversive stimulus; thus, it may be a function of level of arousal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alteration of classically conditioned heart rate by operant reinforcement in monkeys.

Ran 6 adolescent male rhesus monkeys alternately on classical conditioning and on operant heart rate training schedules. The classical unconditioned stimulus (UCS) was identical to the operant negative reinforcement. After operant training, some Ss changed their heart rate responses to the classical conditioned stimulus (CS). When both the operant and the classical schedules were in force simultaneously, all Ss changed their previous heart rate responses to the classical CS without significantly changing their blood pressure responses to this stimulus. The changes in heart rate response to the CS sometimes persisted long after the operant schedules were no longer in force. These results show that a classically conditioned response can be altered by operant reinforcement, and they suggest that the classical UCS actually may be an operant reinforcer. (29 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of stimulus modality and task condition on blink startle modification and on electrodermal responses

Participants in Experiments 1 and 2 performed a discrimination and counting task to assess the effect of lead stimulus modality on attentional modification of the acoustic startle reflex. Modality of the discrimination stimuli was changed across subjects. Electrodermal responses were larger during task-relevant stimuli than during task-irrelevant stimuli in all conditions. Larger blink magnitude facilitation was found during auditory and visual task-relevant stimuli, but not for tactile stimuli. Experiment 3 used acoustic, visual, and tactile conditioned stimuli (CSs) in differential conditioning with an aversive unconditioned stimulus (US). Startle magnitude facilitation and electrodermal responses were larger during a CS that preceded the US than during a CS that was presented alone regardless of lead stimulus modality. Although not unequivocal, the present data pose problems for attentional accounts of blink modification that emphasize the importance of lead stimulus modality.     

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)     

Motor cortex lesions do not affect learning or performance of the eyeblink response in rabbits.

The possible modulatory role of motor cortex in classical conditioning of the eyeblink response was examined by ablating anterior neocortex in rabbits and training them with an auditory conditioned stimulus (CS) and an airpuff unconditioned stimulus (US) in either a delay (Experiment 1) or a trace (Experiment 2) conditioning paradigm. Topographic measures such as amplitude and onset latency were assessed during conditioning sessions for conditioned responses (CRs) and on separate test days for unconditioned responses (URs) by using a range of US intensities. No lesion effects were observed for learning or performance measures in acquisition or retention of either delay or trace conditioning. During trace conditioning, lesioned rabbits did, however, exhibit a trend toward impairment and demonstrated significantly longer CR latencies. Damage to motor and frontal cortex does not significantly affect eyeblink response performance or learning in either a delay or a trace conditioning paradigm. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Bilateral cerebellar lesions disrupt conditioned eyelid responses in unrestrained rats.

Electromyographic eyelid responses in unrestrained rats were classically conditioned in a Pavlovian delay paradigm by using a tone conditioned stimulus (CS) and periorbital shock unconditioned stimulus (US). After eyelid conditioning was complete, bilateral electrolytic lesions were made in the dentate-interpositus region of the cerebellar nuclei. Initial eyelid conditioning was reliable and very similar to that previously observed in the rabbit, although the asymptotic eyelid responses contained a short-latency startle response in addition to the usual conditioned and unconditioned responses (CR and UR). Substantial decrements in CRs were observed in 13 of the 14 rats with accurately placed lesions. In contrast, startle responses and URs were unaffected. Results replicate the effects of cerebellar lesions on eyelid CRs in the rabbit and suggest that the anatomical basis of eyelid conditioning in both species is similar. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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

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

Mechanism of the radiation-protective effect of indralin

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

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)     

Stimulation at a site of auditory-somatosensory convergence in the medial geniculate nucleus is an effective unconditioned stimulus for fear conditioning.

The medial division of the medial geniculate nucleus (MGm) and the posterior intralaminar nucleus (PIN) are necessary for conditioning to an auditory conditioned stimulus/stimuli (CS), receive both auditory and somatosensory input, and project to the amygdala, which is involved in production of fear conditioned responses (CRs). If CS–unconditioned stimulus (UCS) convergence in the MGm-PIN is critical for fear conditioning, then microstimulation of this area should serve as an effective UCS during classical conditioning, in place of standard footshock. Guinea pigs underwent conditioning (40–60 trials) using a tone as the CS and medial geniculate complex microstimulation as the UCS. Conditioning bradycardia developed when the UCS electrodes were in the PIN. However, microstimulation was not an effective UCS for conditioning in other parts of the medial geniculate or for sensitization training in the PIN or elsewhere. Learning curves were similar to those found previously for footshock UCS. Thus, the PIN can be a locus of functional CS–UCS convergence for fear conditioning to acoustic stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Failure of hippocampectomy to facilitate classical conditioning at an optimal interstimulus interval is not due to a "ceiling effect."

Examined the effects of amphetamine injection (2 mg/kg), hippocampal lesions, and cortical lesions in 30 naive New Zealand albino rabbits during classical conditioning of the rabbit nictitating membrane response. An optimal interstimulus interval (ISI) was employed. Whereas neocortical and hippocampal damage had no significant effect on the rate of acquisition, amphetamine treatment produced a marked facilitation. A control group of amphetamine-treated Ss receiving explicitly unpaired presentations of the conditioned stimulus/stimuli (CS) and unconditioned stimulus/stimuli (UCS) failed to exceed spontaneous response rates throughout training. The failure of hippocampectomy to accelerate conditioning under an optimal ISI does not appear to be due to a ceiling effect. Rather, it is suggested that the response system is predisposed to conditioned responses of a given latency. Optimal ISIs may fall within this range. Thus, in short or long intervals, temporal aspects of the motor response must be adjusted to conform to the stimulus configuration. It appears that the hippocampus is a likely source of response modulation. Thus, loss of hippocampal input accelerates conditioning under nonoptimal intervals at the expense of proper timing. Conditioning under an optimal interval would occur at normal rates because no modulation is required. (19 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)