Feedback control of Purkinje cell activity by the cerebello‐olivary pathway

Bengtsson, Fredrik; Svensson, Patrik; Hesslow, Germund

doi:10.1111/j.1460-9568.2004.03789.x

Cited by 57 publications

(49 citation statements)

References 35 publications

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“…This stimulation-independent and NBQX-induced suppression of IN firing rate is consistent with previous reports of the tonic effects of blocking IO input to the cerebellum (Benedetti et al, 1983;Bengtsson et al, 2004). It appears that NBQX downregulated the firing rate of the IO and this upregulated the activity of Purkinje cells in the cerebellar cortex (Batini et al, 1985;Lang, 2001;Bengtsson et al, 2004). The increased activity of these inhibitory cells then suppressed activity of IN neurons, as shown by our measurements.…”

Section: Involvement Of the Io In Expression Of Crs: Tonic Dysfunctiosupporting

confidence: 80%

Cerebellar Dysfunction Explains the Extinction-Like Abolition of Conditioned Eyeblinks After NBQX Injections in the Inferior Olive

Zbarska

Bloedel²,

Bracha³

2008

J. Neurosci.

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Classical conditioning of the eyeblink response is a form of motor learning that is controlled by the intermediate cerebellum and related brainstem structures. The inferior olive (IO) is commonly thought to provide the cerebellum with a "teaching" unconditioned stimulus (US) signal required for cerebellar learning. Testing this concept has been difficult because the IO, in addition to its putative learning function, also controls tonic activity in the cerebellum. Previously, it was reported that inactivation of AMPA/kainate receptors in the IO produces extinction of conditioned responses (CRs), suggesting that it blocks the transmission of US signals without perturbing the functional state of the cerebellum. However, the electrophysiological support for this critical finding was lacking, mostly because of methodological difficulties in maintaining stable recordings from the same set of single units throughout long drug injection sessions in awake rabbits. To address this critical issue, we used our microwire-based multiple single-unit recording method. The IO in trained rabbits was injected with the AMPA/kainate receptor blocker, 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide (NBQX), and its effects on CR expression and neuronal activity in the cerebellar interposed nuclei (IN) were examined. We found that NBQX abolished CR expression and that delayed drug effects were independent of the presentation of the conditioned stimulus and were therefore not related to extinction. In parallel to these behavioral effects, the spontaneous neuronal activity and CR-related neuronal responses in the IN were suppressed, suggesting cerebellar dysfunction. These findings indicate that testing the role of IO in learning requires methods that do not alter the functional state of the cerebellum.

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Section: Involvement Of the Io In Expression Of Crs: Tonic Dysfunctiosupporting

confidence: 80%

Cerebellar Dysfunction Explains the Extinction-Like Abolition of Conditioned Eyeblinks After NBQX Injections in the Inferior Olive

Zbarska

Bloedel²,

Bracha³

2008

J. Neurosci.

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“…The best described cerebellar feedback loop is the cerebello-olivary-cerebellar system that has been proposed to regulate cerebellar information processing during learning and also the tonic activity of Purkinje cells via negative feedback (Andersson et al, 1988;Bengtsson et al, 2004). Projections from the interposed nuclei to the inferior olive are inhibitory.…”

Section: Involvement Of the Bc In Cr Acquisitionmentioning

confidence: 99%

Inactivation of cerebellar output axons impairs acquisition of conditioned eyeblinks

2006

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Acquisition of classically conditioned eyeblink responses (CRs) in the rabbit critically depends on intermediate cerebellum-related neural circuits. A highly efficient method for determining possible sites of plasticity within eyeblink circuits is the reversible inactivation of circuit components during learning. Inactivation of either the HVI region of the cerebellar cortex or the cerebellar interposed nuclei (IN) during learning is known to prevent CR acquisition. In contrast, inactivating cerebellar efferent axons in the brachium conjunctivum (BC) with small injections of tetrodotoxin (TTX) has been reported to have no effect on CR acquisition. This suggested that the intermediate cerebellum is essential for learning CRs and that activity mediated by the BC is not required for this process. Since we previously found that BC inactivation blocks CR extinction we re-examined its role in CR acquisition. To ensure complete and long-lasting inactivation of the BC, we injected before each training session doses of TTX that were larger than those in the previous acquisition study. Contrary to the previous negative findings, we found that this temporary block of axons in the brachium conjunctivum prevented normal acquisition of CRs. Injecting TTX directly in the adjacent lateral lemniscus, which could possibly influence CR acquisition, had no effect on learning. In addition, a functional test of TTX diffusion around the BC indicated that the inactivation did not affect other known parts of eyeblink circuits, such as the cerebellar interposed nuclei, the middle cerebellar peduncle or the contralateral red nucleus. We conclude that this form of associative learning in the rabbit eyeblink system requires extra-cerebellar learning and/or cerebellar learning that depends on the operation of cerebellar feedback loops.

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“…A central tenet of the model is that the reinforcement value of a paired trial depends on the existing associative strength between the presented stimuli (3,4). Neural mechanisms for several phenomena related to the Rescorla-Wagner model have already been proposed (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16). In this paper, we present evidence from our eyeblink setup that builds on and advances prior thinking regarding the physiological basis of the RescorlaWagner model.…”

mentioning

confidence: 71%

“…However, disinhibiting the cerebellar nuclei also leads to inhibition of the inferior olive via the GABAergic nucleo-olivary pathway (6,7,16,38,39). This can be seen by recording field potentials on the cerebellar surface (40,41), or the frequency of spontaneous complex spikes in Purkinje cells, during conditioning (14).…”

Section: Discussionmentioning

confidence: 99%

“…This can be seen by recording field potentials on the cerebellar surface (40,41), or the frequency of spontaneous complex spikes in Purkinje cells, during conditioning (14). Because the inhibition is associated with an unusually long delay (42), it will coincide with the arrival of the US (13), which suggests that the nucleo-olivary pathway is part of a negative-feedback system that controls cerebellar learning (5,16).…”

Section: Discussionmentioning

confidence: 99%

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Purkinje cell activity during classical conditioning with different conditional stimuli explains central tenet of Rescorla–Wagner model

Rasmussen

Zucca

Johansson

et al. 2015

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

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A central tenet of Rescorla and Wagner’s model of associative learning is that the reinforcement value of a paired trial diminishes as the associative strength between the presented stimuli increases. Despite its fundamental importance to behavioral sciences, the neural mechanisms underlying the model have not been fully explored. Here, we present findings that, taken together, can explain why a stronger association leads to a reduced reinforcement value, within the context of eyeblink conditioning. Specifically, we show that learned pause responses in Purkinje cells, which trigger adaptively timed conditioned eyeblinks, suppress the unconditional stimulus (US) signal in a graded manner. Furthermore, by examining how Purkinje cells respond to two distinct conditional stimuli and to a compound stimulus, we provide evidence that could potentially help explain the somewhat counterintuitive overexpectation phenomenon, which was derived from the Rescorla–Wagner model.

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Feedback control of Purkinje cell activity by the cerebello‐olivary pathway

Cited by 57 publications

References 35 publications

Cerebellar Dysfunction Explains the Extinction-Like Abolition of Conditioned Eyeblinks After NBQX Injections in the Inferior Olive

Cerebellar Dysfunction Explains the Extinction-Like Abolition of Conditioned Eyeblinks After NBQX Injections in the Inferior Olive

Inactivation of cerebellar output axons impairs acquisition of conditioned eyeblinks

Purkinje cell activity during classical conditioning with different conditional stimuli explains central tenet of Rescorla–Wagner model

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