fMRI of the Conscious Rabbit during Unilateral Classical Eyeblink Conditioning Reveals Bilateral Cerebellar Activation

Miller, Michael J.; Chen, Nan‐kuei; Liu, Limin; Tom, Brian C.; Weiss, Craig; Disterhoft, John F.; Wyrwicz, Alice M.

doi:10.1523/jneurosci.23-37-11753.2003

Cited by 64 publications

(62 citation statements)

References 39 publications

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“…Furthermore, inactivation of the right cerebellum on session 11 failed to change the incidence and peak amplitude of the established left CRs of the R-MSC guinea pigs, indicating that the right cerebellum was not essential for either the acquisition of left CRs at the later stage of training or the performance of well-established left CRs. These results implied a changing involvement of the right cerebellum in the left CR acquisition across behavioral training in albino guinea pigs, which fits well with evidence obtained from functional imaging studies in rabbits [11] and molecular biological studies in mice [12] . In the fMRI study of rabbits, significant learningrelated increases of the blood oxygenation level-dependent (BOLD) response were observed early in training within the bilateral cerebellar cortex and DCN.…”

Section: Role Of the Contralateral Cerebellum In The Acquisition Of Usupporting

confidence: 87%

“…According to the learning theories of Albus and Marr [34,35] , it seemed reasonable that plasticity could be generated in the unilateral cerebellum contralateral to the stimulated side of the US during the unilateral EBCC. Up to now, there some data have indirectly suggested the existence of this contralateral plasticity [10][11][12][13][14][15] . Moreover, there are anatomical pathways through which the unilateral cerebellum could control bilateral eyeblink responses.…”

Section: Role Of the Contralateral Cerebellum In The Acquisition Of Umentioning

confidence: 93%

“…It had been reported that lesions made in the unilateral cerebellum of rabbits abolished ipsilateral CRs, whereas learning was facilitated when training was switched to the contralateral eye [10] . Results from a recent functional imaging study of rabbits revealed activation in both the ipsilateral and the contralateral cerebellum during the acquisition of unilateral EBCC [11] . Moreover, increased expression of learning-related genes was observed in both sides of the cerebellum in mice [12] , which further supports the notion that some degree of plasticity occurs in the cerebellum contralateral to the applied side of the US.…”

Section: Introductionmentioning

confidence: 96%

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Involvement of the ipsilateral and contralateral cerebellum in the acquisition of unilateral classical eyeblink conditioning in guinea pigs

Lin

Huang

et al. 2009

Acta Pharmacol Sin

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Aim:The aim of this study was to evaluate the relative contributions of the ipsilateral and contralateral cerebellum to the acquisition of unilateral classical eyeblink conditioning (EBCC). Methods: The unilateral EBCC was achieved using a binaural tone conditioned stimulus (CS) paired with a left airpuff unconditioned stimulus (US). A high-resolution potentiometer was used to monitor eyeblink responses. Guinea pigs received one CS-US session followed by three CS-US sessions (sessions 2 to 4), during which microinjections of muscimol, a GABA A receptor agonist, were performed to reversibly inactivate the cerebellum unilaterally prior to training. To test whether any learning had occurred during these inactivation sessions, training was continued for six more CS-US sessions (sessions 5 to 10) without any inactivation. Results: Animals with inactivation of the left cerebellum had no signs of left conditioned response (CR) during sessions 2 to 4, and their CR acquisition during sessions 5 to 10 was not distinguishable from that of control animals during sessions 2 to 7. In contrast, animals with inactivation of the right cerebellum acquired left CRs during sessions 2 to 4, although their CR acquisition was significantly retarded during session 2. In addition, microinjections of muscimol into the right cerebellum did not affect left neuro-behavioral activity. Finally, microinjections of muscimol into either the left or the right cerebellum did not affect the performance of tone-airpuff evoked unconditioned response (UR). Conclusion: In contrast to the essential role of the ipsilateral cerebellum, the contralateral cerebellum is potentially involved in the acquisition of unilateral EBCC during the early stage of training.

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Section: Role Of the Contralateral Cerebellum In The Acquisition Of Usupporting

confidence: 87%

Section: Role Of the Contralateral Cerebellum In The Acquisition Of Umentioning

confidence: 93%

Section: Introductionmentioning

confidence: 96%

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Involvement of the ipsilateral and contralateral cerebellum in the acquisition of unilateral classical eyeblink conditioning in guinea pigs

Lin

Huang

et al. 2009

Acta Pharmacol Sin

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“…This hypothesis has been examined repeatedly with lesions (3-7) and inactivation of the AIN (8,9), and in mutant mice with Purkinje cell degeneration (10). Recent observations made using electron microscopy (11) or functional magnetic resonance imaging (12) further support the notion that the basic memory trace is formed in the AIN. On the other hand, the cerebellar cortex is implicated as a site of storage for the memory trace of CR timing (13).…”

mentioning

confidence: 95%

Molecular evidence for two-stage learning and partial laterality in eyeblink conditioning of mice

