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

Heiney, Shane A.; Kim, Jinsook; Augustine, George J; Medina, Javier F.

doi:10.1523/jneurosci.4547-13.2014

Cited by 237 publications

(275 citation statements)

References 69 publications

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“…After 2 days of recovery, mice were trained in our custom-built head mount. The head mount was attached to metal posts that fix a foam running wheel below the animal (Chettih et al 2011;Heiney et al 2014). We trained the mice with practice runs in order for them to acclimate to moving while being head fixed above the wheel.…”

Section: Methodsmentioning

confidence: 99%

In vivo analysis of Purkinje cell firing properties during postnatal mouse development

Arancillo

White

Lin

et al. 2015

Journal of Neurophysiology

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Arancillo M, White JJ, Lin T, Stay TL, Sillitoe RV. In vivo analysis of Purkinje cell firing properties during postnatal mouse development. J Neurophysiol 113: 578 -591, 2015. First published October 29, 2014 doi:10.1152/jn.00586.2014.-Purkinje cell activity is essential for controlling motor behavior. During motor behavior Purkinje cells fire two types of action potentials: simple spikes that are generated intrinsically and complex spikes that are induced by climbing fiber inputs. Although the functions of these spikes are becoming clear, how they are established is still poorly understood. Here, we used in vivo electrophysiology approaches conducted in anesthetized and awake mice to record Purkinje cell activity starting from the second postnatal week of development through to adulthood. We found that the rate of complex spike firing increases sharply at 3 wk of age whereas the rate of simple spike firing gradually increases until 4 wk of age. We also found that compared with adult, the pattern of simple spike firing during development is more irregular as the cells tend to fire in bursts that are interrupted by long pauses. The regularity in simple spike firing only reached maturity at 4 wk of age. In contrast, the adult complex spike pattern was already evident by the second week of life, remaining consistent across all ages. Analyses of Purkinje cells in alert behaving mice suggested that the adult patterns are attained more than a week after the completion of key morphogenetic processes such as migration, lamination, and foliation. Purkinje cell activity is therefore dynamically sculpted throughout postnatal development, traversing several critical events that are required for circuit formation. Overall, we show that simple spike and complex spike firing develop with unique developmental trajectories.

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Section: Methodsmentioning

confidence: 99%

In vivo analysis of Purkinje cell firing properties during postnatal mouse development

Arancillo

White

Lin

et al. 2015

Journal of Neurophysiology

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“…The subject learns to emit a conditional blink response (CR) that is timed so that the maximum amplitude is reached close to the time of US onset. Eyeblink conditioning depends on the cerebellar cortex (4-6) and the overt CRs are driven by learned pause responses in the spontaneously active cerebellar Purkinje cells (7)(8)(9). These cells receive the CS signal via the mossy fiber/parallel fiber system, and the US signal via the climbing fibers from the inferior olive (10,11).…”

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confidence: 99%

Learned response sequences in cerebellar Purkinje cells

Jirenhed

Rasmussen

Johansson

et al. 2017

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

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Associative learning in the cerebellum has previously focused on single movements. In eyeblink conditioning, for instance, a subject learns to blink at the right time in response to a conditional stimulus (CS), such as a tone that is repeatedly followed by an unconditional corneal stimulus (US). During conditioning, the CS and US are transmitted by mossy/parallel fibers and climbing fibers to cerebellar Purkinje cells that acquire a precisely timed pause response that drives the overt blink response. The timing of this conditional Purkinje cell response is determined by the CS-US interval and is independent of temporal patterns in the input signal. In addition to single movements, the cerebellum is also believed to be important for learning complex motor programs that require multiple precisely timed muscle contractions, such as, for example, playing the piano. In the present work, we studied Purkinje cells in decerebrate ferrets that were conditioned using electrical stimulation of mossy fiber and climbing fiber afferents as CS and US, while alternating between short and long interstimulus intervals. We found that Purkinje cells can learn double pause responses, separated by an intermediate excitation, where each pause corresponds to one interstimulus interval. The results show that individual cells can not only learn to time a single response but that they also learn an accurately timed sequential response pattern.cerebellum | Purkinje cells | learning | timing | classical conditioning P laying the piano, typing on your keyboard, and uttering a sentence are all typical examples of complex behaviors. Although they involve simple movements as building blocks, they need to be executed with great temporal precision and in a specific sequential order. Utter phonemes in the wrong order or with incorrect timing, and the result is incomprehensible.

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“…2 In this learning paradigm, cerebellar Purkinje cells that control the blink learn to respond with a timed pause [3][4][5] in their tonic inhibition of cerebellar nuclear cells, leading to an excitatory signal that generates the overt blink. [6][7][8] The conditional and unconditional blink-eliciting signals reach the Purkinje cell via the mossy-parallel fiber system and climbing fibers respectively. 9 The Timing Mechanism is Intrinsic to the Purkinje Cell Virtually all neural timing models postulate that neurons learn to time their responses by altering the strength of synaptic connections for selected subpopulations of pre-synaptic neurons.…”

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confidence: 99%