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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.

Cancer cachexia is a multifactorial syndrome characterized by a progressive loss of skeletal muscle mass, along with adipose tissue wasting, systemic inflammation and other metabolic abnormalities leading to functional impairment. Cancer cachexia has long been recognized as a direct cause of complications in cancer patients, reducing quality of life and worsening disease outcomes. Some related conditions, like sarcopenia (age‐related muscle wasting), anorexia (appetite loss) and asthenia (reduced muscular strength and fatigue), share some key features with cancer cachexia, such as weakness and systemic inflammation. Understanding the interplay and the differences between these conditions is critical to advance basic and translational research in this field, improving the accuracy of diagnosis and contributing to finally achieve effective therapies for affected patients.

Dedicated neuronal circuits mediate execution, choice, and coordination of body action Movement is the most common final output of nervous system activity and is essential for survival. But what makes this seemingly trivial statement so scientifically challenging? Neurons that contribute to when and how our body moves are distributed throughout the nervous system. Thus, even a simple movement such as arm flexion requires the coordinated activation of many different neuronal populations across multiple brain regions. A key question is how the nervous system produces diverse and precise actions aligned with the organisms' behavioral needs. These processes are affected in diseases such as Parkinson's or Huntington's, in which aberrant motor behavior dominates. Recent studies are transformative in how we think about the control of movement. A common denominator of these studies is that brain regions that contribute to motor behavior can no longer be considered as interacting boxes. Instead, deep circuit-level insight based on specific neuronal populations emerges as being critical to revealing motor system organization and understanding its function. It is likely that insights at this level can also help to design more specific and direct interventions for diseases of the motor system and neuroprosthetics applied after injuries.

The authors trained mice to perform rapid action sequences while recording from neurons in the direct and indirect basal ganglia pathways. In addition to neurons whose activity reflected the start or stop of a sequence, they identified neurons that displayed sustained activity or inhibition throughout an entire action sequence. Chunking allows the brain to efficiently organize memories and actions. Although basal ganglia circuits have been implicated in action chunking, little is known about how individual elements are concatenated into a behavioral sequence at the neural level. Using a task in which mice learned rapid action sequences, we uncovered neuronal activity encoding entire sequences as single actions in basal ganglia circuits. In addition to neurons with activity related to the start/stop activity signaling sequence parsing, we found neurons displaying inhibited or sustained activity throughout the execution of an entire sequence. This sustained activity covaried with the rate of execution of individual sequence elements, consistent with motor concatenation. Direct and indirect pathways of basal ganglia were concomitantly active during sequence initiation, but behaved differently during sequence performance, revealing a more complex functional organization of these circuits than previously postulated. These results have important implications for understanding the functional organization of basal ganglia during the learning and execution of action sequences.

Shifting between goal-directed and habitual actions allows for efficient and flexible decision making. Here we demonstrate a novel, within-subject instrumental lever-pressing paradigm, in which mice shift between goal-directed and habitual actions. We identify a role for orbitofrontal cortex (OFC) in actions following outcome revaluation, and confirm that dorsal medial (DMS) and lateral striatum (DLS) mediate different action strategies. Simultaneous in vivo recordings of OFC, DMS and DLS neuronal ensembles during shifting reveal that the same neurons display different activities depending on whether presses are goal-directed or habitual, with DMS and OFC becoming more and DLS less engaged during goal-directed actions. Importantly, the magnitude of neural activity changes in OFC following changes in outcome value positively correlates with the level of goal-directed behavior. Chemogenetic inhibition of OFC disrupts goal-directed actions, whereas optogenetic activation of OFC specifically increases goal-directed pressing. These results also reveal a role for OFC in action revaluation, which has implications for understanding compulsive behavior. Interactions between corticostriatal circuits are implicated in the shifts between habit- and goal-directed actions. Gremel and Costa show that the orbital frontal cortex and the dorsal medial striatum are necessary for goal-directed actions, whereas the dorsal lateral striatum is necessary for habitual actions.

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.

