Rabbit Nictitating Membrane Response Research Articles

Differential conditioning of the rabbit's nictitating membrane response to serial compound stimuli.

Differential conditioning of the rabbit's nictitating membrane response to serial compound stimuli.

Hippocampal lesions disrupt classical conditioning of cross-modality reversal learning of the rabbit nictitating membrane response

The role of the hippocampus and subiculum in classical conditioning of tone-light discrimination reversal learning of the rabbit nictitating membrane response was investigated using aspiration lesions of both limbic structures. Only two of seven animals with hippocampal-subicular damage successfully reached reversal criteria within 21 days of conditioning, although all hippocampectomized animals learned the initial discrimination at rates equivalent to those of two control groups. Thus, previously reported deficits in two-tone reversal learning seen after similar lesions are not due to increased within-modality generalization to the conditioned stimuli (CS) serving as the CS + and CS −.

Concurrent development of excitatory and inhibitory associations during backward conditioning

After backward pairings with a paraorbital shock, a tone CS was an effective punisher of lick­ ing in rabbits, yet yielded retarded forward acquisition of the rabbit's nictitating membrane response. The observation of both excitatory and inhibitory associative effects after a common training protocol challenges the assumption of a unidimensional associative continuum and sup­ ports approaches that assert a multidimensional structure to associations. A continuing paradox for associative theories is the mul­ tiplicity of effects that result from following an aversive US with a CS. When the backward pairings are indirectly assessed with transfer-of-control paradigms, the CS usually suppresses an instrumental baseline (Burkhardt, 1980; Heth, 1976; Mowrer & Aiken, 1954; Williams, Dyck, & Tait, in press). This observation has led to the conclusion that backward conditioning produces excita­ tory associative effects. In contrast, when the effects of the backward pairings are assessed with a retardation-of­ learning test, in which the CS and US are paired in a for­ ward order and the development of CRs to the CS is moni­ tored, the rate of CR acquisition is usually retarded (Plot­ kin & Oakley, 1975; Siegel & Domjan, 1971). The re­ tarded acquisition has led to the conclusion that backward conditioning produces inhibitory associative effects (Hall, 1984). In attempts to resolve the paradoxical effects of back­ ward pairings, an association has usually been viewed as a unidimensional construct for which excitation and inhi­ bition are mutually exclusive outcomes. As an associa­ tion develops with backward pairings, a transient excita­ tory associative phase is thought to precede a terminal inhibitory association (Pavlov, 1932; Wagner & Terry, 1975). Consequently, research strategies have emphasized functional relationships between associative strength and dynamic variables such as time, number of conditioning trials, and US-CS interval. Accordingly, one assessment procedure is selected, and variables that might affect as­ sociative strength are manipulated (Heth, 1976; Maier, Rapaport, & Wheatley, 1976; Quesnel, Ten Have, & Tait, 1980; Siegel & Domjan, 1974). This strategy has produced reliable differences in the associative strength accrued to the backward CS, but not reliable evidence for

Summation and configuration in conditioning of the rabbit's nictitating membrane response to compound stimuli.

Summation and configuration in conditioning of the rabbit's nictitating membrane response to compound stimuli.

Invertebrate Learning and Memory: From Behavior to Molecules

Classical ethologists have provided a long and rich tradition of stud ying the learning and memory capabilities of a variety of invertebrate animals (Schneirla 1929, von Frisch 1950, Lindauer 1960). In recent years, however, interest in this field has been renewed because it has become clear that many invertebrate animals can provide powerful model systems in which to explore the cellular and molecular mechanisms of learning and memory. Thus, a variety of disciplines such as neuroethology, psychology, and modern neurobiology have merged in a concerted effort to develop invertebrate preparations in which these combined approaches can be focused on the general theme of the cellular basis of behavioral plasticity. This overall strategy has come to be known as a simple-systems approach to the study of learning and memory. A simple-systems approach is not the exclusive domain of invertebrate research. The general strategy of such an approach is to try to identify neural circuits involved in a particular form oflearning and then attempt to specify the precise locus and nature of the cellular changes that are involved. This approach has been successfully applied in a number of vertebrate systems. These include eyeblink conditioning in the cat (Kim et al 1983, Woody et a1 1983, Woody 1984), cardiac conditioning in the pigeon (Cohen 1980, 1984), and conditioning of the nictitating membrane response in rabbit (Thompson et a1 1983, 1984, Moore et a1 1982, Harvey et aI 1985), as well as cellular analog systems in cerebellum (Ito 1982), the red nucleus (Tskahara, 1984), and hippocampus (McNaughton et al 1 978, Levy &

Lesions of the retrosplenial cortex produce deficits in reversal learning of the rabbit nictitating membrane response: implications for potential interactions between hippocampal and cerebellar brain systems.

