The multiple roles of Purkinje cells in sensori-motor calibration: to predict, teach and command

Medina, Javier F.

doi:10.1016/j.conb.2011.05.025

Cited by 81 publications

(73 citation statements)

References 60 publications

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“…We observed a predilection of virus for the cerebellum with a cellular tropism for cerebellar Purkinje cells. These cells play an important role in cerebellar function and are key elements in motor learning and motor coordination (32). As human cases of TBE, we consistently found TBEV antigens in Purkinje cells, thereby confirming similarities of the viral tropism in the present TBE model and human TBE (28).…”

Section: Discussionsupporting

confidence: 80%

A Tick-Borne Encephalitis Model in Infant Rats Infected With Langat Virus

Maffioli

Grandgirard

Engler

et al. 2014

J Neuropathol Exp Neurol

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Tick-borne encephalitis virus (TBEV) is the causative agent of human TBE, a severe infection that can cause long-lasting neurologic sequelae. Langat virus (LGTV), which is closely related to TBEV, has a low virulence for human hosts and has been used as a live vaccine against TBEV. Tick-borne encephalitis by natural infection of LGTV in humans has not been described, but one of 18,500 LGTV vaccinees developed encephalitis. The pathogenetic mechanisms of TBEV are poorly understood and, currently, no effective therapy is available. We developed an infant rat model of TBE using LGTV as infective agent. Infant Wistar rats were inoculated intracisternally with 10 focus-forming units of LGTV and assessed for clinical disease and neuropathologic findings at Days 2, 4, 7, and 9 after infection. Infection with LGTV led to gait disturbance, hypokinesia, and reduced weight gain or weight loss. Cerebrospinal fluid concentrations of RANTES, interferon-γ, interferon-β, interleukin-6, and monocyte chemotactic protein-1 were increased in infected animals. The brains of animals with LGTV encephalitis exhibited characteristic perivascular inflammatory cuffs and glial nodules; immunohistochemistry documented the presence of LGTV in the thalamus, hippocampus, midbrain, frontal pole, and cerebellum. Thus, LGTV meningoencephalitis in infant rats mimics important clinical and histopathologic features of human TBE. This new model provides a tool to investigate disease mechanisms and to evaluate new therapeutic strategies against encephalitogenic flaviviruses.

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Section: Discussionsupporting

confidence: 80%

A Tick-Borne Encephalitis Model in Infant Rats Infected With Langat Virus

Maffioli

Grandgirard

Engler

et al. 2014

J Neuropathol Exp Neurol

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“…Transiently suppressing the spontaneous firing of these lateral PCs may have more subtle effects than reported here because their activity is thought to provide information about the current motor state but does not seem to contribute to the motor command directly (Miall et al, 2007). Indeed, recent work suggests that PC activity could play multiple roles in addition to directly controlling motor output (Medina, 2011), including providing a prediction of future movement kinematics (Pasalar et al, 2006) and serving as a teaching signal for downstream cells in the DCN (Pugh and Raman, 2006;Otis et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Precise Control of Movement Kinematics by Optogenetic Inhibition of Purkinje Cell Activity

et al. 2014

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Purkinje cells (PCs) of the cerebellar cortex are necessary for controlling movement with precision, but a mechanistic explanation of how the activity of these inhibitory neurons regulates motor output is still lacking. We used an optogenetic approach in awake mice to show for the first time that transiently suppressing spontaneous activity in a population of PCs is sufficient to cause discrete movements that can be systematically modulated in size, speed, and timing depending on how much and how long PC firing is suppressed. We further demonstrate that this fine control of movement kinematics is mediated by a graded disinhibition of target neurons in the deep cerebellar nuclei. Our results prove a long-standing model of cerebellar function and provide the first demonstration that suppression of inhibitory signals can act as a powerful mechanism for the precise control of behavior.

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“…Although there are various ways in which this information could be signaled, the results of experiment 3 point to a potential role for the cerebellum. Computationally elegant models have been developed in which the cerebellum contributes to motor learning by using sensory prediction errors to adapt the sensorimotor system (7,8,14). More recently, the cerebellum has been shown to have extensive anatomical and functional connections with subcortical and cortical regions-specifically, regions strongly associated with decision-making and reinforcement learning, including the ventral tegmental area, striatum, and prefrontal cortex (15)(16)(17)(18)(19)(20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

Credit assignment in movement-dependent reinforcement learning

McDougle

Boggess

Crossley

et al. 2016

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

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When a person fails to obtain an expected reward from an object in the environment, they face a credit assignment problem: Did the absence of reward reflect an extrinsic property of the environment or an intrinsic error in motor execution? To explore this problem, we modified a popular decision-making task used in studies of reinforcement learning, the two-armed bandit task. We compared a version in which choices were indicated by key presses, the standard response in such tasks, to a version in which the choices were indicated by reaching movements, which affords execution failures. In the key press condition, participants exhibited a strong risk aversion bias; strikingly, this bias reversed in the reaching condition. This result can be explained by a reinforcement model wherein movement errors influence decision-making, either by gating reward prediction errors or by modifying an implicit representation of motor competence. Two further experiments support the gating hypothesis. First, we used a condition in which we provided visual cues indicative of movement errors but informed the participants that trial outcomes were independent of their actual movements. The main result was replicated, indicating that the gating process is independent of participants' explicit sense of control. Second, individuals with cerebellar degeneration failed to modulate their behavior between the key press and reach conditions, providing converging evidence of an implicit influence of movement error signals on reinforcement learning. These results provide a mechanistically tractable solution to the credit assignment problem.decision-making | reinforcement learning | sensory prediction error | reward prediction error | cerebellum W hen a diner reaches across the table and knocks over her coffee, the absence of anticipated reward should be attributed to a failure of coordination rather than diminish her love of coffee. Although this attribution is intuitive, current models of decision-making lack a mechanistic explanation for this seemingly simple computation. We set out to ask if, and how, selection processes in decision-making incorporate information specific to action execution and thus solve the credit assignment problem that arises when an expected reward is not obtained because of a failure in motor execution.Humans are highly capable of tracking the value of stimuli, varying their behavior on the basis of reinforcement history (1, 2), and exhibiting sensitivity to intrinsic motor noise when reward outcomes depend on movement accuracy (3-5). In real-world behavior, the underlying cause of unrewarded events is often ambiguous: A lost point in tennis could occur because the player made a poor choice about where to hit the ball or failed to properly execute the stroke. However, in laboratory studies of reinforcement learning, the underlying cause of unrewarded events is typically unambiguous, either solely dependent on properties of the stimulus or on motor noise. Thus, it remains unclear how people assign credit to either extrins...

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The multiple roles of Purkinje cells in sensori-motor calibration: to predict, teach and command

Cited by 81 publications

References 60 publications

A Tick-Borne Encephalitis Model in Infant Rats Infected With Langat Virus

A Tick-Borne Encephalitis Model in Infant Rats Infected With Langat Virus

Precise Control of Movement Kinematics by Optogenetic Inhibition of Purkinje Cell Activity

Credit assignment in movement-dependent reinforcement learning

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