Postingestive nutrient stimulation conditions food preferences through striatal dopamine and may be associated with blunted brain responses in obesity. In a cross-sectional study, we tested flavor-nutrient conditioning (FNC) with maltodextrin-enriched yogurt, with maltodextrin previously optimized for concentration and dextrose equivalents ( n = 57), and to mask texture cues ( n = 102). After conditioning, healthy volunteers ( n = 52) increased preference for maltodextrin-paired (+102 kcal, CS + ), relative to control (+1.8 kcal, CS - ) flavors, as assessed according to intake, but not pleasantness. In a clinical study ( n = 61), behavioral conditioning without effects on pleasantness was confirmed across pre-bariatric candidates with obesity, weight-stable post-surgery patients, and healthy controls, without significant differences between groups. Striatal dopamine D2-like receptor (DD2lR) availability, assessed with [ 123 I]IBZM SPECT, was reduced in the obesity group and strongly correlated with conditioning strength and a measure of restrained eating in patients with gastric bypass. These results show that postingestive nutrient stimulation influences human food choices through behavioral reinforcement, and is conserved in obesity and after bariatric surgery. Trial Registration: ISRCTN17965026 : Dopaminergic neurotransmission in dietary learning and obesity.

Many models of motor control emphasize the role of sensorimotor cortex in movement, principally through the projections that corticospinal neurons (CSNs) make to the spinal cord. Additionally, CSNs possess expansive supraspinal axon collaterals, the functional organization of which is largely unknown. Using anatomical and electrophysiological circuit-mapping techniques in the mouse, we reveal dorsolateral striatum as the preeminent target of CSN collateral innervation. We found that this innervation is biased so that CSNs targeting different striatal pathways show biased targeting of spinal cord circuits. Contrary to more conventional perspectives, CSNs encode not only individual movements, but also information related to the onset and offset of motor sequences. Furthermore, similar activity patterns are broadcast by CSN populations targeting different striatal circuits. Our results reveal a logic of coordinated connectivity between forebrain and spinal circuits, where separate CSN modules broadcast similarly complex information to downstream circuits, suggesting that differences in postsynaptic connectivity dictate motor specificity. The authors detail principles underlying the innervation of spinal and striatal circuits by populations of corticospinal neurons, and characterize the behavioral information broadcast through this motor control network.

Oceans are a vast source of natural substances. In them, we find various compounds with wide biotechnological and biomedical applicabilities. The exploitation of the sea as a renewable source of biocompounds can have a positive impact on the development of new systems and devices for biomedical applications. Marine polysaccharides are among the most abundant materials in the seas, which contributes to a decrease of the extraction costs, besides their solubility behavior in aqueous solvents and extraction media, and their interaction with other biocompounds. Polysaccharides such as alginate, carrageenan and fucoidan can be extracted from algae, whereas chitosan and hyaluronan can be obtained from animal sources. Most marine polysaccharides have important biological properties such as biocompatibility, biodegradability, and anti-inflammatory activity, as well as adhesive and antimicrobial actions. Moreover, they can be modified in order to allow processing them into various shapes and sizes and may exhibit response dependence to external stimuli, such as pH and temperature. Due to these properties, these biomaterials have been studied as raw material for the construction of carrier devices for drugs, including particles, capsules and hydrogels. The devices are designed to achieve a controlled release of therapeutic agents in an attempt to fight against serious diseases, and to be used in advanced therapies, such as gene delivery or regenerative medicine.

Residual diatomaceous earth (RDE) from winemaking activities is a rich and currently underexploited source of phenolic compounds which ought to be recycled from the perspective of circular bioeconomy. In this work, we demonstrate the feasibility of molecularly imprinted polymers (MIPs) for the enrichment of quercetin, a flavonoid at a fairly high content in residual diatomaceous earth. These MIPs were synthesized through free radical polymerization. FTIR confirmed the integration of the functional monomers into the polymeric chains. Batch adsorption experiments were used to assess the retention and selectivity of those MIPs towards quercetin. Commercial resins were compared with the synthesized materials using the same procedures. These adsorption experiments allowed the selection of the best performing MIP for the valorization of RDE extract. This treatment consisted of saturating the selected MIP with the extract and then desorbing the retained compounds using solvents of selected compositions. The desorbed fractions were analyzed using liquid chromatography, and the results demonstrated an increase in quercetin’s fractional area from 5% in the RDE extract to more than 40% in some fractions, which is roughly an eightfold enrichment of quercetin. Moreover, other flavonoids of close chemical structure to quercetin have been rather retained and enriched by the MIP.