Unconditioned Nictitating Membrane Research Articles

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 an unconditioned stimulus (US) in the absence of a conditioned stimulus (CS). Three experiments monitored rabbit nictitating (Oryctolagus cuniculus) membrane unconditioned responses to 5 intensities and 4 durations of periorbital electrical stimulation before and after CS or US manipulation. CRM occurred after 12 days of CS-US pairings but not following unpaired CS/US presentations or restraint. CRM survived CS-alone and CS/US-unpaired extinction of the conditioned response (CR) but not presentations of the US 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.

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

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

Effects of serotonin 5-HT(2A/2C) antagonists on associative learning in the rabbit.

The 5-HT(2A/2C) receptor antagonist, ritanserin, was reported to retard the acquisition of conditioned responses (CRs) during classical conditioning of the rabbit's nictitating membrane (NM) response. The present study compared the effects of ritanserin on acquisition of CRs to a tone conditioned stimulus (CS) with that of the 5-HT(2A/2C) receptor antagonist, LY-53,857 and the 5-HT2A selective antagonist, MDL-11,939. All three drugs were injected at equimolar doses of 0.067, 0.67 and 6.7 micromol/kg, SC, 1 h before behavioral testing. Ritanserin and MDL-11,939 retarded CR acquisition to a tone CS, while LY-53,857 had no effect. Control experiments demonstrated that ritanserin (1 micromol/kg), MDL-11,939 (1 micromol/kg) and LY-53,857 (2 micromol/kg) had no effect on baseline responding or non-associative responding to the CS. However, both ritanserin and MDL-11,939 impaired the performance of the unconditioned NM reflex, as measured by a decrease in UR amplitudes on US alone trials, while LY-53,857 had no effect. In previously trained animals, ritanserin robustly impaired the performance of CRs, as measured by a reduced ability of the CS to elicit CRs, while the effects of LY-53,857 and MDL-11,939 were marginal. The retardation of associative learning produced by ritanserin and MDL-11,939 may have been due, at least in part, to their impairment of the NM reflex arc. Since MDL-11,939 is a highly selective 5-HT2A antagonist, the retardation of learning and impairment of UR amplitudes produced by MDL-11,939 and ritanserin may have been due to blockade of the 5-HT2A receptor. The ability of ritanserin and MDL-11,939 to produce effects on learning and performance that were opposite to that of 5-HT(2A/2C) agonists suggests that they may be acting as inverse agonists at that receptor. These results stress the importance of the serotonergic system for optimal associative learning and motor function.

Projections from the thoracic cord to the cerebellar nuclei in the rat

Kinematic and dynamic analyses were employed to study the effects of cerebellar lesions on conditioned and unconditioned nictitating membrane responses in the rabbit. It was found that conditioned responses acquired to an auditory stimulus accelerated in two bursts as indicated by two distinct peaks of acceleration. The second peak of acceleration was very weak during the early portions of conditioning but became a prominent feature of the conditioned response over 16 sessions of conditioning. The second peak of acceleration in the conditioned response was more sensitive to cerebellar damage than was the first peak. When lesions of the cerebellum permanently reduced the amplitude of conditioned responses, but did not affect their frequency, the second peak of acceleration was nearly abolished while the first peak was unaffected. When cerebellar lesions profoundly impaired both the amplitude and frequency of conditioned responses, large and permanent impairments occurred in both peaks of acceleration. Lesions of the anterior interpositus nucleus most severely impaired both peaks of acceleration in the conditioned response and significantly reduced the acceleration of unconditioned responses across a wide range of intensities of corneal air puff. The deficit in the acceleration of unconditioned responses became manifest only after membrane extension exceeded 0.12 mm. The impairment in the amplitude of the unconditioned response after cerebellar lesions more closely approximated the impairment in the amplitude of the conditioned response when the force-generating properties of the conditioned and unconditioned stimuli were equated. It was hypothesized, therefore, that one reason why conditioned responses are so easily disrupted by cerebellar lesions is because they are of low force and not simply because they are learned.It was proposed that the two peaks of acceleration that characterize the conditioned response represent the function of two distinct anatomical systems. The first, a short-latency system, initiates the response and is most likely mediated by circuits that traverse the pontomedullary reticular formation. The second, a longer-latency system, amplifies response amplitude and its neural basis remains to be elucidated. The two components of the conditioned response may reflect two sequential bursts of activity in the accessory abducens nucleus, the principal site of the motoneurons for the retractor bulbi muscle, or may reflect the synergistic activity of the accessory abducens nucleus and the motor nuclei of the other extraocular muscles. It was concluded that the vulnerability of the second component of the conditioned response to cerebellar damage reflects an important role for the cerebellum in modulating the degree to which long-latency neural systems contribute to the ongoing performance of learned and unlearned behaviors.

