A midbrain - thalamus - cortex circuit reorganizes cortical dynamics to initiate planned movement

Inagaki, Hiroki; Chen, S; Mc, Ridder; Sah, Pankaj; N, Li; Yang, Zidan; Hasanbegovic, Hana; Cr, Gerfen; Svoboda, Karel

doi:10.1101/2020.12.16.423127

Cited by 6 publications

(4 citation statements)

References 107 publications

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“…(behaviour) Activating MRN/PPN terminals in the ipsilateral ALM-projecting thalamus, even unilaterally, did not bias licking in one direction or another, but triggered licking in a direction appropriate to the prior stimulus (Inagaki et al, 2020).…”

Section: Appendix 3: Triggered Behaviours -Pursuit and Escapementioning

confidence: 94%

“…(anatomy / behaviour) MRN neurons projecting to the thalamus and medulla are separate populations, and activation of the thalamus projectors does not bias movement direction (Inagaki et al, 2020).…”

Section: Midbrain Reticular Nucleus (Mrn)mentioning

confidence: 99%

“…(physiology) Neurons in the MRN/pedunculopontine nucleus (PPN) respond after the onset of a cue instructing the mouse to produce a lick, the direction of which was contingent on a prior stimulus (Inagaki et al, 2020).…”

Section: Appendix 3: Triggered Behaviours -Pursuit and Escapementioning

confidence: 99%

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Functional Organisation of the Mouse Superior Colliculus

Wheatcroft¹,

Saleem²,

Solomon³

2021

Preprint

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The superior colliculus (SC) is a highly conserved area of the mammalian midbrain that is widely implicated in the organisation and control of behaviour. SC receives input from a large number of brain areas, and provides outputs to a large number of areas. The convergence and divergence of anatomical connections with different areas and systems provides challenges for understanding how SC contributes to behaviours. Recent work in mouse has provided large anatomical datasets, and a wealth of new data from experiments that identify and manipulate different cells within SC, and its inputs and outputs. These data offer an opportunity to better understand the functional roles of SC. However, some of the observations appear, at first sight, to be contradictory. Here we review this recent work and suggest a simple framework which can capture the observations, and that requires only a small change to previous models. Specifically, the functional organisation of SC can be explained by supposing that three largely distinct circuits support three largely distinct classes of behaviour - arrest, turning towards, and the triggering of escape or pursuit. These behavioural classes are supported by the optic, intermediate and deep layers respectively.

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Section: Appendix 3: Triggered Behaviours -Pursuit and Escapementioning

confidence: 94%

Section: Midbrain Reticular Nucleus (Mrn)mentioning

confidence: 99%

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Functional Organisation of the Mouse Superior Colliculus

Wheatcroft¹,

Saleem²,

Solomon³

2021

Preprint

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“…Yet there is increasing experimental evidence that covariance is often not stable across tasks. Covariance changes dramatically when cycling forward versus backward (Russo et al, 2018), when using one arm versus another (Ames and Churchland, 2019), when preparing versus moving (Kaufman et al, 2014;Elsayed et al, 2016;Inagaki et al, 2020), when reaching versus walking (Miri et al, 2017), and when co-contracting versus alternating muscle activity (Warriner et al, under review). Thus, in a new task, there is no guarantee the high-variance dimensions will be the same or will show the same correlations with kinematics.…”

Section: Introductionmentioning

confidence: 99%

Cortical Control of Virtual Self-Motion Using Task-Specific Subspaces

et al. 2021

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Brain-machine interfaces (BMIs) for reaching have enjoyed continued performance improvements, yet there remains significant need for BMIs that control other movement classes. Recent scientific findings suggest that the intrinsic covariance structure of neural activity depends strongly on movement class, potentially necessitating different decode algorithms across classes. To address this possibility, we developed a self-motion BMI based on cortical activity as monkeys cycled a hand-held pedal to progress along a virtual track. Unlike during reaching, we found no high-variance dimensions that directly correlated with to-be-decoded variables. This was due to no neurons having consistent correlations between their responses and kinematic variables. Yet we could decode a single variable-self-motion-by nonlinearly leveraging structure that spanned multiple high-variance neural dimensions. Resulting online BMI-control success rates approached those during manual control. These findings make two broad points regarding how to build decode algorithms that harmonize with the empirical structure of neural activity in motor cortex. First, even when decoding from the same cortical region (e.g., arm-related motor cortex), different movement classes may need to employ very different strategies. Although correlations between neural activity and hand velocity are prominent during reaching tasks, they are not a fundamental property of motor cortex and cannot be counted on to be present in general. Second, although one generally desires a low-dimensional readout, it can be beneficial to leverage a multidimensional high-variance subspace. Fully embracing this approach requires highly nonlinear approaches tailored to the task at hand, but can produce near-native levels of performance.

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Targeted activation of midbrain neurons restores locomotor function in mouse models of parkinsonism

Masini

Kiehn

2022

Nat Commun

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The pedunculopontine nucleus (PPN) is a locomotor command area containing glutamatergic neurons that control locomotor initiation and maintenance. These motor actions are deficient in Parkinson’s disease (PD), where dopaminergic neurodegeneration alters basal ganglia activity. Being downstream of the basal ganglia, the PPN may be a suitable target for ameliorating parkinsonian motor symptoms. Here, we use in vivo cell-type specific PPN activation to restore motor function in two mouse models of parkinsonism made by acute pharmacological blockage of dopamine transmission. With a combination of chemo- and opto-genetics, we show that excitation of caudal glutamatergic PPN neurons can normalize the otherwise severe locomotor deficit in PD, whereas targeting the local GABAergic population only leads to recovery of slow locomotion. The motor rescue driven by glutamatergic PPN activation is independent of activity in nearby locomotor promoting glutamatergic Cuneiform neurons. Our observations point to caudal glutamatergic PPN neurons as a potential target for neuromodulatory restoration of locomotor function in PD.

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A midbrain - thalamus - cortex circuit reorganizes cortical dynamics to initiate planned movement

Cited by 6 publications

References 107 publications

Functional Organisation of the Mouse Superior Colliculus

Functional Organisation of the Mouse Superior Colliculus

Cortical Control of Virtual Self-Motion Using Task-Specific Subspaces

Targeted activation of midbrain neurons restores locomotor function in mouse models of parkinsonism

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