Learned Movements Elicited by Direct Stimulation of Cerebellar Mossy Fiber Afferents

Hesslow, Germund; Svensson, Patrik; Ivarsson, Magnus

doi:10.1016/s0896-6273(00)80831-4

Cited by 106 publications

(106 citation statements)

References 31 publications

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“…Consistent with previous studies, mossy fiber stimulation supported robust learning (Fig. 5, top) (n ϭ 4; F (4,12) ϭ 18.2; p Ͻ 0.001) (Steinmetz et al, 1989;Hesslow et al, 1999). In an initial test session to confirm proper cannula placement, we infused muscimol to silence the AIN.…”

Section: Experiments 2: the Site Of Plasticity Underlying Slrs Is Upstsupporting

confidence: 85%

“…5). Therefore, both SLRs and normal conditioned responses are learned during red nucleus inactivation (Krupa et al, 1993) and with mossy fiber stimulation as the CS (Steinmetz et al, 1989;Hesslow et al, 1999). [It is unlikely that plasticity in a pathway downstream of the AIN that initially bypasses the red nucleus (e.g., via thalamus, cortex, and back to red nucleus) or presynaptic plasticity (e.g., increased transmitter release) in the red nucleus mediates SLRs, because the threshold for evoking eyelid closure by stimulating the AIN does not change with training (Tracy et al, 1998).]…”

Section: Experiments 5: Slrs Are Learned and Associativementioning

confidence: 99%

“…One such instance is eyelid conditioning, in which repeatedly presenting a tone conditioned stimulus (CS) together with mild electrical stimulation around the eye [the unconditioned stimulus (US)] promotes learning of a well-timed closure of the eyelid in response to the CS. The CS and US are conveyed to the cerebellum, respectively, by mossy and climbing fiber afferents (Mauk et al, 1986;Steinmetz et al, 1989;Hesslow et al, 1999), and the learned eyelid closure is driven by activity in the anterior interpositus nucleus (AIN) of the cerebellum (McCormick and Thompson, 1984;Choi and Moore, 2003) (see Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

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Learning-Induced Plasticity in Deep Cerebellar Nucleus

Ohyama¹,

Nores²,

Medina³

et al. 2006

J. Neurosci.

141

131

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Evidence that cerebellar learning involves more than one site of plasticity comes from, in part, pavlovian eyelid conditioning, where disconnecting the cerebellar cortex abolishes one component of learning, response timing, but spares the expression of abnormally timed short-latency responses (SLRs). Here, we provide evidence that SLRs unmasked by cerebellar cortex lesions are mediated by an associative form of learning-induced plasticity in the anterior interpositus nucleus (AIN) of the cerebellum. We used pharmacological inactivation and/or electrical microstimulation of various sites afferent and efferent to the AIN to systematically eliminate alternative candidate sites of plasticity upstream or downstream from this structure. Collectively, the results suggest that cerebellar learning is mediated in part by plasticity in target nuclei downstream of the cerebellar cortex. These data demonstrate an instance in which an aspect of associative learning, SLRs, can be used as an index of plasticity at a specific site in the brain.

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Section: Experiments 2: the Site Of Plasticity Underlying Slrs Is Upstsupporting

confidence: 85%

Section: Experiments 5: Slrs Are Learned and Associativementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Learning-Induced Plasticity in Deep Cerebellar Nucleus

Ohyama¹,

Nores²,

Medina³

et al. 2006

J. Neurosci.

141

131

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“…However, this observation is contradicted by recent studies, which have revealed short-latency responses after lesion or reversible disconnection of the cerebellar cortex and thus suggest that lesions that completely abolish conditioned responses may have involved inadvertent damage to the interpositus nucleus (Perrett et al, 1993;Perrett and Mauk, 1995;Garcia and Mauk, 1998;Garcia et al, 1999). Cerebellar nucleus plasticity mediated by the mossy fiber input has also been disputed on the basis that strong mossy fiber stimulation fails to elicit short-latency responses (Hesslow et al, 1999). It remains possible, however, that background Purkinje cell activity was able to suppress short-latency responses in this experiment and that evidence for short-latency responses would have been observed had the mossy fibers been stimulated during disconnection of the cerebellar cortex.…”

Section: Discussionmentioning

confidence: 93%

“…Arguments have been presented suggesting that a second site of plasticity outside the cerebellar cortex is not necessary for the expression of conditioned responses or at least that plasticity does not occur in the cerebellar nucleus (Yeo et al, 1985;Hesslow et al, 1999). Cerebellar nucleus plasticity is disputed by observations that lesions of the cerebellar cortex can abolish the expression of previously learned responses (Yeo et al, 1985).…”

