Considerations on the thalamostriatal system with some functional implications

The thalamostriatal projections are largely neglected in current reviews dealing with basal ganglia function. In the past few years, however, several studies have re-evaluated these projections and have postulated their implication in more complex tasks within the basal ganglia organization. In this review, we try to focus on the morphological and functional importance of this system in the basal ganglia of the rat, cat and monkey. Special attention is paid to the thalamus as an important place for interaction between the input and the output systems of the basal ganglia through the thalamostriatal projections. Thus, we stress on the overlapping thalamic territories between the thalamic projection of the output nuclei of the basal ganglia and the thalamostriatal neurons. Our experimental data support the existence of several thalamic feedback circuits within the basal ganglia functional design. Finally, some considerations are provided upon the functional significance of these thalamic feedback circuits in the overall organization of the basal ganglia in health and disease.     

Evidences for shared features in the organization of the basal ganglia in tetrapods: studies in amphibians.

In a series of recent studies, the organization of the basal ganglia of amphibians, more in particular their connectivity and chemoarchitecture, has been thoroughly analyzed. The pattern of organization found for the amphibian basal ganglia includes dorsal and ventral striatopallidal systems, reciprocal connections between the striatopallidal complex and structures derived from the diencephalic and mesencephalic parts of the basal plate (striatonigral and nigrostriatal projections), and descending pathways from the striatopallidal system to the midbrain tectum and the reticular formation of the brain stem. A comparative analysis of the organization of the basal ganglia in tetrapods strongly supports the notion that a primitive pattern was most likely present in ancestral tetrapods, and that many features can still be recognized in extant amphibians and amniotes.     

Evolution of the vertebrate motor system — from forebrain to spinal cord

A comparison of the vertebrate motor systems of the oldest group of now living vertebrates (lamprey) with that of mammals shows that there are striking similarities not only in the basic organization but also with regard to synaptic properties, transmitters and neuronal properties. The lamprey dorsal pallium (cortex) has a motor, a visual and a somatosensory area, and the basal ganglia, including the dopamine system, are organized in a virtually identical way in the lamprey and rodents. This also applies to the midbrain, brainstem and spinal cord. However, during evolution additional capabilities such as systems for the control of foreleg/arms, hands and fingers have evolved. The findings suggest that when the evolutionary lineages of mammals and lamprey became separate around 500 million years ago, the blueprint of the vertebrate motor system had already evolved.     

Receptor Autoradiography as a Tool for the Study of the Phylogeny of the Basal Ganglia

Abstract

Recent studies on the neurotransmitter organization of the basal ganglia and forebrain in lower vertebrates suggest that, in contrast to the old concepts of the phylogeny of the brain, there are many similarities between the chemical organization of the brain throughout evolution. By examining neurotransmitter receptors using in vitro autoradiography we have attempted to further our understanding of the evolution of the brain. Receptors enriched in different parts of the basal ganglia in mammals appear to be also enriched in the homologous areas in lower vertebrates. Thus, for example, dopamine and muscarinic receptors, but not serotonin-1A, are enriched in the paleostriatum augmentatum while GABA/benzo-diazepine receptors are enriched in the paleostriatum primitivum corresponding with their localization to the caudate-putamen and globus pallidus respectively. Our results support the concept of a more conservative evolution of the vertebrate brain and demonstrate the usefulness of receptor autoradiography in the understanding of brain evolution.     

The early topography of thalamocortical projections is shifted in Ebf1 and Dlx1/2 mutant mice

The prevailing model to explain the formation of topographic projections in the nervous system stipulates that this process is governed by information located within the projecting and targeted structures. In mammals, different thalamic nuclei establish highly ordered projections with specific neocortical domains and the mechanisms controlling the initial topography of these projections remain to be characterized. To address this issue, we examined Ebf1(-/-) embryos in which a subset of thalamic axons does not reach the neocortex. We show that the projections that do form between thalamic nuclei and neocortical domains have a shifted topography, in the absence of regionalization defects in the thalamus or neocortex. This shift is first detected inside the basal ganglia, a structure on the path of thalamic axons, and which develops abnormally in Ebf1(-/-) embryos. A similar shift in the topography of thalamocortical axons inside the basal ganglia and neocortex was observed in Dlx1/2(-/-) embryos, which also have an abnormal basal ganglia development. Furthermore, Dlx1 and Dlx2 are not expressed in the dorsal thalamus or in cortical projections neurons. Thus, our study shows that: (1) different thalamic nuclei do not establish projections independently of each other; (2) a shift in thalamocortical topography can occur in the absence of major regionalization defects in the dorsal thalamus and neocortex; and (3) the basal ganglia may contain decision points for thalamic axons' pathfinding and topographic organization. These observations suggest that the topography of thalamocortical projections is not strictly determined by cues located within the neocortex and may be regulated by the relative positioning of thalamic axons inside the basal ganglia.     