1503 Projections from the thoracic cord to the cerebellar nuclei in the rat

Kinematic and dynamic analyses were employed to study the effects of cerebellar lesions on conditioned and unconditioned nictitating membrane responses in the rabbit. It was found that conditioned responses acquired to an auditory stimulus accelerated in two bursts as indicated by two distinct peaks of acceleration. The second peak of acceleration was very weak during the early portions of conditioning but became a prominent feature of the conditioned response over 16 sessions of conditioning. The second peak of acceleration in the conditioned response was more sensitive to cerebellar damage than was the first peak. When lesions of the cerebellum permanently reduced the amplitude of conditioned responses, but did not affect their frequency, the second peak of acceleration was nearly abolished while the first peak was unaffected. When cerebellar lesions profoundly impaired both the amplitude and frequency of conditioned responses, large and permanent impairments occurred in both peaks of acceleration. Lesions of the anterior interpositus nucleus most severely impaired both peaks of acceleration in the conditioned response and significantly reduced the acceleration of unconditioned responses across a wide range of intensities of corneal air puff. The deficit in the acceleration of unconditioned responses became manifest only after membrane extension exceeded 0.12 mm. The impairment in the amplitude of the unconditioned response after cerebellar lesions more closely approximated the impairment in the amplitude of the conditioned response when the force-generating properties of the conditioned and unconditioned stimuli were equated. It was hypothesized, therefore, that one reason why conditioned responses are so easily disrupted by cerebellar lesions is because they are of low force and not simply because they are learned.It was proposed that the two peaks of acceleration that characterize the conditioned response represent the function of two distinct anatomical systems. The first, a short-latency system, initiates the response and is most likely mediated by circuits that traverse the pontomedullary reticular formation. The second, a longer-latency system, amplifies response amplitude and its neural basis remains to be elucidated. The two components of the conditioned response may reflect two sequential bursts of activity in the accessory abducens nucleus, the principal site of the motoneurons for the retractor bulbi muscle, or may reflect the synergistic activity of the accessory abducens nucleus and the motor nuclei of the other extraocular muscles. It was concluded that the vulnerability of the second component of the conditioned response to cerebellar damage reflects an important role for the cerebellum in modulating the degree to which long-latency neural systems contribute to the ongoing performance of learned and unlearned behaviors.

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

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

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 second 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.

The temporary inactivation of the red nucleus affects performance of both conditioned and unconditioned nictitating membrane responses in the rabbit.

These experiments are part of a series of studies examining the role of the red nucleus in the performance of the conditioned and unconditioned nictitating membrane reflexes in the rabbit. Specifically, the experiments test the hypothesis that the temporary inactivation of the red nucleus selectively affects the performance of the conditioned reflex. The experiments were designed to assess the effects of lidocaine and control saline microinjections on conditioned as well as unconditioned responses in both paired and unpaired trials. Rabbits were chronically implanted with cannulae through which small injecting tubes were passed stereotaxically to the red nucleus. The animals were conditioned using a delay paradigm in which a 1 kHz tone and an air puff applied to the cornea were used as the unconditioned and conditioned stimulus, respectively. Once conditioned, the effects of either lidocaine or saline injection were evaluated while alternating paired trials with unpaired trials in which only the air puff was applied. The principal finding of this study was that the amplitudes of both the conditioned and unconditioned responses were reduced following lidocaine injection into the red nucleus. The effect on the unconditioned response amplitude could not be ascribed to any interaction between the conditioned and unconditioned responses, since it also was present in the unpaired trials. The reduction in amplitude of the conditioned and unconditioned responses was shown to be correlated with changes in other characteristics of the same responses. The data suggest that the red nucleus contributes to the performance of both the conditioned and unconditioned nictitating membrane reflexes and consequently is not likely to be involved only in pathways responsible for mediating and/or storing the engram for the conditioned reflex.

6-Hydroxydopamine induced impairment of Pavlovian conditioning in the rabbit.

This study employed bilateral, intraventricular injections of 6-hydroxydopamine (6-HDA) to examine the effects of monoamine depletion on Pavlovian conditioning of the rabbit's nictitating membrane response. 6-HDA produced dose-dependent and highly correlated decreases in the rate of acquisition of conditioned responses and in the telencephalic content of 5-HT, DA, and NE. At the highest dose of 6-HDA (1340 micrograms), 5-HT, DA, and NE were reduced by 42, 48, and 89%, respectively, and the number of trials required to achieve criterion acquisition was increased by 123%. Control experiments established that the highest dose of 6-HDA: 1) had no effect on the unconditioned nictitating membrane reflex; 2) had no effect on the threshold of the conditioned stimulus for eliciting conditioned responses; and 3) produced only a small, less than 5%, decrease in nonassociative responding. It was concluded that decreases in 5-HT, DA, and NE can impair associative learning without altering sensory or motor function.