Section: Discussionmentioning

confidence: 99%

A Mechanism for Savings in the Cerebellum

2001

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The phenomenon of savings (the ability to relearn faster than the first time) is a familiar property of many learning systems. The utility of savings makes its underlying mechanisms of special interest. We used a combination of computer simulations and reversible lesions to investigate mechanisms of savings that operate in the cerebellum during eyelid conditioning, a well characterized form of motor learning. The results suggest that a site of plasticity outside the cerebellar cortex (possibly in the cerebellar nucleus) can be protected from the full consequences of extinction and that the residual plasticity that remains can later contribute to the savings seen during relearning.Key words: plasticity; learning; memory; eyelid conditioning; simulation; LTD; LTP; extinction Riding a bicycle, playing the piano, and typing are examples of motor skills that illustrate our capacity for relearning that is much more rapid than the original learning. In the laboratory, this rapid relearning is known as savings and has been frequently studied in the context of Pavlovian conditioning of motor responses. During conditioning of eyelid responses for example, paired presentations of a tone [the conditioned stimulus (CS)] and a reinforcing unconditioned stimulus (US), such as periorbital electrical stimulation, promote the acquisition of a conditioned motor response (closing the eyelid in response to the tone). These conditioned responses can be unlearned during extinction training in which the CS is not paired with the US (Schneiderman et al., 1962). During reacquisition training, savings is apparent because relearning occurs much faster than original learning (Frey and Ross, 1968;Napier et al., 1992). The existence of savings is among the evidence supporting the notion that extinction training leaves behind residual excitatory strength (Reberg, 1972;Schactman et al., 1985;Kehoe, 1988). Here we present evidence for this residual-plasticity hypothesis in eyelid conditioning and characterize basic mechanisms involved in the savings observed with this form of motor learning.A variety of evidence indicates that the cerebellum is a necessary component of the neural pathways that mediate eyelid conditioning (Thompson, 1986;Thompson and Krupa, 1994;Raymond et al., 1996;Kim and Thompson, 1997). This evidence, combined with the well characterized synaptic organization and physiology of the cerebellum (Eccles et al., 1967;Llinas, 1981;Ito, 1984;Voogd and Glickstein, 1998), makes it possible to build large-scale computer simulations of the cerebellum and to test their capacity to display eyelid conditioning. We have shown previously that, by incorporating the evidence for plasticity at two sites (one in the cerebellar cortex and one in the cerebellar interpositus nucleus), these simulations can emulate the acquisition and extinction of conditioned responses (Medina et al., 2000). Here we report that these same simulations also display savings, even after extensive extinction training. In the simulations, the rules for plasticity combine...

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Time course of cerebellar morphological development in postnatal ferrets: Ontogenetic and comparative perspectives

Christensson

Broman

Garwicz

2007

J of Comparative Neurology

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We provide the first systematic description of the morphological ontogenesis of the ferret cerebellum and compare its relative time-course to that of the rat cerebellum. Overall cerebellar size, foliation, and thickness of cortical layers were quantified and Purkinje cell morphology was characterized at 24 timepoints in ferrets from postnatal day (P)1 to P63. The ferret cerebellum was substantially larger than that of the rat and had a much longer developmental period. In ferrets, Purkinje cells were dispersed into a monolayer by P9, the formation of folia declined abruptly around P20, and the external granular layer peaked in thickness around P22 and disappeared by P56. Timepoints of corresponding relative developmental maturity of the quantified architectural features of rat and ferret cerebella were determined and their relationship was analyzed by linear regression. The time-conversion equation derived, describing the relationship between cerebellar morphogenesis in the two species, had a determination coefficient (r2) of 0.95. Conspicuously, the equation predicted with high accuracy the timing of structural changes in individual Purkinje cells in the ferret cerebellum. The conversion equation should be useful for precise quantitative translation of data between studies of ferret and rat cerebellum and for comparisons between development of motor and sensory structures and functions in ferrets. The degree of similarity in the time-courses of cerebellar development in two distantly related mammals makes explicit in quantitative terms how remarkably conserved the cerebellum is in phylogenesis. Therefore, the methodology should be applicable to precise quantitative conversions of cerebellar developmental time-courses also between other species.

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Learned Movements Elicited by Direct Stimulation of Cerebellar Mossy Fiber Afferents

Cited by 106 publications

References 31 publications

Learning-Induced Plasticity in Deep Cerebellar Nucleus

Learning-Induced Plasticity in Deep Cerebellar Nucleus

A Mechanism for Savings in the Cerebellum

Time course of cerebellar morphological development in postnatal ferrets: Ontogenetic and comparative perspectives

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