Medial prefrontal lesions attenuate conditioned reflex facilitation but do not affect prepulse modification of the eyeblink reflex in rabbits

Conditioned reflex facilitation occurs when the amplitude of the eyeblink (EB) unconditioned reflex (UR) is increased as a result of prior pavlovian conditioning. Prepulse modification of the EB reflex is produced by preceding the unconditioned stimulus (US) by a brief low-level neutral stimulus. This study examined both conditioned EB facilitation and prepulse modification in rabbits with either medial prefrontal (mPFC) lesions or sham lesions. Conditioned reflex facilitation was assessed by comparing EB UR amplitude prior to and after pavlovian EB conditioning. Animals that received CS/US paired presentations showed evidence of conditioned reflex facilitation, but animals with unpaired training did not. However, this increase in EB UR magnitude in the paired groups was smaller in animals with mPFC lesions, compared to those with sham lesions. In two subsequent experiments different groups of sham and lesion animals received an intense burst of white noise preceded by tones with different interstimulus interval durations to assess prepulse modification. Unlike conditioned facilitation, prepulse modification was unaffected by mPFC lesions.     

Spontaneous recovery but not reinstatement of the extinguished conditioned eyeblink response in the rat

Reinstatement--the return of an extinguished conditioned response (CR) after reexposure to the unconditioned stimulus (US)--and spontaneous recovery--the return of an extinguished CR with the passage of time--are 2 of 4 well-established phenomena that demonstrate that extinction does not erase the conditioned stimulus (CS)-US association. However, reinstatement of extinguished eyeblink CRs has never been demonstrated, and spontaneous recovery of extinguished eyeblink CRs has not been systematically demonstrated in rodent eyeblink conditioning. In Experiment 1, US reexposure was administered 24 hr prior to a reinstatement test. In Experiment 2, US reexposure was administered 5 min prior to a reinstatement test. In Experiment 3, a long, discrete cue (a houselight), present in all phases of training and testing, served as a context within which each trial occurred to maximize context processing, which in other preparations has been shown to be required for reinstatement. In Experiment 4, an additional group was included that received footshock exposure, rather than US reexposure, between extinction and test, and contextual freezing was measured prior to test. Spontaneous recovery was robust in Experiments 3 and 4. In Experiment 4, context freezing was strong in a group given footshock exposure but not in a group given eye shock US reexposure. There was no reinstatement observed in any experiment. With stimulus conditions that produce eyeblink conditioning and research designs that produce reinstatement in other forms of classical conditioning, we observed spontaneous recovery but not reinstatement of extinguished eyeblink CRs. This suggests that reinstatement, but not spontaneous recovery, is a preparation- or substrate-dependent phenomenon.     

Medial dorsal thalamic lesions impair blocking and latent inhibition of the conditioned eyeblink response in rats

The effects of lesions of the medial dorsal thalamic nucleus (MD) on blocking and latent inhibition (LI) of the rat eyeblink response were examined in the present study. Previous work has demonstrated that the cingulate cortex and related thalamic areas are involved in processing conditioning stimuli throughout training. The experiments in the present study tested the hypothesis that disruption of cingulothalamic stimulus processing produced by lesions of the MD would impair 2 types of associative learning that involve decremental changes in attention. In Experiment 1, MD lesions severely impaired blocking. In Experiment 2, MD lesions severely impaired LI. The results indicate that lesions of the MD impair incremental, decremental, or both types of changes in stimulus processing during learning.     

Inhibition of the eyeblink reflex in the human infant

In human adults the eyeblink elicited by a given stimulus can be inhibited if that stimulus is preceded by another stimulus at an appropriate lead interval. In the present work, pairs of eyeblink-eliciting stimuli separated by 300-1200 msec were presented to sleeping preterm and full-term infants as well as to adults. Preterm infants did not exhibit reliable inhibition at any interval. Full-term infants did so, but they required longer interstimulus intervals than were needed for inhibition in the adult subjects. Results imply that the neural systems that mediate reflex inhibition are functional at birth, but that they are relatively slow to act.     

