Locomotor activity modulates associative learning in mouse cerebellum

Albergaria, Catarina; Silva, N Tatiana; Pritchett, Dominique L.; Carey, Megan R.

doi:10.1038/s41593-018-0129-x

Cited by 97 publications

(149 citation statements)

References 67 publications

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“…Our results are also consistent with studies demonstrating that behavioral state can modulate both perceptual ability, neuronal activity, and motor learning in mice 28,29,32 . The cellular mechanisms of for this effect remain unclear, with potential contributions from neuromodulatory systems 31,42,43 and top-down feedback from other cortical regions and engagement of local inhibitory circuits 44,45 .…”

Section: Discussionsupporting

confidence: 92%

“…Moreover, CPn (but not CSt) layer 5 PNs significantly encoded both sensory and behavioral information, and their activity was necessary for normal task performance. These findings are consistent with a model in which corticopontine projections provide a di-synaptic relay of visual signals to the cerebellum, where synaptic plasticity is thought to drive the association between conditioned and unconditioned stimuli 25,32,39 . Thus, cortical neurons are organized into physically interspersed but functionally distinct networks that can differentially participate in sensory-guided behavior.…”

Section: Discussionsupporting

confidence: 89%

“…Locomotion was also correlated with larger CR magnitude (Extended Data Fig. 1, Extended Data Table 1), consistent with state-dependent modulation of cerebellar motor control 32 . Notably, similar results were seen for pupil dilation (Extended Data Fig.…”

Section: Resultssupporting

confidence: 66%

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Layer 5 circuits in V1 differentially control visuomotor behavior

Tang¹,

Higley²

2019

Preprint

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Sensory areas of the mammalian neocortex are thought to act as distribution hubs, transmitting information about the external environment to various cortical and subcortical structures in order to generate adaptive behavior. However, the exact role of cortical circuits in sensory perception remains unclear. Within primary visual cortex (V1), various populations of pyramidal neurons (PNs) send axonal projections to distinct targets, suggesting multiple cellular networks that may be independently engaged during the generation of behavior. Here, we investigated whether PN subpopulations differentially support sensory-guided performance by training mice in a visual detection task based on eyeblink conditioning. Applying 2-photon calcium imaging and optogenetic manipulation of anatomically-defined PNs in behaving animals, we show that layer 5 corticopontine neurons strongly encode task information and are selectively necessary for performance. These results contrast with recent observations of operant behavior showing a limited role for the neocortex in sensory detection. Instead, our findings support a model in which target-specific cortical subnetworks form the basis for adaptive behavior by directing relevant information to downstream brain areas. Overall, this work highlights the potential for neurons to form physically interspersed but functionally segregated networks capable of parallel, independent control of perception and behavior.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 89%

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Layer 5 circuits in V1 differentially control visuomotor behavior

Tang¹,

Higley²

2019

Preprint

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“…During active states when NE is likely to be released (Reimer et al, 2016), reduced GoC activity could aid the transfer of information from MFs to GCs, improving the reliability of firing at PF-Purkinje cell synapses, facilitating long-term plasticity and speeding learning. This hypothesis is supported by the fact that learning in the cerebellum is facilitated by locomotion (Albergaria et al, 2018) which is known to be correlated to an increase in arousal and the release of NE (Reimer et al, 2016). Our results showing that NE has a powerful effect on the gain of the inhibitory network in the cerebellar input layer, therefore has a number of important implications for cerebellar function.…”

Section: Implications For Sensorimotor Processing and Learning In Thesupporting

confidence: 73%

Norepinephrine controls the gain of the inhibitory circuit in the cerebellar input layer

Lanore¹,

Rothman²,

Coyle³

et al. 2019

Preprint

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Golgi cells (GoCs) are the main inhibitory interneurons in the input layer of the cerebellar cortex and are electrically coupled together, forming syncytia. GoCs control the excitability of granule cells (GCs) through feedforward, feedback and spillovermediated inhibition. The GoC circuit therefore plays a central role in determining how sensory and motor information is transformed as it flows through the cerebellar input layer. Recent work has shown that GCs are activated when animals perform active behaviours, but the underlying mechanisms remain poorly understood. Norepinephrine (NE), also known as noradrenaline, is a powerful modulator of network function during active behavioral states and the axons of NE-releasing neurons in the locus coeruleus innervate the cerebellar cortex. Here we show that NE hyperpolarizes the GoC membrane potential, decreases spontaneous firing and reduces the gain of the spike frequency versus input-current relationship. The GoC membrane hyperpolarization can be mimicked with an α2-noradrenergic agonist, inhibited with a specific α2 antagonist and is abolished when G protein-coupled inwardly-rectifying potassium (GIRK) channels are blocked. Moreover, NE reduces the effective electrical coupling between GoCs through a persistent sodium current (INaP)-dependent mechanism. Our results suggest that NE controls the gain of the GoC inhibitory circuit by modulating membrane conductances that act to reduce membrane excitability and decrease electrical coupling. These mechanisms appear configured to reduce the level of GoC inhibition onto GCs during active behavioural states.

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“…It is well established that the acquisition and expression of DEC both depend on the cerebellum [3][4][5][6][7][8][9][10][11][12][13][14] . The well-defined modular topographical circuitry of the cerebellum provides a unique entry for studying the contribution of specific cerebellar cortical and nuclear regions to sensorimotor tasks.…”

Section: Introductionmentioning

confidence: 99%

A Novel FN-MdV Pathway and Its Role in Cerebellar Multimodular Control of Sensorimotor Behavior

Wang

Ren

et al. 2020

Preprint

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The cerebellum is crucial for various associative sensorimotor behaviors. Delay eyeblink conditioning (DEC) depends on the simplex lobule-interposed nucleus (IN) pathway, yet it is unclear how other cerebellar modules cooperate during this task. Here, we demonstrate the contribution of the vermis-fastigial nucleus (FN) pathway in controlling DEC. We found that task-related modulations in vermal Purkinje cells and FN neurons predict conditioned responses (CRs). Coactivation of the FN and the IN allows for the generation of proper motor commands for CRs, but only FN output fine-tunes unconditioned responses. The vermis-FN pathway launches its signal via the contralateral ventral medullary reticular nucleus, which converges with the command from the simplex-IN pathway onto facial motor neurons. We propose that the IN pathway specifically drives CRs whereas the FN pathway modulates the amplitudes of eyelid closure during DEC. Thus, associative sensorimotor task optimization requires synergistic modulation of different olivocerebellar modules that provide unique contributions.

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Locomotor activity modulates associative learning in mouse cerebellum

Cited by 97 publications

References 67 publications

Layer 5 circuits in V1 differentially control visuomotor behavior

Layer 5 circuits in V1 differentially control visuomotor behavior

Norepinephrine controls the gain of the inhibitory circuit in the cerebellar input layer

A Novel FN-MdV Pathway and Its Role in Cerebellar Multimodular Control of Sensorimotor Behavior

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