Harmaline-induced impairment of Pavlovian conditioning in the rabbit

Harvey, J A; Romano, Anthony G.

doi:10.1523/jneurosci.13-04-01616.1993

Cited by 22 publications

(14 citation statements)

References 38 publications

(41 reference statements)

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“…The present results do not confirm the reported anti-learning effects of harmaline on classically conditioned nictitating membrane responses in rabbits (Harvey and Romano, 1993). An important difference is that conditioned blinks responses in cats are mainly mediated by the orbicularis oculi muscle/facial motor system, while in rabbits are mediated by the retractor bulbi/accessory abducens motor system (Trigo et al, 1999b;Gruart et aL, 2000).…”

Section: Discussioncontrasting

confidence: 99%

“…In the cat, the maximum frequency of harmalineinduced tremor at appropriate dose is 8-12Hz, which is the maximal rate of firing for inferior olive neurons (Llin~s and Volkind, 1973). Previous studies have concluded that harmaline disrupts learning (for example, the acquisition of classically conditioned nictitating responses), but not its performance, since it does not prevent the expression of an already-learned response (Tfirker and Miles, 1984;Harvey and Romano, 1993).…”

Section: Introductionmentioning

confidence: 99%

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Harmaline induces different motor effects on facial vs. skeletal-motor systems in alert cats

et al. 2001

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Harmaline's effects on reflex and classically conditioned eyelid responses and on tremor picked up by a coil attached to the back were measured in alert cats. Harmaline at a dose of 10 mg/kg produced skeletal muscle tremogenic effects that lasted 4h. Back movements presented a tremor-like displacement with a frequency peak at 10 Hz, but lid responses oscillated as in controls, at 20 Hz during both reflex and conditioned eyelid movements, with no increase in oscillation amplitude or frequency. The learning curves of harmaline-injected animals remained as in controls, but eyelid conditioned responses showed longer latencies, and smaller amplitude and peak velocity. Reflex and already-learned eyelid responses were not modified by harmaline. These results imply that neuronal control systems for skeletal-motor and facial responses are differentially affected by harmaline.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Harmaline induces different motor effects on facial vs. skeletal-motor systems in alert cats

et al. 2001

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“…Because both cerebellar areas contain IGF-I receptors (29,30) (35,36). An alternative hypothesis is that IGF-I, through climbing fiber collaterals (31), reaches the deep cerebellar nuclei and participates in plasticity-related events such as the proposed long-term potentiation of the synapse between mossy fiber afferents conveying the CS to the deep nuclei postsynaptic neuron (21)(22)(23)(24)34); this possibility remains to be explored. In addition, it has been shown that morphological changes occur in the cerebellar cortex during learning of the conditioned eyeblink response (37), and similar changes have been described as the consequence of trophic factors flowing through climbing fibers into the cerebellar cortex (20,38 Also, none ofthe antisense oligonucleotides used showed any noticeable effect upon cellular metabolic activity as indicated by measuring glutamate and -y-aminobutyric acid levels in the cerebellum and inferior olive.…”

Section: Resultsmentioning

confidence: 99%

Learning of the conditioned eye-blink response is impaired by an antisense insulin-like growth factor I oligonucleotide.

Castro‐Alamancos

Torres‐Alemán

1994

Proc. Natl. Acad. Sci. U.S.A.

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The cerebellum is thought to be critically involved in learning and retention of several types of classically conditioned motor responses. We investigated whether insulinlike growth factor I (IGF-I) may constitute an intercellular mediator of a motor lering task because previous findings indicated that IGF-I from the inferior olive modulates gluta- We used intraolivary infusions of an antisense oligonucleotide against insulin-like growth factor I (IGF-I) to selectively and reversibly deplete the cerebellum of IGF-I of inferior olive origin. Antisense oligonucleotides are widely used to block protein expression by interfering with mRNA translation (1). This is a recently available methodology that has not yet been extensively used to evaluate the role of specific proteins, localized in discrete brain regions, in learning and memory processes. Nevertheless, recent studies with transgenic mice have shown the great potential of specifically blocking a given gene in the study of learning and memory processes (2-4). However, the results obtained by using heterologous recombination techniques to block a given gene in the whole animal are difficult to interpret due to widespread actions of the mutation together with probable interference with developmental processes.The rationale underlying the use of an antisense oligonucleotide to study the involvement of specific proteins expressed in specific nuclei is as follows. Animals are injected with the antisense oligonucleotide in the nuclei projecting to the target area of the protein. This injection depletes the nucleus and its target area of the specific protein, against which the antisense has been designed. By measuring the levels ofthe protein in the target area and in the infused nuclei one can monitor the levels of the protein and correlate the effects of the antisense oligonucleotide with the behavioral performance of the animals. If learning and/or retention occurs in the absence ofthe protein, then this specific protein is not involved in the learning and/or retention process. However, if learning and/or retention does not occur during depletion ofthe protein, then the protein is critically involved in the learning and/or retention process.As a first step in the appropriate use of an antisense oligonucleotide, one must first identify the brain circuitry essentially involved in a given form of learning and memory. This has been achieved for the classical conditioning of discrete behavioral responses (5), where the cerebellum has been extensively shown to be critically involved. Climbing fibers originating in the inferior olive and parallel fibers from the granule cell layer of the cerebellum are the major input system to the Purkinje neuron in the cerebellar cortex (6). Together with the deep cerebellar nuclei, this basic circuitry is likely involved in learning of the classically conditioned eye-blink response (5, 6). It has been shown that mossy fibers originating in the pontine nuclei convey information to the cerebellum about the conditioned stimulus (C...

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“…75,76 This has been interpreted to reflect abnormal olivocerebellar interaction under harmaline treatment. It is presently under investigation if patients with essential tremor also have impairments of cerebellar function.…”

Section: Harmaline Tremor and Tremor In Humansmentioning

confidence: 99%