Park¹,

Onodera²,

Nishimura³

et al. 2006

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

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The anterior interpositus nucleus (AIN) is the proposed site of memory formation of eyeblink conditioning. A large part of the underlying molecular events, however, remain unknown. To elucidate the molecular mechanisms, we examined transcriptional changes in the AIN of mice trained with delay eyeblink conditioning using microarray, quantitative real-time RT-PCR, and in situ hybridization techniques. Microarray analyses suggested that transcriptionally up-regulated gene sets were largely different between early (3-d training) and late (7-d) stages. Quantitative real-time RT-PCR aided by laser microdissection indicated that the expression of representative EARLY genes (Sgk, IkBa, and Plekhf1) peaked at 1-d training in both the paired and unpaired conditioning groups, and was maintained at a higher level in the paired group than in the unpaired group after 3-d training. In situ hybridization revealed increased expression of these genes in broad cerebellar areas, including the AIN, with no hemispheric preferences. In contrast, the expression of representative LATE genes (Vamp1, Camk2d, and Prkcd) was selectively increased in the AIN of the 7-d paired group, with dominance in the ipsilateral AIN. Increased Vamp1 mRNA expression was restricted to the ipsilateral dorsolateral hump, a subregion of the AIN. These expression patterns of two distinct subsets of genes fit well with the twostage learning theory, which proposes emotional and motor learning phases, and support the notion that AIN has a crucial role in memory formation of eyeblink conditioning.gene expression ͉ interpositus nucleus C lassical eyeblink conditioning is conserved among various species. Although the neuronal circuitries are well defined and the cerebellum is considered to be the site of memory formation of the classically conditioned response (CR, i.e., eyeblink) (1), evidence is still conflicting regarding the neural substrate for the memory trace of eyeblink conditioning in the cerebellum.In contrast to the suggestion that the basic memory trace of the CR is formed in the cerebellar cortex (2), accumulating evidence suggests that the anterior interpositus nucleus (AIN) in the deep cerebellar nuclei (DCN) is the site of memory for the association between the conditioned stimulus (CS) and the unconditioned stimulus (US) formed in eyeblink conditioning. This hypothesis has been examined repeatedly with lesions (3-7) and inactivation of the AIN (8, 9), and in mutant mice with Purkinje cell degeneration (10). Recent observations made using electron microscopy (11) or functional magnetic resonance imaging (12) further support the notion that the basic memory trace is formed in the AIN. On the other hand, the cerebellar cortex is implicated as a site of storage for the memory trace of CR timing (13).Although the existence of a Purkinje cell-specific promoter like L7/pcp-2 made it possible to test the relevance of some molecules to cortical function in eyeblink conditioning in vivo (14,15), mechanistic studies at the molecular level of the AIN, which is ...

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“…However, no imaging study has explicitly compared the functional activation during trace and delay EBC in a conscious animal model. Previously, we demonstrated reliable detection of functional activation in the visual system of the awake, behaving rabbit using fMRI (Wyrwicz et al, 2000) and imaged learning-related changes in the rabbit cerebellum during delay EBC (Miller et al, 2003). This study uses fMRI in parallel with delay and trace EBC to investigate learning-related changes in the rabbit primary visual cortex (V1).…”

Section: Introductionmentioning

confidence: 99%

Functional Magnetic Resonance Imaging of Delay and Trace Eyeblink Conditioning in the Primary Visual Cortex of the Rabbit

Miller

Weiss²,

Song

et al. 2008

J. Neurosci.

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The primary sensory cortices have been shown in recent years to undergo experience-and learning-related plasticity under a variety of experimental circumstances. In this study, we used functional magnetic resonance imaging (fMRI) in parallel with both delay and trace eyeblink conditioning to image the learning-related functional activation within the primary visual cortex (V1) of awake, behaving rabbits. We expected that the differing level of forebrain dependence between these two conditioning paradigms should produce a differential blood oxygenation level-dependent (BOLD) functional response in V1. Our results showed a significant expansion of activated volume within V1, particularly early in learning, after training with the more cognitively demanding trace paradigm. In contrast, the simpler delay paradigm produced an increase in the magnitude of the BOLD response in activated voxels, but no significant change in activated volume. No accompanying learning-related changes were observed in the primary somatosensory cortex, which mediates the unconditioned stimulus. These results suggest that the recruitment of additional neurons within V1 is necessary to support the more demanding memory imposed by the trace interval. To our knowledge, this work is the first functional imaging study to compare directly trace and delay eyeblink conditioning in an animal model.

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fMRI of the Conscious Rabbit during Unilateral Classical Eyeblink Conditioning Reveals Bilateral Cerebellar Activation

Cited by 64 publications

References 39 publications

Involvement of the ipsilateral and contralateral cerebellum in the acquisition of unilateral classical eyeblink conditioning in guinea pigs

Involvement of the ipsilateral and contralateral cerebellum in the acquisition of unilateral classical eyeblink conditioning in guinea pigs

Molecular evidence for two-stage learning and partial laterality in eyeblink conditioning of mice

Functional Magnetic Resonance Imaging of Delay and Trace Eyeblink Conditioning in the Primary Visual Cortex of the Rabbit

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