Cerebellar lesions and the nictitating membrane reflex: performance deficits of the conditioned and unconditioned response

Welsh, John P.; Harvey, J.

doi:10.1523/jneurosci.09-01-00299.1989

Cited by 291 publications

(182 citation statements)

References 39 publications

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“…Accumulated evidence has indicated that both Purkinje cells and interpositus nucleus circuits play a critical role in the execution and proper timing of CRs in associative eyeblink motor learning (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). The CS and US signals are conveyed to both the Purkinje cell and the interpositus nucleus circuits, and the convergent information of these two signals is capable of inducing neural plasticity at both circuits (2,26,36,37).…”

Section: Discussionmentioning

confidence: 99%

“…1a). The localization and underlying mechanisms of eyeblink conditioning have been extensively studied by different approaches including gene targeting (6)(7)(8)(9)(10)(11), lesioning (12)(13)(14)(15), mutant analysis (16), and pharmacological inactivation analyses (17)(18)(19)(20)(21)(22)(23). On the basis of these studies, one model proposes an essential role of the cerebellar Purkinje cell circuit in memory traces (24)(25)(26).…”

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confidence: 99%

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Conditioned eyeblink learning is formed and stored without cerebellar granule cell transmission

Wada

Kishimoto

Watanabe

et al. 2007

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

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), the authors note that in Fig. 2a, the same trace was inadvertently used for the electrophysiological records of RNB (DOXuntreated) and RNB (DOX-withdrawn). This error does not affect the conclusions of the article. The corrected figure and its legend appear below. (e and f ) Mean Ϯ SEM of firing rates of simple spikes (e) and complex spikes ( f) are shown with columns and bars, respectively. *** , P Ͻ 0.001 (comparison between DOX-treated RNB mice and all five other animals by the Scheffé test). (g) The extracellular recording site (red) was confirmed at the Purkinje cell layer by fluorescent Nissl staining. ML, molecular layer; PL, Purkinje cell layer; GL, granule cell layer. eyeblink conditioning ͉ interpositus nucleus ͉ Purkinje cell ͉ reversible neurotransmission blockade ͉ synaptic plasticity C lassical conditioning of the eyeblink reflex is elicited by paired presentation of conditioned stimulus (CS) with reinforcing unconditioned stimulus (US) (1-4). This associative motor learning is a basic form of cerebellum-dependent leaning. In eyeblink conditioning, the CS pathway includes the pontine nucleus and mossy fibers, whereas the US pathway includes the inferior olive and the climbing fibers (1-5). The mossy fibers project directly to the interpositus nucleus and indirectly to the cerebellar cortex via granule cells (1-5). The CS and US signals are thus conveyed to both the cerebellar cortex and the interpositus nucleus (Fig. 1a). The localization and underlying mechanisms of eyeblink conditioning have been extensively studied by different approaches including gene targeting (6-11), lesioning (12-15), mutant analysis (16), and pharmacological inactivation analyses (17-23). On the basis of these studies, one model proposes an essential role of the cerebellar Purkinje cell circuit in memory traces (24)(25)(26). According to this model, convergence of the CS and US signals induces long-term depression at the parallel fiber-Purkinje cell synapses. Because Purkinje cells are inhibitory, long-term depression causes a disinhibition of the interpositus nucleus and an increased input in the downstream motor pathways. The other model proposes that the memory trace is located in the interpositus nucleus and that conditioned responses (CRs) are properly evoked in response to CS by a timing signal from Purkinje cells (1,3,27,28). Eyeblink conditioning involves multiple learning processes, at least acquisition, expression, and storage of motor learning. Once the expression process of memory traces is impaired, it becomes difficult to define the key neural circuits responsible for expression, formation, and storage of memory traces.In this investigation, we adopted a novel reversible neurotransmission blocking (RNB) technique to explore the role of Purkinje cells and the interpositus nucleus in associative eyeblink conditioning. In the RNB transgenic mice, the tetanus toxin light chain is restrictedly expressed in granule cells under the control of a tetracycline-controlled reverse transactivator (rtTA) (29). Tetanus t...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Conditioned eyeblink learning is formed and stored without cerebellar granule cell transmission

Wada

Kishimoto

Watanabe

et al. 2007

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

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“…3C) to assess whether the modulation of CR expression was correlated with the animal's ability to perform the behavior (49). Because of considerable variations of the URs across the animals, all URs were normalized to average baseline responses before muscimol infusions.…”

