Influence of data sampling methods on the representation of neural spiking activity in vivo

Heijden, Meike E van der; Brown, Amanda M.; Sillitoe, Roy V.

doi:10.1016/j.isci.2022.105429

Cited by 8 publications

(9 citation statements)

References 111 publications

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Section: Methodsmentioning

confidence: 99%

“…We previously showed that recording duration influences the estimation of neural firing parameters (79). Therefore, all parameter estimates in this paper are based on 30 seconds (s)-long recordings.…”

Section: Spike Sorting and Analysesmentioning

confidence: 99%

“…We previously found that the recording duration used for parameter analyses influences the presentation of spike properties. Therefore, we only included recordings with a duration of exactly 30 s and calculated parameter estimates as described above (79). Our previous study also showed that cerebellar nuclei neurons recorded in the same mouse had equal parameter variability as nuclei neurons recorded in different mice.…”

Section: Supervised Classifier Learnermentioning

confidence: 99%

“…Our previous study also showed that cerebellar nuclei neurons recorded in the same mouse had equal parameter variability as nuclei neurons recorded in different mice. Therefore, we treated all single nuclei neuron recordings as independent datapoints (79). We used the built-in supervised machine learning, MATLAB Classification Learner APP (The Mathworks Inc, version R2021a) to define spike signature parameter value cutoffs.…”

Section: Supervised Classifier Learnermentioning

confidence: 99%

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Cerebellar nuclei cells produce distinct pathogenic spike signatures in mouse models of ataxia, dystonia, and tremor

Heijden

Brown

Kizek

et al. 2023

Preprint

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The cerebellum contributes to a diverse array of motor conditions including ataxia, dystonia, and tremor. The neural substrates that encode this diversity are unclear. Here, we tested whether the neural spike activity of cerebellar output neurons predicts the phenotypic presentation of cerebellar pathophysiology. Using in vivo recordings as input data, we trained a supervised classifier model to differentiate the spike parameters between mouse models for ataxia, dystonia, and tremor. The classifier model correctly predicted mouse phenotypes based on single neuron signatures. Spike signatures were shared across etiologically distinct but phenotypically similar disease models. Mimicking these pathophysiological spike signatures with optogenetics induced the predicted motor impairments in otherwise healthy mice. These data show that distinct spike signatures promote the behavioral presentation of cerebellar diseases.

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Section: Methodsmentioning

confidence: 99%

Section: Spike Sorting and Analysesmentioning

confidence: 99%

Section: Supervised Classifier Learnermentioning

confidence: 99%

Section: Supervised Classifier Learnermentioning

confidence: 99%

See 2 more Smart Citations

Cerebellar nuclei cells produce distinct pathogenic spike signatures in mouse models of ataxia, dystonia, and tremor

Heijden

Brown

Kizek

et al. 2023

Preprint

Self Cite

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show abstract

“…Using these criteria, we have consistently been able to target the cerebellar nuclei [ 75 ]. Only traces with clearly identifiable complex spikes were included for Purkinje cells and, for all cells, only those with sufficiently long and stable recording times (113 ± 7 s average; minimum = 40 s) with an optimal signal-to-noise ratio were included [ 76 ]. The distribution of cells recorded from each genotype in each condition is described in the figure legends.…”

Section: Methodsmentioning

confidence: 99%

Propranolol Modulates Cerebellar Circuit Activity and Reduces Tremor

Zhou

Heijden

Leon

et al. 2022

Cells

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Tremor is the most common movement disorder. Several drugs reduce tremor severity, but no cures are available. Propranolol, a β-adrenergic receptor blocker, is the leading treatment for tremor. However, the in vivo circuit mechanisms by which propranolol decreases tremor remain unclear. Here, we test whether propranolol modulates activity in the cerebellum, a key node in the tremor network. We investigated the effects of propranolol in healthy control mice and Car8wdl/wdl mice, which exhibit pathophysiological tremor and ataxia due to cerebellar dysfunction. Propranolol reduced physiological tremor in control mice and reduced pathophysiological tremor in Car8wdl/wdl mice to control levels. Open field and footprinting assays showed that propranolol did not correct ataxia in Car8wdl/wdl mice. In vivo recordings in awake mice revealed that propranolol modulates the spiking activity of control and Car8wdl/wdl Purkinje cells. Recordings in cerebellar nuclei neurons, the targets of Purkinje cells, also revealed altered activity in propranolol-treated control and Car8wdl/wdl mice. Next, we tested whether propranolol reduces tremor through β1 and β2 adrenergic receptors. Propranolol did not change tremor amplitude or cerebellar nuclei activity in β1 and β2 null mice or Car8wdl/wdl mice lacking β1 and β2 receptor function. These data show that propranolol can modulate cerebellar circuit activity through β-adrenergic receptors and may contribute to tremor therapeutics.

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Glutamatergic cerebellar neurons differentially contribute to the acquisition of motor and social behaviors

et al. 2023

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Insults to the developing cerebellum can cause motor, language, and social deficits. Here, we investigate whether developmental insults to different cerebellar neurons constrain the ability to acquire cerebellar-dependent behaviors. We perturb cerebellar cortical or nuclei neuron function by eliminating glutamatergic neurotransmission during development, and then we measure motor and social behaviors in early postnatal and adult mice. Altering cortical and nuclei neurons impacts postnatal motor control and social vocalizations. Normalizing neurotransmission in cortical neurons but not nuclei neurons restores social behaviors while the motor deficits remain impaired in adults. In contrast, manipulating only a subset of nuclei neurons leaves social behaviors intact but leads to early motor deficits that are restored by adulthood. Our data uncover that glutamatergic neurotransmission from cerebellar cortical and nuclei neurons differentially control the acquisition of motor and social behaviors, and that the brain can compensate for some but not all perturbations to the developing cerebellum.

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Influence of data sampling methods on the representation of neural spiking activity in vivo

Cited by 8 publications

References 111 publications

Cerebellar nuclei cells produce distinct pathogenic spike signatures in mouse models of ataxia, dystonia, and tremor

Cerebellar nuclei cells produce distinct pathogenic spike signatures in mouse models of ataxia, dystonia, and tremor

Propranolol Modulates Cerebellar Circuit Activity and Reduces Tremor

Glutamatergic cerebellar neurons differentially contribute to the acquisition of motor and social behaviors

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