Effective training procedure for a simultaneous bimanual movement task in head-fixed mice.

Bimanual movements consist of simultaneous and nonsimultaneous movements. The neural mechanisms of unimanual and nonsimultaneous bimanual movements have been explored in rodent studies through electrophysiological recordings and calcium imaging techniques. However, the neural bases of simultaneous bimanual movements remain poorly understood because of a lack of effective training procedures for such movements in head-fixed rodents.

A cerebello-thalamo-cortical pathway transmits reward-based post-error signals for motor timing correction during learning in male mice.

The cerebellum is critical for motor timing control and error-driven motor learning. To reveal how the cerebellum transmits these process-relevant signals to the premotor cortex, we conducted two-photon calcium imaging of cerebellar-thalamocortical axons in the premotor cortex in male mice during a self-timing lever-pull task that required 1-1.7 s of waiting after cue onset.

Multimodal dataset linking wide-field calcium imaging to behavior changes in operant lever-pull task in mice.

The link between comprehensive behavioral measurements during a behavioral task and brain-wide neuronal activity is an essential strategy to better understand the brain dynamics underlying the emergence of behavior changes. To tackle this, we provide an extensive, multimodal dataset that includes 15 sessions spanning 2 weeks of motor skill learning, in which 25 mice were trained to pull a lever to obtain water rewards. Simultaneous high-speed videography captured body, facial, and eye movements, and environmental parameters were monitored.

Whether or not to act is determined by distinct signals from motor thalamus and orbitofrontal cortex to secondary motor cortex.

"To act or not to act" is a fundamental decision made in daily life. However, it is unknown how the relevant signals are transmitted to the secondary motor cortex (M2), which is the cortical origin of motor initiation. Here, we found that in a decision-making task in male mice, inputs from the thalamus to M2 positively regulated the action while inputs from the lateral part of the orbitofrontal cortex (LO) negatively regulated it.

Predictive reward-prediction errors of climbing fiber inputs integrate modular reinforcement learning with supervised learning.

Although the cerebellum is typically associated with supervised learning algorithms, it also exhibits extensive involvement in reward processing. In this study, we investigated the cerebellum's role in executing reinforcement learning algorithms, with a particular emphasis on essential reward-prediction errors. We employed the Q-learning model to accurately reproduce the licking responses of mice in a Go/No-go auditory-discrimination task.

Integrated information theory reveals the potential role of the posterior parietal cortex in sustaining conditioning responses in classical conditioning tasks.

Classical conditioning is a fundamental associative learning process in which repeated pairings of a conditioned stimulus (CS) with an unconditioned stimulus (US) lead to the CS eliciting a conditioned response (CR). Previous research has identified key neural regions involved in processing reward-predicting cues and mediating licking behavior. However, the mechanisms that sustain high conditioned response rates across repeated sessions remain elusive, particularly regarding how the reward expectation is represented on a session-by-session basis.

Medial prefrontal cortex suppresses reward-seeking behavior with risk of punishment by reducing sensitivity to reward.

Reward-seeking behavior is frequently associated with risk of punishment. There are two types of punishment: positive punishment, which is defined as addition of an aversive stimulus, and negative punishment, involves the omission of a rewarding outcome. Although the medial prefrontal cortex (mPFC) is important in avoiding punishment, whether it is important for avoiding both positive and negative punishment and how it contributes to such avoidance are not clear.

Dynamic organization of cerebellar climbing fiber response and synchrony in multiple functional components reduces dimensions for reinforcement learning.

Cerebellar climbing fibers convey diverse signals, but how they are organized in the compartmental structure of the cerebellar cortex during learning remains largely unclear. We analyzed a large amount of coordinate-localized two-photon imaging data from cerebellar Crus II in mice undergoing 'Go/No-go' reinforcement learning. Tensor component analysis revealed that a majority of climbing fiber inputs to Purkinje cells were reduced to only four functional components, corresponding to accurate timing control of motor initiation related to a Go cue, cognitive error-based learning, reward processing, and inhibition of erroneous behaviors after a No-go cue.