Changes in the motor pattern of learned and unlearned responses following cerebellar lesions: A kinematic analysis of the nictitating membrane reflex

Kinematic and dynamic analyses were employed to study the effects of cerebellar lesions on conditioned and unconditioned nictitating membrane responses in the rabbit. It was found that conditioned responses acquired to an auditory stimulus accelerated in two bursts as indicated by two distinct peaks of acceleration. The second peak of acceleration was very weak during the early portions of conditioning but became a prominent feature of the conditioned response over 16 sessions of conditioning. The second peak of acceleration in the conditioned response was more sensitive to cerebellar damage than was the first peak. When lesions of the cerebellum permanently reduced the amplitude of conditioned responses, but did not affect their frequency, the second peak of acceleration was nearly abolished while the first peak was unaffected. When cerebellar lesions profoundly impaired both the amplitude and frequency of conditioned responses, large and permanent impairments occurred in both peaks of acceleration. Lesions of the anterior interpositus nucleus most severely impaired both peaks of acceleration in the conditioned response and significantly reduced the acceleration of unconditioned responses across a wide range of intensities of corneal air puff. The deficit in the acceleration of unconditioned responses became manifest only after membrane extension exceeded 0.12 mm. The impairment in the amplitude of the unconditioned response after cerebellar lesions more closely approximated the impairment in the amplitude of the conditioned response when the force-generating properties of the conditioned and unconditioned stimuli were equated. It was hypothesized, therefore, that one reason why conditioned responses are so easily disrupted by cerebellar lesions is because they are of low force and not simply because they are learned. It was proposed that the two peaks of acceleration that characterize the conditioned response represent the function of two distinct anatomical systems. The first, a short-latency system, initiates the response and is most likely mediated by circuits that traverse the pontomedullary reticular formation. The second, a longer-latency system, amplifies response amplitude and its neural basis remains to be elucidated. The two components of the conditioned response may reflect two sequential bursts of activity in the accessory abducens nucleus, the principal site of the motoneurons for the retractor bulbi muscle, or may reflect the synergistic activity of the accessory abducens nucleus and the motor nuclei of the other extraocular muscles. It was concluded that the vulnerability of the second component of the conditioned response to cerebellar damage reflects an important role for the cerebellum in modulating the degree to which long-latency neural systems contribute to the ongoing performance of learned and unlearned behaviors.

Effects of MDA upon differential serial compound conditioning and reflex modification of the rabbit's nictitating membrane response

The present investigations sought to determine the effects of 3,4-methylenedioxyamphetamine (MDA) on: 1) differential conditioning of the rabbit's nictitating membrane response to the serial compounds A-X-US (tone-light-reinforced compound) and B-X (white noise-light-unreinforced compound) by examining differential responding to A and B and their conditional control over responding to X within the compounds (Experiment 1); and 2) the ability of the compound stimuli and their components to modify the amplitude of the unconditioned nictitating membrane response (Experiment 2). Experiment 1 revealed that MDA decremented differential responding to the serial compounds and their A and B components, while enhancing conditioned responding to the X component. In addition, Experiment 2 indicated that MDA attenuated reflex modification to the compounds and their A and B components, but facilitated reflex modification to X alone. The results of these experiments indicated that MDA operated to alter the intensity, distinctiveness, and persistence (short-term memory) of stimulus representations.

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

The present study 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 rabbit. Before behavioral training, the central nucleus of the amygdala and adjacent areas were lesioned electrolytically. In the 1st experiment, the lesioned animals exhibited no reflex facilitation of the unconditioned NM response at conditioned stimulus (CS)-unconditioned stimulus (US) intervals of 125-8,000 ms. In the 2nd and 3rd experiments in which one CS-US 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 1000-Hz tone CS intensity was 65 dB but not when the intensity was 85 dB.

Electrical activity of the lateral rectus muscle and abducens nerve during unconditioned eye retraction induced by corneal stimulation in the cat

Horizontal eye movements, the electromyogram of the lateral rectus muscle and the evoked electroneurogram of the VIth nerve were recorded in the alert cat during air puff stimulation of the cornea. A burst of activity was observed in the lateral rectus muscle following air puff stimulation of the ipsilateral or contralateral eye. This activity produced rotational eye movement. The VIth nerve produced two volleys of activity that were interpreted as the R1 and R2 parts of the reflex. It can be concluded that the lateral rectus muscle participates in the ocular retraction following trigeminal stimulation. It is further suggested that motoneurons in the main abducens nucleus participate in the corneal reflex, permitting several final pathways for conditioned and unconditioned nictitating membrane extension.

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 rabbit. 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 5-12 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.

