Transformation of Cortex-wide Emergent Properties during Motor Learning

Makino, Hiroshi; Ren, Chi; Liu, Haixin; Kim, An Na; Kondapaneni, Neehar; Liu, Xin; Kuzum, Duygu; Komiyama, Takaki

doi:10.1016/j.neuron.2017.04.015

Cited by 237 publications

(325 citation statements)

References 45 publications

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“…Several studies recently addressed the contamination of the blood volume changes on fluorescence signal of calcium indicators like GCaMP (see, for instance, (Ma et al, 2016a;Ma et al, 2016b;Makino et al, 2017;Murphy et al, 2018;Wright et al, 2017)). The recent paper by Ma et al (Ma et al, 2016b) showed that the hemodynamic contribution is slower than the GCaMP6f signal, with an average temporal delay of 0.86 ± 0.05 s (representing the phase shift between neural activity and total hemoglobin concentration).…”

Section: Discussionmentioning

confidence: 99%

Rehabilitation promotes the recovery of structural and functional features of healthy neuronal networks after stroke

Mascaro

Conti

Lai

et al. 2019

Preprint

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Rehabilitation is the most effective treatment for promoting the recovery of motor deficits after stroke.One of the most challenging experimental goals is to unambiguously link brain rewiring to motor recovery prompted by rehabilitative therapy. Here, we investigated which aspects of cortical remodeling are induced by rehabilitation by combining optical imaging and manipulation tools in a mouse model of stroke. We revealed that the stabilization of peri-infarct synaptic contacts fostered by rehabilitation goes along with increased vascular density induced by angiogenesis. Furthermore, we showed the progressive formation of a new motor representation in the peri-infarct area where temporal and spatial features of cortical activation recovered towards pre-stroke condition. In the same animals we observed the reinforcement of inter-hemispheric connectivity after rehabilitation. The present work provides the first evidences that rehabilitation promotes the combined recovery of structural and functional features distinctive of healthy neuronal networks.

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Section: Discussionmentioning

confidence: 99%

Rehabilitation promotes the recovery of structural and functional features of healthy neuronal networks after stroke

Mascaro

Conti

Lai

et al. 2019

Preprint

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“…8) even though the activation threshold was expected to be greater. In fact, it is possible that inhibitory neurons were displaying the unexpected preference [77]. Future studies should investigate the stimulation thresholds (i.e.…”

Section: Biophysics Of the Interaction Of Polarity And Asymmetry On Nmentioning

confidence: 99%

In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice

Steiger

Eles

Ludwig

et al. 2019

Preprint

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250 word maximum Electrical stimulation has been critical in the development of an understanding of brain function and disease. Despite its widespread use and obvious clinical potential, the mechanisms governing stimulation in the cortex remain largely unexplored in the context of pulse parameters. Modeling studies have suggested that modulation of stimulation pulse waveform may be able to control the probability of neuronal activation to selectively stimulate either cell bodies or passing fibers depending on the leading polarity. Thus, asymmetric waveforms with equal charge per phase (i.e. increasing the leading phase duration and proportionately decreasing the amplitude) may be able to activate a more spatially localized or distributed population of neurons if the leading phase is cathodic or anodic, respectively. Here, we use two-photon and mesoscale calcium imaging of GCaMP6s expressed in excitatory pyramidal neurons of male mice to investigate the role of pulse polarity and waveform asymmetry on the spatiotemporal properties of direct neuronal activation with 10 Hz electrical stimulation. We demonstrate that increasing cathodic asymmetry effectively reduces neuronal activation and results in a more spatially localized subpopulation of activated neurons without sacrificing the density of activated neurons around the electrode. Conversely, increasing anodic asymmetry increases the spatial spread of activation and highly resembles spatiotemporal calcium activity induced by conventional symmetric cathodic stimulation. These results suggest that stimulation polarity and asymmetry can be used to modulate the spatiotemporal dynamics of neuronal activity thus increasing the effective parameter space of electrical stimulation to restore sensation and study circuit dynamics.Significance Statement: Electrical stimulation has promise to restore sensation and motor function, as well as treat the symptoms of several neurological disorders. However, the mechanisms responsible for the beneficial effects of stimulation are not fully understood. This work supports modeling predictions by demonstrating that modulation of the stimulation waveform dramatically affects the spatial recruitment and activity level of neurons in vivo. These findings suggest that stimulation waveform symmetry represents a parameter that may be able to increase the dynamic range of stimulation ap-plications. Further characterization of these parameters with frequency, and amplitude could provide further insight into the mechanisms of electrical stimulation.

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“…In order to investigate how causal control over external objects is effected and encoded in mammalian cortex, we trained mice to control a visual feedback cursor using real-time calcium signals recorded with wide-field imaging (largely reflecting the summed spiking activity of local cells (Makino et al, 2017;Clancy et al, 2019).…”

Section: Goal-directed Control Of a Visual Cursor Using Areal Signalsmentioning

confidence: 99%

The sensory representation of causally controlled objects

Clancy

Mrsic-Flogel

2019

Preprint

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Intentional control over external objects is informed by our sensory experience of them, in a continuous dialogue between action and perception.How such control is represented at the sensory level, however, is not understood. Here we devised a brain machine interface (BMI) task that enabled mice to guide a visual cursor to a target location for reward, using activity in brain areas recorded with widefield calcium imaging. Parietal and higher visual cortical regions were more engaged when expert animals controlled the cursor, but not in naïve mice learning the task. Intentional control enhanced responses: single-cell recordings from parietal cortex indicated that the same visual cursor elicited larger responses when mice controlled it than when they passively viewed it. Moreover, neural responses were greater when the cursor was moving towards the target than away from it. Thus, the sensory representation of a causally-controlled object is sensitive to a subject's intention, as well as the object's instantaneous trajectory relative to the subject's goal: potentially strengthening the sensory feedback signal to adjudicating areas for exerting more fluent control.

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Transformation of Cortex-wide Emergent Properties during Motor Learning

Cited by 237 publications

References 45 publications

Rehabilitation promotes the recovery of structural and functional features of healthy neuronal networks after stroke

Rehabilitation promotes the recovery of structural and functional features of healthy neuronal networks after stroke

In vivo microstimulation with cathodic and anodic asymmetric waveforms modulates spatiotemporal calcium dynamics in cortical neuropil and pyramidal neurons of male mice

The sensory representation of causally controlled objects

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