Ontogeny of eyeblink conditioned response timing in rats

Eyeblink conditioned response (CR) timing was assessed in adult and infant rats. In Experiment 1, adult rats were trained with a 150-ms tone conditioned stimulus (CS) paired with a periorbital shock unconditioned stimulus (US; presented at 200- or 500-ms interstimulus intervals [ISIs]). The rats acquired CRs with 2 distinct peaks that occurred just before the US onset times. Experiments 2 and 3 examined developmental changes in CR timing in pups trained on Postnatal Days 24-26 or 32-34. Experiment 3 used a delay conditioning procedure in which the tone CS continued throughout the ISIs. Pups of both ages exhibited robust conditioning. However, there were age-related increases in the percentage of double-peaked CRs and in CR timing precision. Ontogenetic changes in eyeblink CR timing may be related to developmental changes in cerebellar cortical or hippocampal function.     

Effect of brain-stem lesions on retention of a conditioned reflex in cats

The effects of central brain-stem lesions on memory was studied in eight animals with previously acquired avoidance motor conditioned reflexes. The prelesion training included conditioning to flashes or clicks, differentiation and transfer. After extensive bilateral, two-stage electrolytic lesions of the central mesencephalon and after subsequent recovery for 5–12 weeks, the animals were subjected to reconditioning, redifferentiation and retransfer. The lesions did not produce loss of the previously established conditioned response. The memory of training prior to the lesion was perfect and comparable to that in normal cats with equal intervals in the training.     

Tracking early and late stages of information processing: Contributions of startle eyeblink reflex modification

Startle eyeblink modification was examined as a measure of information processing. College students were presented with tones of 5 and 7 s duration of either high or low pitch, followed by startle-eliciting stimuli at lead intervals of 120, 2.000, 4,500, or 6,000ms. Attention to tones was manipulated by instructing the task group to count the longer tones of either pitch. The no-task group had no instructed task. Startle eyeblink was inhibited at the short lead interval and facilitated at the long lead intervals in both groups. The task group showed greater inhibition and facilitation during attended than during ignored tones, indicating that early and late controlled processing was occurring. In the task group, I he degree of facilitation appeared to reflect the degree of cognitive demands of the task. Startle eyeblink modification may provide a sensitive measure of the nature and timing of stapes of processing in active and passive attentional conditions.     

Long-term retention of the classically conditioned eyeblink response in rats

Retention of the classically conditioned eyeblink response in rats was tested with a conditioned stimulus (CS)-alone extinction test and 2 sessions of reacquisition training. Retention of the eyeblink conditioned response (CR) during both tests was highest 24 hr and 1 month after initial acquisition. Three months after initial acquisition, responding during the CS-alone test was at baseline, but there was significant savings during reacquisition. By 6 months after initial acquisition, the memory for the eyeblink CR was not expressed in either test. The group differences in retention, despite initial acquisition of the eyeblink CR to equal levels, suggest that rat eyeblink conditioning may provide a useful behavioral model for studying the neural processes underlying memory retention and loss.     

Cerebellar neuronal activity expresses the complex topography of conditioned eyeblink responses

Pavlovian eyeblink conditioning is a useful model system for studying how the temporal relationship between a conditioned stimulus and an unconditioned stimulus is represented in the brain. As an example, the response topography formed under a complex conditioning paradigm, involving 2 randomly alternating interstimulus intervals (ISIs), manifests a conditioned response (CR) with 2 distinctive peaks that correspond to the 2 ISIs. The authors present the first full report of neuronal activities in the cerebellar interpositus nucleus of rabbits performing bimodal responses. All CR-related activities exhibited firing patterns that highly correlated with and preceded eyeblink responses. The striking similarity between the time course of bimodal CRs and neuronal responses indicates that neuronal activities in the cerebellum are causally related to the production of behavioral CRs.     

Unilateral enhancement of early and late blink reflex components in hemidystonia

The side-to-side differences in the EMG activity of the early and late components of blink reflex, regarded as revealing the state of excitability of the brain stem reflex centers, have been analyzed in patients with unilateral dystonia without demonstrable brain lesions. It has been observed that both early and late responses of direct blink reflex were higher on the side affected by hemidystonia than on the contralateral one, while the latency values were in the normal range. Possibility that an abnormal output from the striatum towards the brainstem structures involved in blink reflex appears on the affected side of hemidystonic patients is discussed.     