Reflex facilitation of the rabbit nictitating membrane response by an auditory stimulus as a function of interstimulus interval.

The ability of an auditory stimulus to facilitate the amplitude and latency of the unconditioned nictitating membrane (NM) response in rabbits was investigated over a wide range of interstimulus intervals (ISIs) for both delay (Experiments 1-4) and trace (Experiments 3 and 4) procedures. The auditory stimulus was a 1000-Hz tone (T) at either 85 or 95 dB, and the reflex-eliciting stimulus was a 2.0 psi (pounds per square inch) corneal air puff (AP). The results indicate that (a) robust facilitation of the NM response, as measured by an increased amplitude and a reduced latency, can be obtained at long ISIs (2,000-32,000 ms); (b) increasing the tone intensity can increase reflex facilitation of the peak amplitude; (c) at comparable ISIs, delay procedures produce more facilitation of both amplitude and latency than do trace procedures; and (d) when trace procedures are used, amplitude and latency facilitation by a 125-ms tone follows an inverted U-shaped ISI function in which facilitation peaks between 125 and 500 ms, rapidly decreases between 1,000 and 2,000 ms, and disappears by 4,000 ms.

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

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

Reflex facilitation of the nictitating membrane response remains after cerebellar lesions.

Reflex facilitation and associated properties were investigated during classical conditioning of the nictitating membrane (NM) response in rabbit. In the first experiment, the role of the cerebellum was examined by comparing the unconditioned responses of animals with bilateral lesions of the deep cerebellar nuclei with those of operated controls during counterbalanced tone/light (T/L) discrimination training. Both T and L facilitated unconditioned NM responses when used as the CS+ (conditioned stimulus), but neither facilitated when used as the CS-. There were no significant differences in the amount of reflex facilitation exhibited by animals with lesions compared with control animals. Animals with lesions, however, failed to acquire conditioned responses after 10 days of training, whereas all control animals met acquisition criterion within 4 days. In the second experiment, reflex facilitation was shown to decrement in a stimulus-specific manner when nonreinforced presentations of an auditory stimulus were given. The discussion of results focuses on the relation between reflex facilitation and classical conditioning in terms of behavioral properties and underlying neural systems.

Effects of morphine and LSD on the classically conditioned nictitating membrane response

Two experiments were carried out to determine the effects of LSD and morphine on the unconditioned nictitating membrane response of the rabbit elicited by 5 intensities of a 100 msec puff of air directed at the cornea, and on the acquisition of conditioned responses to a tone and light conditioned stimulus using the air-puff as an unconditioned stimulus. In Experiment 1, LSD tartrate (0.013 mg/kg) had no effect of the frequency, amplitude, magnitude or latency of the unconditioned response. However, LSD significantly enhanced the rate of acquisition of conditioned responses to both tone and light conditioned stimuli. In Experiment 2, morphine sulfate (5 mg/kg) had no effect on the frequency, amplitude, magnitude or latency of the unconditioned response, but significantly retarded the acquisition of conditioned responses to both tone and light conditioned stimuli. The results indicated that the enhancement of acquisition produced by LSD and the retardation of acquisition produced by morphine were not due to effects of the drugs on either the sensory processing of the air-puff unconditioned stimulus or on the motoric expression of the unconditioned response.

A brain stem region essential for the classically conditioned but not unconditioned nictitating membrane response

Radio-frequency lesions of the right dorsolateral pons severely impaired both acquisition and retention of the ipsilateral conditioned nictitating membrane response to both visual and auditory conditioned stimuli. Unconditioned responses were unaffected, and conditioning of the contralateral (left) eye was not impaired. These data suggest a critical role of the dorsolateral pons in the generation of conditioned responding in this preparation.

Amplitude of the rabbit’s unconditioned nictitating membrane response in the presence of a conditioned inhibitor

Using a light or backshock as the reinforced CS (A) and a tone or backshock as the conditioned inhibitor (X), rabbits experienced conditioned inhibition training in an A+/AX− paradigm. Following training, the amplitude of the unconditioned nictitating membrane response elicited by a mild (.5-mA) paraorbital shock was measured in the presence of X and AX and expressed as a percentage of the amplitude of the UR to the shock presented alone. In Experiment 1, the effect of X and AX on UR amplitude for conditioned inhibition animals was compared with that of control animals treated to a variety of pretest procedures. In general, UR amplitude in the presence of X exceeded that observed to the US presented alone. There was no consistent difference between the experimental and control groups. In Experiments 2–5, A test trials were added as an alternative reference point. Again, UR amplitude increased rather than decreased UR amplitude. In addition, X as a conditioned inhibitor enhanced the facilitating effect of A on UR amplitude in four out of five experiments. These findings have implications for theories of the “locus of action” of conditioned inhibitors.