鸣禽前脑基底神经节X区与语言学习

成年鸣禽鸣唱语句的形成和维持依赖于听觉反馈。X区是鸣禽前脑回路的一个重要核团,对鸣禽的发声学习和语言结构的稳定有重要作用。X区在解剖结构、电生理学以及神经化学等方面的特性与哺乳类基底神经节极为相似。对鸣禽前脑X区的研究有助于揭示人类语言学习的中枢机制。本文对近年来鸣禽X区的相关研究进展,包括鸣禽X区的结构特征、电生理特性及神经化学特征予以阐述。     

Conditional visuo-motor learning in primates: a key role for the basal ganglia

Sensory guidance of behavior often involves standard visuo-motor mapping of body movements onto objects and spatial locations. For example, looking at and reaching to grasp a glass of wine requires the mapping of the eyes and hand to the location of the glass in space, as well as the formation of a hand configuration appropriate to the shape of the glass. But our brain is far more than just a standard sensorimotor mapping machine. Through evolution, the brain of advanced mammals, in particular human and non-human primates, has acquired a formidable capacity to construct non-standard, arbitrary mapping using associations between external events and behavioral responses that bear no direct relationship. For example, we have all learned to stop at a red traffic light and to go at a green one, or to wait for a specific tone before dialing a phone number and to hang up when hearing a busy signal. These arbitrary associations are acquired through experience, thereby providing primates with a rich and flexible sensorimotor repertoire. Understanding how they are learned, and how they are recalled and used when the context requires them, has been one of the challenging issues for cognitive neuroscience. Valuable insights have been gained over the last two decades through the convergence of multiple complementary approaches. Human neuropsychology and experimental lesions in monkeys have identified a network of brain structures important for conditional sensorimotor associations, whereas imaging studies in healthy human subjects and electrophysiological recordings in awake monkeys have sought to identify the different functional processes underlying the overall function. The present review focuses on the contribution of a network linking the prefrontal cortex, basal ganglia, and dorsal premotor cortex, with special emphasis on results from recording experiments in monkeys. We will first review data pointing to a specific contribution of each component of the network to the performance of well-learned arbitrary visuo-motor associations, as well as data suggesting how novel associations are formed. Then we will propose a model positing that each component of the fronto-striatal network makes a specific contribution to the formation and/or execution of sensorimotor associations. In this model, the basal ganglia are thought to play a key role in linking the sensory, motor, and reward information necessary for arbitrary mapping.     

Complementary roles of basal ganglia and cerebellum in learning and motor control

The classical notion that the basal ganglia and the cerebellum are dedicated to motor control has been challenged by the accumulation of evidence revealing their involvement in non-motor, cognitive functions. From a computational viewpoint, it has been suggested that the cerebellum, the basal ganglia, and the cerebral cortex are specialized for different types of learning: namely, supervised learning, reinforcement learning and unsupervised learning, respectively. This idea of learning-oriented specialization is helpful in understanding the complementary roles of the basal ganglia and the cerebellum in motor control and cognitive functions.     

Endocannabinoids and basal ganglia functionality

In recent years, our knowledge on the cannabinoid pharmacology has shown a significant rise in terms of both quantity (more compounds and more targets) and quality (more selective compounds). This allows to consider cannabinoids and related compounds as a promising new line of research for therapeutic treatment of a variety of conditions, such as brain injury, chronic pain, glaucoma, asthma, cancer and AIDS-associated effects and other pathologies. Motor disorders are another promising field for the therapeutic application of cannabinoid-related compounds, since the control of movement is one of the more relevant physiological roles of the endocannabinoid transmission in the brain. There are two pathologies, Parkinson's disease and Huntington's chorea, which are particularly interesting from a clinical point of view due to the direct relationship of endocannabinoids and their receptors with neurons that degenerate in those disorders. However, other neurological pathologies, such as Alzheimer's disease or multiple sclerosis, which are not motor disorders in origin, but present a strong alteration in the control of movement, have also been a subject of interesting research for a cannabinoid therapy. This review will summarize our current knowledge on the role of these endogenous substances in the control of movement and, in particular, on the possible therapeutic usefulness of these compounds in the treatment of motor pathologies.     