Optical deep-cortex exploration in behaving rhesus macaques.

Two papers published in June 2021 used a two-photon microscope or one-photon miniature microscope to interrogate the motor cortex in behaving macaque monkeys. The imaging was performed over several months, and the direction of natural arm reaching was decoded from the population activity.

Neuronal representations of reward-predicting cues and outcome history with movement in the frontal cortex.

Transformation of sensory inputs to goal-directed actions requires estimation of sensory-cue values based on outcome history. We conduct wide-field and two-photon calcium imaging of the mouse neocortex during classical conditioning with two cues with different water-reward probabilities. Although licking movement dominates the area-averaged activity over the whole dorsal neocortex, the dorsomedial frontal cortex (dmFrC) affects other dorsal frontal cortical activities, and its inhibition extinguishes differences in anticipatory licking between the cues.

Tb-doped fluorescent glass for biology.

Optical investigation and manipulation constitute the core of biological experiments. Here, we introduce a new borosilicate glass material that contains the rare-earth ion terbium(III) (Tb), which emits green fluorescence upon blue light excitation, similar to green fluorescent protein (GFP), and thus is widely compatible with conventional biological research environments. Micropipettes made of Tb-doped glass allowed us to target GFP-labeled cells for single-cell electroporation, single-cell transcriptome analysis (Patch-seq), and patch-clamp recording under real-time fluorescence microscopic control.

Non-action Learning: Saving Action-Associated Cost Serves as a Covert Reward.

"To do or not to do" is a fundamental decision that has to be made in daily life. Behaviors related to multiple "to do" choice tasks have long been explained by reinforcement learning, and "to do or not to do" tasks such as the go/no-go task have also been recently discussed within the framework of reinforcement learning. In this learning framework, alternative actions and/or the non-action to take are determined by evaluating explicitly given (overt) reward and punishment.

Structural dynamics and stability of corticocortical and thalamocortical axon terminals during motor learning.

Synaptic plasticity is the cellular basis of learning and memory. When animals learn a novel motor skill, synaptic modifications are induced in the primary motor cortex (M1), and new postsynaptic dendritic spines relevant to motor memory are formed in the early stage of learning. However, it is poorly understood how presynaptic axonal boutons are formed, eliminated, and maintained during motor learning, and whether long-range corticocortical and thalamocortical axonal boutons show distinct structural changes during learning.

Common marmoset as a model primate for study of the motor control system.

The common marmoset (Callithrix jacchus), a New World monkey, is emerging as a promising animal model for biomedical and neuroscience research. This species shares its basic brain architecture, including the organization of the motor cortical areas and the connections between these and other areas, with humans and other primates. Its small and lissencephalic cerebral cortex is suitable for the application of modern biological techniques.

Arm movements induced by noninvasive optogenetic stimulation of the motor cortex in the common marmoset.

Optogenetics is now a fundamental tool for investigating the relationship between neuronal activity and behavior. However, its application to the investigation of motor control systems in nonhuman primates is rather limited, because optogenetic stimulation of cortical neurons in nonhuman primates has failed to induce or modulate any hand/arm movements. Here, we used a tetracycline-inducible gene expression system carrying CaMKII promoter and the gene encoding a Channelrhodopsin-2 variant with fast kinetics in the common marmoset, a small New World monkey.

Motor learning requires myelination to reduce asynchrony and spontaneity in neural activity.

Myelination increases the conduction velocity in long-range axons and is prerequisite for many brain functions. Impaired myelin regulation or impairment of myelin itself is frequently associated with deficits in learning and cognition in neurological and psychiatric disorders. However, it has not been revealed what perturbation of neural activity induced by myelin impairment causes learning deficits.

Thalamocortical Axonal Activity in Motor Cortex Exhibits Layer-Specific Dynamics during Motor Learning.

The thalamus is the hub through which neural signals are transmitted from the basal ganglia and cerebellum to the neocortex. However, thalamocortical axonal activity during motor learning remains largely undescribed. We conducted two-photon calcium imaging of thalamocortical axonal activity in the motor cortex of mice learning a self-initiated lever-pull task.