Structural basis of the striopallidum and the pedunculo-pontine tegmental nucleus participation in organization of adaptive behaviour

The method of retrograde axonal transport of peculiarities of the organization of afferent and efferent projection systems of separate substructures of the pedunculo-pontine tegmental nucleus and functionally various (motor and limbic) areas of the striopallidal structures allow to discuss the structural basis of carrying functionally diverse information and its integration in the basal ganglia system as well as in the tegmental region. The obtained morphological data prompts understanding of the morpho-functional basis of interaction of the structures under study and their participation in adaptive behaviour.     

Specific and nonspecific cortical-subcortical mechanisms of behavior

The paper presents data on comparative morphological study of afferent connections between the cat, dog, monkey brain basal ganglia with structures of the "motor" and "limbic" systems, neurophysiological data on specifics of involvement of the pre-frontal cortex, amygdala, caudate nucleus and thalamus in the processes of learning, perception and assessment of the stimuli significance, formation of short- and long-term memory's programs, decision making, programming the actions and assessment of the actions being performed, experimental data on the role of glutamatergic, dopaminergic, cholinergic, GABA-ergic systems of the cortex and a number of subcortical structures in the mechanisms of formation and implementation of the food and defence reflexes.     

The functional anatomy of the basal ganglia of birds.

To study how the basal ganglia can control movement in birds, we have reinvestigated the connections of the pigeon dorsal pallidum. Our results indicate that avian basal ganglia appear to control movement through major projections to several premotor pretectal and tegmental centres which innervate the tectum, and through a minor projection to a possible motor thalamic centre which innervates the Wulst. For such control, separate striatopallidal output circuits appear to exist in birds that are remarkably similar to those described in mammals, suggesting that avian and mammalian basal ganglia may control movement through similar mechanisms, and that the morphological substrate for such control evolved earlier than previously thought.     

Motor actions of cannabinoids in the basal ganglia output nuclei.

The levels of CB1 cannabinoid receptors in the basal ganglia are the highest in the brain, comparable to the levels of dopamine receptors, a major transmitter in the basal ganglia. This localization of receptors is consistent with the profound effects on motor function exerted by cannabinoids. The output nuclei of the basal ganglia, the globus pallidus (GP) and substantia nigra reticulata (SNr), apparently lack intrinsic cannabinoid receptors. Rather, the receptors are located on afferent terminals, the striatum being the major source. Cannabinoids blocked the inhibitory action of the striatal input in the SNr. Furthermore, cannabinoids blocked the excitatory effect of stimulation of the subthalamic input to the SNr revealing, along with data from in situ hybridization studies, that this input is another likely source of cannabinoid receptors to the SNr. Similar actions of cannabinoids were observed in the GP. Behavioral studies further revealed that the action of cannabinoids differs depending upon which input to the output nuclei of the basal ganglia is active. The inhibitory striatal input is quiescent and the cannabinoid action is observable only upon stimulation of the striatum, while the noticeable effect of cannabinoids under basal conditions would be on the tonically active subthalamic input. These data suggest that the recently discovered endogenous cannabinergic system exerts a major modulatory action in the basal ganglia by its ability to block both the major excitatory and inhibitory inputs to the SNr and GP.     

Central nervous system of Chaetoderma japonicum (Caudofoveata, Aplacophora): implications for diversified ganglionic plans in early molluscan evolution

The organization of the central nervous system of an "aplacophoran" mollusc, Chaetoderma japonicum, is described as a means to understand a primitive condition in highly diversified molluscan animals. This histological and immunocytochemical study revealed that C. japonicum still retains a conservative molluscan tetra-neural plan similar to those of neomenioids, polyplacophorans, and tryblidiids. However, the ventral and lateral nerve cords of C. japonicum are obviously ganglionated to various degrees, and the cerebral cord-like ganglia display a lobular structure. The putative chemosensory networks are developed, being composed of sensory cells of the oral shield, eight precerebral ganglia, and eight neuropil compartments that form distinct masses of neurites. In the cerebral cord-like ganglia, three anterior, posterior, and dorsal lobes are distinguished with well-fasciculated tracts in their neuropils. Most neuronal somata are uniform in size, and no small globuli-like cell clusters are found; however, localized serotonin-like immunoreactivity and acetylated tubulin-containing tracts suggest the presence of functional subdivisions. These complicated morphological features may be adaptive structures related to the specialized foraminiferan food in muddy bottoms. Based on a comparative scheme in basal molluscan groups, we characterize an independent evolutionary process for the unique characters of the central nervous systems of chaetoderms.     

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.     