The effect of bilateral lesions of the retrosplenial cortex on discrimination reversal learning of the rabbit nictitating membrane response was examined. Results showed that animals with such lesions were not impaired in their ability to acquire a cross-modality discrimination, but were severely impaired in their ability to reverse the discrimination once it was learned. All animals failed at the reversal phase of the task because they displayed high levels of conditioned responding to both the CS+ and the CS-. Thus bilateral damage to the retrosplenial cortex results in deficits in reversal learning that are highly similar to those observed after bilateral hippocampectomy. These findings are interpreted within a conceptual framework that characterizes multisynaptic projections from the hippocampus to the retrosplenial cortex, and ultimately to the cerebellum, as responsible for the behavioral expression of learning-related changes in hippocampal pyramidal cell activity.

Summation and configuration in conditioning of the rabbit's nictitating membrane response to compound stimuli.

Summation and configuration in conditioning of the rabbit's nictitating membrane response to compound stimuli.

Lesions of the retrosplenial cortex produce deficits in reversal learning of the rabbit nictitating membrane response: Implications for potential interactions between hippocampal and cerebellar brain systems.

Lesions of the retrosplenial cortex produce deficits in reversal learning of the rabbit nictitating membrane response: Implications for potential interactions between hippocampal and cerebellar brain systems.

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

The effects of amphetamine injection, hippocampal lesions, and cortical lesions were examined during classical conditioning of the rabbit nictitating membrane response. An optimal interstimulus interval 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 animals, which received explicitly unpaired presentations of the conditioned stimulus and unconditioned stimulus, failed to exceed spontaneous response rates throughout training. The failure of hippocampectomy to accelerate conditioning under an optimal interstimulus interval (ISI) does not appear to be due to a "ceiling effect." Rather, it was 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.

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

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

Systemic elevation of ACTH and hippocampal activity during classical conditioning of the rabbit nictitating membrane response

Hippocampal multiple-unit activity was recorded from rabbits injected with ACTH or with vehicle alone during classical conditioning of the nictitating membrane response. Elevated systemic levels of the hormone had no apparent effect on behavioral learning or on the hippocampal “model” of the conditioned response. Data from a control group, which received unpaired presentations of the CS and US, showed that the hippocampal response is learning-dependent. These results indicated that the behavioral effects of ACTH in intact animals is not, as previously conjectured, mediated by a disruption of hippocampal function.

The CS-US interval (ISI) function in rabbit nictitating membrane response conditioning with very long intertriai intervals

In Experiment 1, four values of conditioned stimulus-unconditioned stimulus interval, or interstimulus interval (ISI) (200, 500, 800, and 1,100 msec) were studied in one trial/day acquisition of the conditioned nictitating membrane response of the rabbit. The 1,100-msec ISI group was superior to the other groups, contrary to the usual findings of ISI studies in the conditioning literature. In Experiment 2, effective conditioning levels were attained with an ISI as long as 2,200 msec, when the intertriai interval was set at either 24 or 48 h. Results are interpreted in terms of the role of orienting responses in the conditioning process.

Classical conditioning of the nictitating membrane response in aged rabbits.

There was no difference between old and young animals in acquisition of the conditioned response in the delay conditioning paradigm, nor were there any age-related differences in generalization to the tone CS or in sensitivity to the tone CS or eye shock UCS. In the trace conditioning paradigm, however, old animals acquired the conditioned response significantly slower than young animals. Because the same stimulus parameters and the same responses were used in both paradigms, it is unlikely that the age-related differences in trace conditioning were due to differences in stimulus sensitivity, motor deficits, motivation, or fatigue. Rather, the differences appear due to associative factors. The increased demands of the trace paradigm, which includes a within trial memory component, may be a critical factor in the age related disruption. Moreover, recent data suggest that trace and delay conditioning may involve different neuronal systems (e.g., hippocampus appears necessary for trace but not delay conditioning) and these systems may be differentially effected by the aging process.

Unit activity recorded from the globus pallidus during classical conditioning of the rabbit nictitating membrane response

Single and multiple unit activity were recorded from the region of the globus pallidus (GP) in rabbits during classical conditioning of the nictitating membrane response. The most common response recorded in the GP was a short latency (> 60 ms) change in firing following presentations of the pure tone conditioned stimulus (CS) and the corneal airpuff unconditioned stimulus (US). This response pattern was present in 39% of the pallidal records, and appeared to be elicited by the auditory components of the CS and US. Similar response patterns were seen in a few records from the putamen, entopeduncular nucleus, and ventral pallidum/substantia innominata. All of the single units that displayed this response pattern had a very sporadic pattern of spontaneous activity. Several other records from the GP displayed short latency responses after US presentations that appeared to be related to the tactile component of the airpuff. Responses of pallidal neurons to the CS and US were largely unaffected by the training procedures. It is concluded that this structure is most likely not directly involved in the classical conditioning of simple, striated muscle responses.