Rhythmic cortical neurons increase their oscillations and sculpt basal ganglia signaling during motor learning

The function and modulation of neural circuits underlying motor skill may involve rhythmic oscillations (Feller, 1999 ; Marder and Goaillard, 2006 ; Churchland et al., 2012 ). In the proposed pattern generator for birdsong, the cortical nucleus HVC, the frequency and power of oscillatory bursting during singing increases with development (Crandall et al., 2007 ; Day et al., 2009 ). We examined the maturation of cellular activity patterns that underlie these changes. Single unit ensemble recording combined with antidromic identification (Day et al., 2011 ) was used to study network development in anesthetized zebra finches. Autocovariance quantified oscillations within single units. A subset of neurons oscillated in the theta/alpha/mu/beta range (8–20 Hz), with greater power in adults compared to juveniles. Across the network, the normalized oscillatory power in the 8–20 Hz range was greater in adults than juveniles. In addition, the correlated activity between rhythmic neuron pairs increased with development. We next examined the functional impact of the oscillators on the output neurons of HVC. We found that the firing of oscillatory neurons negatively correlated with the activity of cortico‐basal ganglia neurons (HVC_Xs), which project to Area X (the song basal ganglia). If groups of oscillators work together to tonically inhibit and precisely control the spike timing of adult HVC_Xs with coordinated release from inhibition, then the activity of HVC_Xs in juveniles should be decreased relative to adults due to uncorrelated, tonic inhibition. Consistent with this hypothesis, HVC_Xs had lower activity in juveniles. These data reveal network changes that shape cortical‐to‐basal ganglia signaling during motor learning. © 2013 Wiley Periodicals, Inc. Develop Neurobiol 73: 754–768, 2013     

The role of the basal ganglia in exploration in a neural model based on reinforcement learning

We present a computational model of basal ganglia as a key player in exploratory behavior. The model describes exploration of a virtual rat in a simulated water pool experiment. The virtual rat is trained using a reward-based or reinforcement learning paradigm which requires units with stochastic behavior for exploration of the system's state space. We model the Subthalamic Nucleus-Globus Pallidus externa (STN-GPe) segment of the basal ganglia as a pair of neuronal layers with oscillatory dynamics, exhibiting a variety of dynamic regimes such as chaos, traveling waves and clustering. Invoking the property of chaotic systems to explore state-space, we suggest that the complex exploratory dynamics of STN-GPe system in conjunction with dopamine-based reward signaling from the Substantia Nigra pars compacta (SNc) present the two key ingredients of a reinforcement learning system.     

Uncertainty–guided learning with scaled prediction errors in the basal ganglia

To accurately predict rewards associated with states or actions, the variability of observations has to be taken into account. In particular, when the observations are noisy, the individual rewards should have less influence on tracking of average reward, and the estimate of the mean reward should be updated to a smaller extent after each observation. However, it is not known how the magnitude of the observation noise might be tracked and used to control prediction updates in the brain reward system. Here, we introduce a new model that uses simple, tractable learning rules that track the mean and standard deviation of reward, and leverages prediction errors scaled by uncertainty as the central feedback signal. We show that the new model has an advantage over conventional reinforcement learning models in a value tracking task, and approaches a theoretic limit of performance provided by the Kalman filter. Further, we propose a possible biological implementation of the model in the basal ganglia circuit. In the proposed network, dopaminergic neurons encode reward prediction errors scaled by standard deviation of rewards. We show that such scaling may arise if the striatal neurons learn the standard deviation of rewards and modulate the activity of dopaminergic neurons. The model is consistent with experimental findings concerning dopamine prediction error scaling relative to reward magnitude, and with many features of striatal plasticity. Our results span across the levels of implementation, algorithm, and computation, and might have important implications for understanding the dopaminergic prediction error signal and its relation to adaptive and effective learning.     

Sea turtles: old viruses and new tricks

Recent years have seen an inexplicable increase in the frequency of an appalling disease in sea turtles: fibropapillomatosis, which is likely caused by a herpesvirus and causes tumors to grow throughout the turtle's body. New research has led to the disturbing conclusion that recent, human-induced environmental changes are responsible.     

tRNAs: new tricks from old dogs

tRNA biology has lately seen a revival with the discovery of tRNA cleavage products as mediators of stress responses. In this issue of The EMBO Journal, Blanco et al now report that tRNA methylation, by protecting from cleavage, is relevant for normal brain development. The versatility of tRNA is further emphasized by a recent study in Cell that uncovered differential expression of tRNAs as a means to accustom codon usage bias to the needs in proliferating versus differentiating cells.     