Septal lesions facilitate the shift from conditioned escape to conditioned avoidance behavior in the rat.

Normal rats were given 1000 training trials in a discriminated lever-press avoidance task. Those animals which exhibited consistent escape behavior but minimal avoidance responding were subjected to either septal lesions or control operations. One week later they were retested in the avoidance apparatus for an additional 1000 trials. Rats with large septal lesions exhibited an immediate increase in avoidance performance relative to the control rats. This increase occurred without a concomitant increase in number of lever-press responses. The performance of 3 out of 4 rats with smaller more dorsal septal lesions was unaffected by the surgery.     

Extinction of conditioned eyeblink responses in patients with cerebellar disorders

Extinction of conditioned eyeblink responses (CRs) was analyzed in sixteen patients with pure cortical cerebellar degeneration, 14 patients with lesions within the territory of the superior cerebellar artery (SCA), 13 patients with infarctions within the territory of the posterior inferior cerebellar artery (PICA) and 45 age-matched controls. Three-dimensional (3D) magnetic resonance (MRI) data sets were acquired in patients with focal lesions to identify affected cerebellar lobules and possible involvement of nuclei. Eyeblink conditioning was performed using a standard delay protocol. At the end of the experiment 10 CS-alone trials were presented as extinction trials. Controls showed significant effects of extinction that is a significant decline comparing CR-incidences in the extinction trials and the last block of 10 trials of the paired trials. In the group of all cerebellar patients, however, no significant effects of extinction were observed. In patients with unilateral lesions effects of extinction were present on the unaffected, but not on the affected side. Deficits of extinction were observed in PICA and SCA patients both with and without involvement of cerebellar nuclei. Extending previous reports in cerebellar patients the present findings show that the ipsilateral cerebellar hemisphere contributes to extinction of conditioned eyeblink responses in humans. It cannot be ruled out, however, that impaired acquisition affected the extinction results.     

Conditioned facilitation of the unconditioned reflex after classical eyeblink conditioning.

The present study (N=40) investigated the time-course of conditioned facilitation of the unconditioned eyeblink reflex (UR). In a single-cue delay classical conditioning procedure, a tone conditioned stimulus (CS) signaled an airpuff unconditioned stimulus (airpuff US) to the eye. A paired group received 40 trials of CS/US presentations with an interstimulus interval (ISI) of 200 ms. An unpaired group received an equal number of explicitly unpaired presentations of the CS and US. Thereafter, eyeblink reflex facilitation was assessed by presenting 94 dB white noise (noise US) 10, 30, 50, 100, 150, and 1000 ms after CS onset. In the paired group, URs were significantly increased as early as 100 ms after CS onset compared to the unpaired group. This reflex facilitation was correlated with CR magnitude, indicating that conditioned facilitation of eyeblink URs indexes an early, automatic, preattentive stage in CR formation.     

Effects of bilateral lesions of the cerebellar interpositus nucleus on the conditioned forelimb flexion reflex in mice

Three groups of mice, unoperated controls, sham and lesioned, were submitted to an associative conditioning of forelimb flexion reflex (FFR). Light and tone constituted the conditioned stimulus (CS) paired with a forelimb electric shock, the unconditioned stimulus (UCS). The first two groups were able to acquire an appropriate conditioned response. In the third group, each animal received a bilateral lesion of the cerebellar interpositus nucleus (IN). The subjects of this group were unable to acquire the conditioning. When bilateral lesions of the IN were done after the acquisition, no effect of the lesions could be detected during retention test sessions 10 days after surgery, by comparison with sham controls. It is therefore concluded that the cerebellar interpositus nucleus is an essential part of the circuit for the acquisition of associative conditioning of the forelimb flexion response in mice, but not for the retention of this task. Moreover, no direct sensorimotor effect of the lesion on performance itself could be evoked.     