A neurophysiologic model for aggressive behavior in the cat

A neurophysiologic model for aggressive behavior in the cat is proposed. Stimulus-bound and seizure-bound aggression was evaluated in relation to limbic and basal ganglia induced seizures (after-discharges). Electrically induced limbic and basal ganglia after-discharges were used because they are known to implicate septohypothalamic sites from which aggression can be elicited by direct stimulation. The occurrence of behavioral aggression is correlated with the discharge characteristics of a single discharging system and with two interacting discharging systems. Aggression is composed of autonomic and somato-motor components which poses relatively low and high thresholds, respectively, for their activation. Aggression occurring during a combined septum and amygdala discharge was more intense and prolonged than with a septum discharge alone. Participation of a slow frequency discharging basal ganglia system activated seizure-bound aggression in an otherwise nonaggressive limbic seizure. The limbic and basal ganglia stimulations and after-discharges lowered the excitability threshold of the aggression system and made it more vulnerable to being activated by external stimuli, such as visual and auditory stimuli. These observations are reminiscent of patients with aggressive behavior associated with psychomotor seizures.     

Pathophysiology of levodopa-induced dyskinesia: potential for new therapies

Involuntary movements--or dyskinesias--are a debilitating complication of levodopa therapy for Parkinson's disease, and is experienced in most patients. Despite the importance of this problem, little was known about the cause of dyskinesia until recently; however, this situation has changed significantly in the past few years. Our increased understanding of levodopa-induced dyskinesia is not only valuable for improving patient care, but also in providing us with new insights into the functional organization of the basal ganglia and motor systems.     

Two-phase model of the basal ganglia: implications for discontinuous control of the motor system

In this article, I point out that simple one-phase models of the role of the basal ganglia in action selection have a problem. Furthermore, I suggest a solution with major implications for the organization of the action-selection and motor systems. In current models, the striatum evaluates multiple potential actions by adding biases based on previous conditioning. These biases may arise in both the direct (bias for) and indirect (bias against) pathways. Together, these biases influence which action is ultimately chosen. For efficient conditioning to occur, a positive outcome must selectively strengthen the striatal bias for the chosen action (via a dopaminergic mechanism). This is problematic, however, because all potential action choices have influenced firing patterns in striatal cells during the selection process; it is therefore unclear how the synapses that represent the chosen plan could be selectively strengthened. I suggest a simple solution in which the striatum has two functional phases. In the first phase, the basal ganglia provide biases for multiple potential actions (using both the direct and indirect pathways), leading to the choice of a single action in the cortex. In the second phase, an efference copy of the chosen action is sent to the striatum, where it contributes to the establishment of the eligibility trace for that action. This trace, when acted on by subsequent dopaminergic reinforcement, leads to specific strengthening of the bias only for the chosen action. Consistent with this model, recordings show post-choice imposition onto the striatum of signals corresponding to the chosen action. The existence of dual phases of basal ganglia function implies that decisions about action choice are sent to the motor system in a discontinuous manner. This would not be problematic if the motor system also operated discontinuously. I will review evidence suggesting that this is the case, notably that action is organized by approximately 10 Hz oscillations.     

The Striatum: Where Skills and Habits Meet

After more than a century of work concentrating on the motor functions of the basal ganglia, new ideas have emerged, suggesting that the basal ganglia also have major functions in relation to learning habits and acquiring motor skills. We review the evidence supporting the role of the striatum in optimizing behavior by refining action selection and in shaping habits and skills as a modulator of motor repertoires. These findings challenge the notion that striatal learning processes are limited to the motor domain. The learning mechanisms supported by striatal circuitry generalize to other domains, including cognitive skills and emotion-related patterns of action.The nuclei and interconnections of the basal ganglia are widely recognized for modulating motor behavior. Whether measured at the neuronal or regional level, the activities of neurons in the basal ganglia correlate with many movement parameters, particularly those that influence the vigor of an action, such as force and velocity. Pathology within different basal ganglia circuits predictably leads to either hypokinetic or hyperkinetic movement disorders. In parallel, however, the basal ganglia, and especially the striatum, are now widely recognized as being engaged in activity related to learning. Interactions between the dopamine-containing neurons of the midbrain and their targets in the striatum are critical to this function. A fundamental question is how these two capacities—(motor behavior and reinforcement-based learning)—relate to each other and what role the striatum and other basal ganglia nuclei have in forming new behavioral repertoires. Here, we consider relevant physiological properties of the striatum by contrasting two common forms of adaptation found in all mammals: the acquisition of behavioral habits and physical skills.Without resorting to technical definitions, we all have an intuition of what habits and skills are. Tying one’s shoes after putting them on is something we consider a habit—part of a behavioral routine. The capacity to tie the laces properly is a skill. Habits and skills have many common features. Habits are consistent behaviors triggered by appropriate events (typically, but not always, external stimuli) occurring within particular contexts. Physical skills are changes in a physical repertoire: new combinations of movements that lead to new capacities for goal-directed action. Both habits and skills can leverage reward-based learning, particularly during their initial acquisition. In either instance, after sufficient experience, the need for reward becomes lower and lower. With sufficient practice, both lead to “automaticity” and a resilience against competing actions that might lead to unlearning.     

