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Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations 1 , 2 , despite evidence for concentric functional zones 3 and maps of complex actions 4 . Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action 5 and physiological control 6 , arousal 7 , errors 8 and pain 9 . This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions 4 and connectivity to internal organs 10 such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate–isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement. Functional MRI studies across ages show that the classic homunculus of the motor cortex in humans is in fact discontinuous, alternating with action control-linked regions termed the somato-cognitive action network.

The striatum is essential for learning which actions lead to reward and for implementing those actions. Decades of experimental and theoretical work have led to several influential theories and hypotheses about how the striatal circuit mediates these functions. However, owing to technical limitations, testing these hypotheses rigorously has been difficult. In this Review, we briefly describe some of the classic ideas of striatal function. We then review recent studies in rodents that take advantage of optical and genetic methods to test these classic ideas by recording and manipulating identified cell types within the circuit. This new body of work has provided experimental support of some longstanding ideas about the striatal circuit and has uncovered critical aspects of the classic view that are incorrect or incomplete.The striatum is crucial for learning and decision-making. Cox and Witten provide an updated overview of the roles of different parts of the striatal circuit in learning and decision-making, showing how recent experiments support and contradict previous models.

The execution and learning of diverse movements involve neuronal networks distributed throughout the nervous system. The brainstem and basal ganglia are key for processing motor information. Both harbour functionally specialized populations stratified on the basis of axonal projections, synaptic inputs and gene expression, revealing a correspondence between circuit anatomy and function at a high level of granularity. Neuronal populations within both structures form multistep processing chains dedicated to the execution of specific movements; however, the connectivity and communication between these two structures is only just beginning to be revealed. The brainstem and basal ganglia are also embedded into wider networks and into systems-level loops. Important networking components include broadcasting neurons in the cortex, cerebellar output neurons and midbrain dopaminergic neurons. Action-specific circuits can be enhanced, vetoed, work in synergy or competition with others, or undergo plasticity to allow adaptive behaviour. We propose that this highly specific organization of circuits in the motor system is a core ingredient for supporting behavioural specificity, and at the same time for providing an adequate substrate for behavioural flexibility.In this Review, Arber and Costa discuss the anatomical and functional specificity of circuitry essential for executing diverse body movements. They focus on specific neuronal populations in the brainstem and the basal ganglia, and the integration of these circuits into systems-level networks that afford flexibility and learning.

The basal ganglia and the cerebellum are considered to be distinct subcortical systems that perform unique functional operations. The outputs of the basal ganglia and the cerebellum influence many of the same cortical areas but do so by projecting to distinct thalamic nuclei. As a consequence, the two subcortical systems were thought to be independent and to communicate only at the level of the cerebral cortex. Here, we review recent data showing that the basal ganglia and the cerebellum are interconnected at the subcortical level. The subthalamic nucleus in the basal ganglia is the source of a dense disynaptic projection to the cerebellar cortex. Similarly, the dentate nucleus in the cerebellum is the source of a dense disynaptic projection to the striatum. These observations lead to a new functional perspective that the basal ganglia, the cerebellum and the cerebral cortex form an integrated network. This network is topographically organized so that the motor, cognitive and affective territories of each node in the network are interconnected. This perspective explains how synaptic modifications or abnormal activity at one node can have network-wide effects. A future challenge is to define how the unique learning mechanisms at each network node interact to improve performance.

The cortico–basal ganglia–thalamo–cortical loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behaviour, and the natural history of many neurological and neuropsychiatric disorders. Classically, this network is conceptualized to contain three information channels: motor, limbic and associative 1 – 4 . Yet this three-channel view cannot explain the myriad functions of the basal ganglia. We previously subdivided the dorsal striatum into 29 functional domains on the basis of the topography of inputs from the entire cortex 5 . Here we map the multi-synaptic output pathways of these striatal domains through the globus pallidus external part (GPe), substantia nigra reticular part (SNr), thalamic nuclei and cortex. Accordingly, we identify 14 SNr and 36 GPe domains and a direct cortico-SNr projection. The striatonigral direct pathway displays a greater convergence of striatal inputs than the more parallel striatopallidal indirect pathway, although direct and indirect pathways originating from the same striatal domain ultimately converge onto the same postsynaptic SNr neurons. Following the SNr outputs, we delineate six domains in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify six parallel cortico–basal ganglia–thalamic subnetworks that sequentially transduce specific subsets of cortical information through every elemental node of the cortico–basal ganglia–thalamic loop. Thalamic domains relay this output back to the originating corticostriatal neurons of each subnetwork in a bona fide closed loop. Mesoscale connectomic mapping of the cortico–basal ganglia–thalamic network reveals key architectural and information processing features.

