Timing and prediction the code from basal ganglia to thalamus

When is an inhibitory synapse not inhibitory? In this issue of Neuron, Person and Perkel demonstrate that thalamic neurons can translate extrinsic GABAergic input from the basal ganglia into highly precise patterns of sustained spiking in a circuit that is essential for vocal learning in songbirds. Postinhibitory rebound serves as a mechanism that preserves precise spike timing information, enabling reliable propagation of activity throughout this pathway. The results have broad implications for basic mechanisms of functional processing in both thalamus and basal ganglia and serve to increase our understanding of how acoustic units of vocal sounds are transformed into motor gestures during the sensitive period for song learning.     

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。     

The basal ganglia: learning new tricks and loving it

The field of basal ganglia research is exploding on every level - from discoveries at the molecular level to those based on human brain imaging. A remarkable series of new findings support the view that the basal ganglia are essential for some forms of learning-related plasticity. Other new findings are challenging some of the basic tenets of the field as it now stands. Combined with the new evidence on learning-related functions of the basal ganglia, these studies suggest that the basal ganglia are parts of a brain-wide set of adaptive neural systems promoting optimal motor and cognitive control.     

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.     

Dopamine-glutamate interactions in the basal ganglia

Summary In an attempt to formulate a working hypothesis of basal-ganglia functions, arguments are considered suggesting that the basal ganglia are involved in a process of response selection i.e. in the facilitation of wanted and in the suppression of unwanted behaviour. The meso-accumbal dopamine-system is considered to mediate natural and drug-induced reward and sensitization. The meso-striatal dopamine-system seems to fulfill similar funcions: It may mediate reinforcement which strengthens a given behaviour when elicited subsequently, but which is not experienced as reward or hedonia.Glutamate as the transmitter of the corticofugal projections to the basal ganglia nuclei and of the subthalamic neurons is critically involved in basal ganglia funcions and dysfunctions; for example Parkinson's disease can be considered to be a secondary hyperglutamatergic disease. Additionally, glutamate is an essential factor in the plasticity response of the basal-ganglia. However, opposite to previous suggestions, the NMDA-receptor blocker MK-801 does not prevent psychostimulant- nor morphine-induced day to day increase (sensitization) of locomotion. Also the day to day increase of haloperidol-induced catalepsy was not prevented by MK-801.     

The role of the striatum in aversive learning and aversive prediction errors

Neuroeconomic studies of decision making have emphasized reward learning as critical in the representation of value-driven choice behaviour. However, it is readily apparent that punishment and aversive learning are also significant factors in motivating decisions and actions. In this paper, we review the role of the striatum and amygdala in affective learning and the coding of aversive prediction errors (PEs). We present neuroimaging results showing aversive PE-related signals in the striatum in fear conditioning paradigms with both primary (shock) and secondary (monetary loss) reinforcers. These results and others point to the general role for the striatum in coding PEs across a broad range of learning paradigms and reinforcer types.     

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.     

Temporal prediction errors in a passive learning task activate human striatum

Functional MRI experiments in human subjects strongly suggest that the striatum participates in processing information about the predictability of rewarding stimuli. However, stimuli can be unpredictable in character (what stimulus arrives next), unpredictable in time (when the stimulus arrives), and unpredictable in amount (how much arrives). These variables have not been dissociated in previous imaging work in humans, thus conflating possible interpretations of the kinds of expectation errors driving the measured brain responses. Using a passive conditioning task and fMRI in human subjects, we show that positive and negative prediction errors in reward delivery time correlate with BOLD changes in human striatum, with the strongest activation lateralized to the left putamen. For the negative prediction error, the brain response was elicited by expectations only and not by stimuli presented directly; that is, we measured the brain response to nothing delivered (juice expected but not delivered) contrasted with nothing delivered (nothing expected).     

Motor functions of the basal ganglia

This session dealt with the structure and function of the basal ganglia and their role in motor control. The key issues discussed in the first four presentations concerned the pathophysiology of movement performance in parkinsonian patients and in animal models of this disease. Three papers were presented on neurochemically specified subsystems of the basal ganglia. Therapeutic aspects (stereoencephalotomy and chronic electrical stimulation of neural tissue) were discussed in the last two papers. A brief account is given on the highlights of each of these reports.     

PET imaging of the basal ganglia

The present chapter reviews PET imaging in basal ganglia disorders; Parkinson's disease is used as a model of these disorders because the neurochemical pathobiology of this disease is well known and great advances in the imaging area have been achieved. Other basal ganglia disorders including Tourette's syndrome, dystonia, Huntington's chorea and Wilson's disease are also dealt with. With PET and SPECT techniques, the whole integrative dopaminergic network of neurons can be studied, which plays an important role in differential diagnostics. Furthermore, pharmacological effects of medication can be visualized and the role of stereotaxic neurosurgery can be evaluated. Finally, functional imaging gives clues about the prognosis and rehabilitation aspects of the basal ganglia disorders.     

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.     

Histoenzymology of the developing human basal ganglia

Summary Oxidative and hydrolytic enzyme activities are present in the anlage of the human basal ganglia as early as the second month of embryonic life, and acetylcholinesterase activity appears during the sixth month of pre-natal life.Clinical Research Fellow of the Medical Research Council. Presently in the Department of Neurology, Indiana University, Medical School.     

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.     

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     

Metabotropic glutamate receptors in the basal ganglia motor circuit

In recent years there have been tremendous advances in our understanding of the circuitry of the basal ganglia and our ability to predict the behavioural effects of specific cellular changes in this circuit on voluntary movement. These advances, combined with a new understanding of the rich distribution and diverse physiological roles of metabotropic glutamate receptors in the basal ganglia, indicate that these receptors might have a key role in motor control and raise the exciting possibility that they might provide therapeutic targets for the treatment of Parkinson's disease and related disorders.     

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.