Nucleostemin: A latecomer with new tricks

Nucleostemin was first identified in neural stem cells and has become a focus of research in cell cycle control, tumorigenesis and cellular senescence. As the biology of nucleostemin begins to be unveiled in multiple species, an ensuing task is to resolve the apparent differences between the functions of mammalian and invertebrate nucleostemin and its homologues, an issue of pressing interest given the role of nucleostemin in stem cell self-renewal and tissue regeneration. A genome-wide search reveals that nucleostemin and its closest homologue, GNL3L, only emerge as separate genes in vertebrates and possess conserved protein sequences as evolution proceeded to the Mammalia. The invertebrate orthologue of nucleostemin and GNL3L resembles GNL3L more than it does nucleostemin in function, raising the idea that nucleostemin acquires new properties while GNL3L inherits an evolutionarily fixed role, and that the birth of nucleostemin may signify the appearance of new functional features in the vertebrate lineage.     

Molecular microcircuitry underlies functional specification in a basal ganglia circuit dedicated to vocal learning

Similarities between speech and birdsong make songbirds advantageous for investigating the neurogenetics of learned vocal communication--a complex phenotype probably supported by ensembles of interacting genes in cortico-basal ganglia pathways of both species. To date, only FoxP2 has been identified as critical to both speech and birdsong. We performed weighted gene coexpression network analysis on microarray data from singing zebra finches to discover gene ensembles regulated during vocal behavior. We found ～2,000 singing-regulated genes comprising three coexpression groups unique to area X, the basal ganglia subregion dedicated to learned vocalizations. These contained known targets of human FOXP2 and potential avian targets. We validated biological pathways not previously implicated in vocalization. Higher-order gene coexpression patterns, rather than expression levels, molecularly distinguish area X from the ventral striato-pallidum during singing. The previously unknown structure of singing-driven networks enables prioritization of molecular interactors that probably bear on human motor disorders, especially those affecting speech.     

Regeneration and transdetermination: new tricks from old cells

In this issue of Cell, Sustar and Schubiger (2005) address a longstanding question in regeneration biology: How is pluripotency achieved during regeneration? The authors have examined the cell cycle and growth characteristics of multipotent regenerating and transdetermining Drosophila cells and come up with some surprising findings.     

Action,time and the basal ganglia

The ability to control the speed of movement is compromised in neurological disorders involving the basal ganglia, a set of subcortical cerebral nuclei that receive prominent dopaminergic projections from the midbrain. For example, bradykinesia, slowness of movement, is a major symptom of Parkinson''s disease, whereas rapid tics are observed in patients with Tourette syndrome. Recent experimental work has also implicated dopamine (DA) and the basal ganglia in action timing. Here, I advance the hypothesis that the basal ganglia control the rate of change in kinaesthetic perceptual variables. In particular, the sensorimotor cortico-basal ganglia network implements a feedback circuit for the control of movement velocity. By modulating activity in this network, DA can change the gain of velocity reference signals. The lack of DA thus reduces the output of the velocity control system which specifies the rate of change in body configurations, slowing the transition from one body configuration to another.     

The role of the basal ganglia in habit formation

Many organisms, especially humans, are characterized by their capacity for intentional, goal-directed actions. However, similar behaviours often proceed automatically, as habitual responses to antecedent stimuli. How are goal-directed actions transformed into habitual responses? Recent work combining modern behavioural assays and neurobiological analysis of the basal ganglia has begun to yield insights into the neural basis of habit formation.     

CaMKII: new tricks for an old dog

Calcium/calmodulin-dependent protein kinase II (CaMKII) is a pivotal signaling molecule in both the brain and the heart. In this issue of Cell, Erickson et al. (2008) demonstrate a mechanism for CaMKII activation by reactive oxygen species that provides a direct link between kinase activation and cardiac dysfunction.