Dopamine neurons are characterized by their response to unexpected rewards, but they also fire during movement and aversive stimuli. Dopamine neuron diversity has been observed based on molecular expression profiles; however, whether different functions map onto such genetic subtypes remains unclear. In this study, we established that three genetic dopamine neuron subtypes within the substantia nigra pars compacta, characterized by the expression of Slc17a6 ( Vglut2 ), Calb1 and Anxa1 , each have a unique set of responses to rewards, aversive stimuli and accelerations and decelerations, and these signaling patterns are highly correlated between somas and axons within subtypes. Remarkably, reward responses were almost entirely absent in the Anxa1 + subtype, which instead displayed acceleration-correlated signaling. Our findings establish a connection between functional and genetic dopamine neuron subtypes and demonstrate that molecular expression patterns can serve as a common framework to dissect dopaminergic functions. The authors establish a connection between functional subtypes and genetic subtypes of dopamine neurons in mice and demonstrate that molecular expression patterns can serve as a common framework to dissect dopaminergic functions.

Key Points Self-grooming is an evolutionarily conserved complex innate behaviour that has a role in hygiene maintenance and other physiological functions. Self-grooming is the most frequently occurring awake behaviour in laboratory rodents. Self-grooming is an important phenotype to study in translational neuroscience, as it may allow the modelling of human diseases that have symptoms similar to, and/or share pathogenetic mechanisms with, aberrant grooming in rodents. Analysing animal self-grooming also has a broader value in the study of neurobiology underlying complex repetitive behaviours, which may be disrupted in certain neurological diseases. In this Review, we discuss the neurobiology of grooming, including its underlying circuitry, genetic mechanisms and pharmacological modulation. We also highlight studies of rodent self-grooming behaviour in models of neuropsychiatric disorders that suggest that it is valuable asset for clinical and translational neuroscience research, including the identification of neural circuits that control complex patterned behaviours. These findings suggest that the study of rodent self-grooming has multiple implications for translational neuroscience, which may extend beyond understanding the self-grooming behaviour itself. Rodents spend a large proportion of their waking time engaged in self-grooming behaviour. In this Review, Kalueff and colleagues describe the characteristics and underlying neural circuitry of rodent self-grooming, and discuss its use as a measure of repetitive behaviour in models of psychiatric disease. Self-grooming is a complex innate behaviour with an evolutionarily conserved sequencing pattern and is one of the most frequently performed behavioural activities in rodents. In this Review, we discuss the neurobiology of rodent self-grooming, and we highlight studies of rodent models of neuropsychiatric disorders — including models of autism spectrum disorder and obsessive compulsive disorder — that have assessed self-grooming phenotypes. We suggest that rodent self-grooming may be a useful measure of repetitive behaviour in such models, and therefore of value to translational psychiatry. Assessment of rodent self-grooming may also be useful for understanding the neural circuits that are involved in complex sequential patterns of action.