Section: Effects Of Sequential Applications Of An Agonist and An Antamentioning

confidence: 99%

Cerebellar cortical inhibition and classical eyeblink conditioning

Bao

Chen

Kim

et al. 2002

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

124

110

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The cerebellum is considered a brain structure in which memories for learned motor responses (e.g., conditioned eyeblink responses) are stored. Within the cerebellum, however, the relative importance of the cortex and the deep nuclei in motor learning͞memory is not entirely clear. In this study, we show that the cerebellar cortex exerts both basal and stimulus-activated inhibition to the deep nuclei. Sequential application of a ␥-aminobutyric acid type A receptor (GABAAR) agonist and a noncompetitive GABAAR antagonist allows selective blockade of stimulus-activated inhibition. By using the same sequential agonist and antagonist methods in behaving animals, we demonstrate that the conditioned response (CR) expression and timing are completely dissociable and involve different inhibitory inputs; although the basal inhibition modulates CR expression, the conditioned stimulus-activated inhibition is required for the proper timing of the CR. In addition, complete blockade of cerebellar deep nuclear GABAARs prevents CR acquisition. Together, these results suggest that different aspects of the memories for eyeblink CRs are encoded in the cerebellar cortex and the cerebellar deep nuclei.learning ͉ memory ͉ cerebellar deep nuclei ͉ cerebellar cortex ͉ ␥-aminobutyric acid B ecause of the highly organized cytoarchitecture of its numerous neurons, the cerebellum has long been considered as a neuronal substrate for some forms of learning and memory (1-4). Accumulating evidence supports this view by demonstrating the critical roles of the cerebellum in motor learning (5-10). On the basis of empirical results and theoretical models, the basic neural circuitries underlying motor learning, such as classical conditioning and vestibulo-ocular-reflex adaptation, have been delineated (6,8,9). For example, in classical eyeblink conditioning, mossy fibers (mf) and climbing fibers (cf) are thought to convey conditioned stimulus (CS) and unconditioned stimulus (US) signals, respectively, to both the cerebellar cortex and the deep nuclei. Various types of synaptic plasticity have been demonstrated in these regions, including parallel fiberPurkinje cell long-term depression (pf-PC LTD) (11, 12) and long-term potentiation (pf-PC LTP) (13), pf-PC ␥-aminobutyric acid (GABA)-transmitting rebound potentiation (14), PC-deep nuclear neuron (DNN) LTD (15, 16), and LTP of extracellular responses in the cerebellar deep nuclei (17). These different types of plasticity may be involved in supporting learning in both the cerebellar cortex and deep nuclei (10,18,19).Although the early theoretical models only concerned the cerebellar cortex, recent studies implicated both the cortex and the deep nuclei in motor learning. Discrete lesions of the cerebellar interpositus nucleus (electrolytically, chemically, reversibly) consistently and completely prevent the acquisition and permanently and completely abolished retention͞expression of classically conditioned eyeblink responses in rabbits, rats, and mice (20-28). Cortical lesions affect various aspects of l...

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“…Via the red nucleus, and possibly other structures, the interpositus nucleus modulates orbicularis oculi motoneuron activity (Bracha and Bloedel, 1996;Gruart et al, 1997). Inactivation of the red (Chapman et al, 1990;Bracha et al, 1993) or the interpositus nuclei (Welsh and Harvey, 1989;Hesslow, 1994) reduces the trigeminal reflex blink amplitude. Conversely, interpositus and red nucleus stimulations excite facial motoneurons (Fanardjian and Manvelyan, 1984;Ivarsson and Hesslow, 1993).…”

Section: Neural Mechanisms Underlying the Two Adaptive Processesmentioning

confidence: 99%

Lid Restraint Evokes Two Types of Motor Adaptation

Schicatano

Mantzouranis²,

Peshori³

et al. 2002

J. Neurosci.

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Unilateral reduction in eyelid motility produced two modes of blink adaptation in humans. The first adaptive modification affected both eyelids. Stimulation of the supraorbital branch of the trigeminal nerve (SO) ipsilateral to the upper eyelid with reduced motility evoked bilateral, hyperexcitable reflex blinks, whereas contralateral SO stimulation elicited normally excitable blinks bilaterally. The probability of blink oscillations evoked by stimulation of the ipsilateral SO also increased with a reduction in lid motility. The increased probability of blink oscillations correlated with the enhanced trigeminal reflex blink excitability. Thus, the trigeminal complex ipsilateral to the restrained eyelid coordinated an increase in excitability and blink oscillations independent of the eyelid experiencing reduced motility. The second type of modification appeared only in the eyelid experiencing reduced motility. When tested immediately after removing lid restraint, blink amplitude increased in this eyelid relative to the normal eyelid regardless of the stimulated SO. A patient with seventh nerve palsy exhibited the same two patterns of blink adaptation. These results were consistent with two forms of adaptation, presumably because unilateral lid restraint produced two error signals. The corneal irritation caused by reduced blink amplitude generated abnormal corneal inputs. The difference between proprioceptive feedback from the blink and expected blink magnitude signaled an error in blink amplitude. The corneal irritation appeared to drive an adaptive process organized through the trigeminal complex, whereas the proprioceptive error signal drove an adaptive process involving just the motoneurons controlling the restrained eyelid.

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Cerebellar lesions and the nictitating membrane reflex: performance deficits of the conditioned and unconditioned response

Cited by 291 publications

References 39 publications

Conditioned eyeblink learning is formed and stored without cerebellar granule cell transmission

Conditioned eyeblink learning is formed and stored without cerebellar granule cell transmission

Cerebellar cortical inhibition and classical eyeblink conditioning

Lid Restraint Evokes Two Types of Motor Adaptation

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