Relationship between heterosynaptic reflex facilitation and acquisition of the nictitating membrane response in control and scopolamine- injected rabbits

Classical conditioning of the rabbit nictitating membrane response was accomplished by presenting a 100-msec tone conditioned stimulus at intervals of 0, 100, 200, 400, and 800 msec before the presentation of a 100-msec shock unconditioned stimulus. In addition, tone-alone and shock-alone trials were interspersed during conditioning. On the first day of conditioning, during which there was no evidence of acquisition of conditioned responses to the tone conditioned stimulus, the amplitudes of the nictitating membrane response evoked on paired tone-shock trials were compared with the amplitudes obtained on shock-alone trials to provide a measure of reflex facilitation. There was a significant correlation (+0.86) in control animals between the degree of reflex facilitation and the degree of learning demonstrated at the various tone-shock intervals. Both reflex facilitation and learning were absent at the 0-msec tone-shock interval, increased at the 100-msec interval, reached a maximum at the 200-msec interval, and then declined at the longer intervals. Scopolamine (0.4 mg/kg) did not affect the amplitude of the nictitating membrane response elicited on shock-alone trials but eliminated any evidence of reflex facilitation or learning at the 100- and 800-msec intervals and significantly reduced both reflex facilitation and learning at the 200- and 400-msec intervals. The comparable effects of scopolamine on both reflex facilitation and learning were reflected by a significant correlation (+0.95) between these two measures.(ABSTRACT TRUNCATED AT 250 WORDS)

Neural and endocrine effects on classical conditioning: A comparison of ACTH and hippocampectomy

The effects of bilateral hippocampal lesions and systemic elevation of ACTH were compared using the classically conditioned rabbit nictitating membrane response. Animals with hippocampal lesions and unoperated animals that received ACTH (5 I.U./kg) exhibited a facilitated rate of acquisition and decreased conditioned response onset latency relative to normal control groups or animals with cortical lesions. The administration of ACTH did not alter performance in animals with hippocampal damage, indicating that the effects of these treatments are not additive. The performance of a second group of animals that was treated with a smaller dosage of ACTH (2.5 I.U./kg) was no different from that of any other group, suggesting a dose-dependent effect of the hormone. The selective replication of hippocampal deficits ascribed to a loss of response modulation suggests that ACTH may influence learning by stimulating hippocampal neurons.

Age-related disruption of trace but not delay classical conditioning of the rabbit's nictitating membrane response.

Young (6 months of age) and old (36-60 months) New Zealand albino rabbits underwent classical conditioning of the nictitating membrane response in either a delay conditioning (Experiment 1) or a trace conditioning (Experiment 2) paradigm. There was no difference between old and young animals in acquisition of the conditioned response in the delay paradigm, nor were there any age-related differences in generalization to the tone conditioned stimulus (CS) or in sensitivity to the tone CS or eye shock unconditioned stimulus. In the trace conditioning paradigm, however, old animals acquired the conditioned response significantly more slowly than young rabbits. Because the same stimulus parameters and the same response were used in both experiments, it is unlikely that age-related differences in trace conditioning were due to stimulus sensitivity, motivation, or fatigue. The results are discussed in terms of how brain changes that accompany aging could differentially affect these two types of classical conditioning.

Age-related disruption of trace but not delay classical conditioning of the rabbit's nictitating membrane response.

Age-related disruption of trace but not delay classical conditioning of the rabbit's nictitating membrane response.

Differential effects of hippocampectomy on classically conditioned rabbit nictitating membrane response related to interstimulus interval.

The effects of hippocampal ablation on acquisition rates and temporal characteristics of classically conditioned nictitating membrane responses were examined in groups of rabbits trained with a 150-, 300-, or 600-ms interstimulus interval. Acquisition rates were accelerated in the 150- and 600-ms groups. No effect was present in the 300-ms group. Response onset latencies were also affected in the 150-ms group. These findings were interpreted to support the notion that the hippocampus modulates learned motor behavior by a neural model of the response to be executed.

Differential effects of hippocampectomy on classically conditioned rabbit nictitating membrane response related to interstimulus interval.

Differential effects of hippocampectomy on classically conditioned rabbit nictitating membrane response related to interstimulus interval.