Spontaneous animal behaviour is built from action modules that are concatenated by the brain into sequences 1 , 2 . However, the neural mechanisms that guide the composition of naturalistic, self-motivated behaviour remain unknown. Here we show that dopamine systematically fluctuates in the dorsolateral striatum (DLS) as mice spontaneously express sub-second behavioural modules, despite the absence of task structure, sensory cues or exogenous reward. Photometric recordings and calibrated closed-loop optogenetic manipulations during open field behaviour demonstrate that DLS dopamine fluctuations increase sequence variation over seconds, reinforce the use of associated behavioural modules over minutes, and modulate the vigour with which modules are expressed, without directly influencing movement initiation or moment-to-moment kinematics. Although the reinforcing effects of optogenetic DLS dopamine manipulations vary across behavioural modules and individual mice, these differences are well predicted by observed variation in the relationships between endogenous dopamine and module use. Consistent with the possibility that DLS dopamine fluctuations act as a teaching signal, mice build sequences during exploration as if to maximize dopamine. Together, these findings suggest a model in which the same circuits and computations that govern action choices in structured tasks have a key role in sculpting the content of unconstrained, high-dimensional, spontaneous behaviour. Photometric recordings and optogenetic manipulation show that dopamine fluctuations in the dorsolateral striatum in mice modulate the use, sequencing and vigour of behavioural modules during spontaneous behaviour.

The activity of dopamine neurons in the substantia nigra pars compacta before movement initiation affects the probability and vigour of future movements. How dopamine neurons forge future movements Loss of dopamine neurons in a specific area of the brain, the substantia nigra pars compacta (SNc), causes failure to initiate and slowness of movement in patients with Parkinson's disease. Rui Costa and colleagues explore the role of these neurons in movement and reward. In mice, SNc dopamine neurons are transiently active before a self-initiated movement. The neurons affect movement initiation, but they are not selective for specific actions. Manipulation of dopamine neuron activity alters the probability of future movement initiation and the speed of movement, but does not affect ongoing movements. These findings suggest that dopamine signals serve as a general signal for gating and invigorating self-paced movements. Deciding when and whether to move is critical for survival. Loss of dopamine neurons (DANs) of the substantia nigra pars compacta (SNc) in patients with Parkinson’s disease causes deficits in movement initiation and slowness of movement 1 . The role of DANs in self-paced movement has mostly been attributed to their tonic activity, whereas phasic changes in DAN activity have been linked to reward prediction 2 , 3 . This model has recently been challenged by studies showing transient changes in DAN activity before or during self-paced movement initiation 4 , 5 , 6 , 7 . Nevertheless, the necessity of this activity for spontaneous movement initiation has not been demonstrated, nor has its relation to initiation versus ongoing movement been described. Here we show that a large proportion of SNc DANs, which did not overlap with reward-responsive DANs, transiently increased their activity before self-paced movement initiation in mice. This activity was not action-specific, and was related to the vigour of future movements. Inhibition of DANs when mice were immobile reduced the probability and vigour of future movements. Conversely, brief activation of DANs when mice were immobile increased the probability and vigour of future movements. Manipulations of dopamine activity after movement initiation did not affect ongoing movements. Similar findings were observed for the initiation and execution of learned action sequences. These findings causally implicate DAN activity before movement initiation in the probability and vigour of future movements.

The cortex projects to the dorsal striatum topographically 1 , 2 to regulate behaviour 3 – 5 , but spiking activity in the two structures has previously been reported to have markedly different relations to sensorimotor events 6 – 9 . Here we show that the relationship between activity in the cortex and striatum is spatiotemporally precise, topographic, causal and invariant to behaviour. We simultaneously recorded activity across large regions of the cortex and across the width of the dorsal striatum in mice that performed a visually guided task. Striatal activity followed a mediolateral gradient in which behavioural correlates progressed from visual cue to response movement to reward licking. The summed activity in each part of the striatum closely and specifically mirrored activity in topographically associated cortical regions, regardless of task engagement. This relationship held for medium spiny neurons and fast-spiking interneurons, whereas the activity of tonically active neurons differed from cortical activity with stereotypical responses to sensory or reward events. Inactivation of the visual cortex abolished striatal responses to visual stimuli, supporting a causal role of cortical inputs in driving the striatum. Striatal visual responses were larger in trained mice than untrained mice, with no corresponding change in overall activity in the visual cortex. Striatal activity therefore reflects a consistent, causal and scalable topographical mapping of cortical activity. Simultaneous mapping of activity across the cortex and dorsal striatum in mice shows that activity in each part of the striatum precisely mirrors that in topographically associated cortical regions, consistently across behavioural contexts.