The conditioned reflex regulation of the blood pressure

Summary The conditioned reflexes formed on the basis of unconditioned changes of the blood pressure in stimulation of the proprioceptors with the aid of static load were studied in experiments on 3 dogs. It was demonstrated that the reflexes referred to above are rapidly, acquired, reestablished and changed, but in comparison with this their extinction is slower. It is thus assumed that these conditioned reflexes provide the adjustment of the function of the cardiovascular system to the constantly changing conditions of the body existence.Presented by Academician K. M. Bykov     

Neuronal correlates of conditioned inhibition of the eyeblink response in the anterior interpositus nucleus

Conditioned inhibition (CI) of the rat eyeblink response and the neuronal correlates of CI in the cerebellar interpositus nucleus were examined in the present study. In Experiment 1, CI was established with a novel, 3-group design. In Experiment 2, neuronal activity in the anterior interpositus nucleus was recorded during CI training and testing. Each rat was given 2 training phases and then tested for CI with summation and retardation tests. Rats given CI training showed behavioral inhibition compared with rats in 2 control groups. Neuronal activity in the anterior interpositus nucleus correlated with behavioral responding during discrimination training and during the summation test. The results suggest that neurons in the cerebellar anterior interpositus nucleus may participate in the acquisition or expression of CI.     

Cerebellar cortex and eyeblink conditioning: bilateral regulation of conditioned responses

We examined the role of the cerebellum in classical conditioning of the nictitating membrane response (NMR) of rabbits by comparing the effects of unilateral and bilateral cerebellar cortical lesions. Using extended preoperative conditioning to ensure high levels of learning, we confirmed that unilateral lesions of lobules HVI and ansiform lobe impaired conditioned responses (CRs) previously established to an auditory conditioned stimulus, but did not prevent some relearning with post-operative retraining. Bilateral lesions of HVI and ansiform lobe produced similar impairments of CRs, but also prevented subsequent relearning. Unilateral cortical lesions produced significant enhancement of unconditioned response (UR) amplitudes to periorbital electrical stimulation. Bilateral cortical lesions enhanced UR amplitudes to a lesser extent. Because there was no correlation between the degree of CR impairment and UR enhancement across the unilateral and bilateral lesion groups, the suggestion that the lesions impaired CRs due to general effects upon performance, rather than due to losses of learning, is not supported. Both sides of the cerebellar cortex contribute towards learning a unilaterally trained CR. This finding is important for the re-interpretation of unilateral, reversible inactivation studies that have found no involvement of the cerebellar deep nuclei in the acquisition of NMR conditioning. In addition, we found conditioning-dependent modifications of unconditioned responses that were particularly apparent at low intensities of periorbital electrical stimulation. This finding is important for the re-interpretation of studies that have found apparent changes in the UR of conditioned subjects after cerebellar lesions.     

Effect of medial septal lesions on conditioned taste aversion in the rat.

Rats that had sustained lesions of the medial septum developed a conditioned food aversion to sweetened condensed milk at the same rate as controls. This aversion was produced by post-ingestion administration of lithium chloride in ascending doses given on alternate days. Although development of the aversion was the same in lesioned animals as in controls, recovery from it was more rapid in the lesioned animals.     

Prepulse effects on the photic eyeblink reflex: Evidence for startle-dazzle theory

Weak visual prestimulation effects on the early (R50, 50–80 ms) and late (R80, 80–200 ms) components of the eyeblink response to bright light flashes were studied in 16 normal individuals. At a lead time of 120 ms, R50 was inhibited relative to no-prepulse control trials, whereas R80 was facilitated. According to the proposed startle-dazzle theory, luminance onset transients trigger an initial response, R50, that is functionally related to startle. Sustained stimulation then activates prolonged eyelid (R80) and pupil responses, which serve to minimize retinal bleaching. Although the sensitivity of the photic blink reflex to attention is controversial, R50 latency showed a pattern suggestive of inhibition of return (Posner & Cohen, 1984, Attention and performance, Vol. X, pp. 531–556, Hillsdale, NJ: Erlbaum). Analyses in a patient with unilateral occipital lobe damage supported previous evidence that inhibition by a visual prepulse requires neocortex, but facilitation does not.