Acquisition, Extinction, and Reacquisition of a Cerebellar Cortical Memory Trace

Jirenhed, Dan-Anders; Bengtsson, Fredrik; Hesslow, Germund

doi:10.1523/jneurosci.4202-06.2007

Cited by 272 publications

(336 citation statements)

References 48 publications

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“…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). In the Purkinje cell circuit, long-term depression is induced at the parallel fiber-Purkinje cell synapses by the conjunctive stimulation of parallel fibers and climbing fibers and suppresses the tonic inhibition of Purkinje cells in the interpositus nucleus circuit.…”

Section: Discussionmentioning

confidence: 99%

“…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). According to this model, convergence of the CS and US signals induces long-term depression at the parallel fiber-Purkinje cell synapses.…”

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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Fig. 2a, the same trace was inadvertently used for the electrophysiological records of RNB (DOXuntreated) and RNB (DOX-withdrawn).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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“…The disinhibition of interpositus neurons causes an increase in cerebellar output and may promote induction of mossy fiber-interpositus long-term potentiation (Mauk and Donegan 1997;. Evidence for cerebellar cortical LTD during learning comes from studies that recorded Purkinje cell activity extracellularly during dEBC, showing pauses in simple spike activity when CRs occur (Hesslow and Ivarsson 1994;Green and Steinmetz 2005;Jirenhed et al 2007). Decreasing glutamate release at parallel fiber-Purkinje cell synapses with WIN55,212-2 may impair induction of LTD in vivo by attenuating postsynaptic depolarization that occurs when CS and US inputs co-occur.…”

Section: Discussionmentioning

confidence: 99%

Central cannabinoid receptors modulate acquisition of eyeblink conditioning

Steinmetz

Freeman²

2010

Learn. Mem.

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Delay eyeblink conditioning is established by paired presentations of a conditioned stimulus (CS) such as a tone or light, and an unconditioned stimulus (US) that elicits the blink reflex. Conditioned stimulus information is projected from the basilar pontine nuclei to the cerebellar interpositus nucleus and cortex. The cerebellar cortex, particularly the molecular layer, contains a high density of cannabinoid receptors (CB1R). The CB1Rs are located on the axon terminals of parallel fibers, stellate cells, and basket cells where they inhibit neurotransmitter release. The present study examined the effects of a CB1R agonist WIN55,212-2 and antagonist SR141716A on the acquisition of delay eyeblink conditioning in rats. Rats were given subcutaneous administration of 1, 2, or 3 mg/kg of WIN55,212-2 or 1, 3, or 5 mg/kg of SR141716A before each day of acquisition training (10 sessions). Dose-dependent impairments in acquisition were found for WIN55,212-2 and SR141716A, with no effects on spontaneous or nonassociative blinking. However, the magnitude of impairment was greater for WIN55,212-2 than SR141716A. Dose-dependent impairments in conditioned blink response (CR) amplitude and timing were found with WIN55,212-2 but not with SR141716A. The findings support the hypothesis that CB1Rs in the cerebellar cortex play an important role in plasticity mechanisms underlying eyeblink conditioning.

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“…In a variety of systems, CF activity has been shown to encode unexpected events and errors in movement, information appropriate for instructing circuit changes during motor learning (23)(24)(25)(26). Also consistent with a teaching role are the observations that direct electrical stimulation of IO/CFs can substitute for (27), that inhibition and lesion of the IO/CFs can prevent associative learning (28), and that lesions of the IO in trained animals result in extinction with continued paired training (29).…”

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confidence: 83%

Prolonging the postcomplex spike pause speeds eyeblink conditioning

Maiz

Karakossian

Pakaprot

et al. 2012

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

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Climbing fiber input to the cerebellum is believed to serve as a teaching signal during associative, cerebellum-dependent forms of motor learning. However, it is not understood how this neural pathway coordinates changes in cerebellar circuitry during learning. Here, we use pharmacological manipulations to prolong the postcomplex spike pause, a component of the climbing fiber signal in Purkinje neurons, and show that these manipulations enhance the rate of learning in classical eyelid conditioning. Our findings elucidate an unappreciated aspect of the climbing fiber teaching signal, and are consistent with a model in which convergent postcomplex spike pauses drive learning-related plasticity in the deep cerebellar nucleus. They also suggest a physiological mechanism that could modulate motor learning rates.associative learning | pavlovian | ZD 7288 | 1-EBIO | rebound

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Acquisition, Extinction, and Reacquisition of a Cerebellar Cortical Memory Trace

Cited by 272 publications

References 48 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

Central cannabinoid receptors modulate acquisition of eyeblink conditioning

Prolonging the postcomplex spike pause speeds eyeblink conditioning

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