Dichotomous organization of the external globus pallidus

Different striatal projection neurons are the origin of?a?dual organization essential for basal ganglia function. We have defined an analogous division of labor in the external globus pallidus (GPe) of Parkinsonian rats, showing that the distinct temporal activities of two populations of GPe neuron in?vivo are?underpinned by distinct molecular profiles and axonal connectivities. A first population of prototypic GABAergic GPe neurons fire antiphase to subthalamic nucleus (STN) neurons, often express parvalbumin, and target downstream basal ganglia nuclei, including STN. In contrast, a second population (arkypallidal neurons) fire in-phase with STN neurons, express preproenkephalin, and only innervate the striatum. This novel cell type provides the largest extrinsic GABAergic innervation of striatum, targeting both projection neurons and interneurons. We conclude that GPe exhibits several core components of?a dichotomous organization as fundamental as?that in striatum. Thus, two populations of GPe neuron?together orchestrate activities across all basal ganglia nuclei in a cell-type-specific manner.     

Estimating Material and Energy Flows in Life Cycle Inventory with Statistical Models

Data (un)availability and uncertainty are recurring problems in life cycle assessment, and particularly inventory analysis. Advances in life cycle inventory have focused on the propagation and management of uncertainty, but this article addresses the question of how to account for unavailable data and corresponding uncertainty. Large and complicated systems often lack complete data due to confidential practices or the efforts required in the data collection process. Electricity production with multiple processes generating a single product is a classic example. Instead of the conventional process‐based models to estimate missing data, the approach developed in this article divides systems based on functionally equivalent objects. Each one of these objects is then described in terms of characteristic variables, such as power capacity. Kriging, a flexible statistical estimator, allows for the estimation of unknown material and energy flows based on the objects’ characteristic variables. Both univariate and multivariate kriging are tested and compared to regression analysis. It is found that kriging performs better than linear regression, according to the mean absolute error criterion. Multivariate kriging provides an even more accurate joint estimation method to bridge data gaps scattered across inventories and when observable values of material and energy flows differ from one object to the next. Parameters of the underlying models are interpreted in terms of data uncertainty.     

Analysis of structural basis of information processing in basal ganglia: spatial organization of the thalamo-striatal projections in the dog brain

Distribution of neurones labelled in a retrograde way, studied in functionally different dog's thalamic nuclei, elucidated anatomical aspects of functional heterogeneity of the basal ganglia and of integrative information processing, as well as the organization of adaptive behaviour mechanisms.     

Metabolic changes in the basal ganglia of patients with Huntington's disease: an in situ hybridization study of cytochrome oxidase subunit I mRNA

On the basis of the functional model of the basal ganglia developed in the 1980s and the neuropathological findings in Huntington's disease (HD), changes in the neuronal activity of the basal ganglia have previously been proposed to explain the abnormal movements observed in this pathology. In particular, it has been stated that the neurodegenerative process affecting the basal ganglia in the disease should provoke a hypoactivity in the internal segment of the pallidum (GPi) that could explain choreic movements observed in the disease. To test this functional hypothesis, we performed an in situ hybridization study on control and HD brains postmortem, taking cytochrome oxidase subunit I (COI) mRNAs expression as index of neuronal activity. As most of the HD patients studied were under chronic neuroleptic (NL) treatment, we also studied the brains of non-HD patients under chronic NL treatment. Our results show that in HD brain the number of neurons expressing COI mRNA tends to be lower in the striatum, GPe and GPi, suggesting a severe involvement of these structures during the neurodegenerative process. Moreover, COI mRNA level of expression was markedly reduced within neurons of the putamen and GPe. Surprisingly, COI mRNA expression was not modified in the GPi in HD brains compared with controls. This paradoxical result in the GPi may be explained by the antagonistic effect of GPe hypoactivity and the degenerative process involving neurons of GPi. Our results indicate that the functional modifications, and consequently the pathophysiology of abnormal movements, observed in HD basal ganglia are more complex than expected from the currently accepted model of the basal ganglia organization.     

A neural model of basal ganglia-thalamocortical relations in normal and parkinsonian movement

 Anatomical, neurophysiological, and neurochemical evidence supports the notion of parallel basal ganglia–thalamocortical motor systems. We developed a neural network model for the functioning of these systems during normal and parkinsonian movement. Parkinson’s disease (PD), which results predominantly from nigrostriatal pathway damage, is used as a window to examine basal ganglia function. Simulations of dopamine depletion produce motor impairments consistent with motor deficits observed in PD that suggest the basal ganglia play a role in motor initiation and execution, and sequencing of motor programs. Stereotaxic lesions in the model’s globus pallidus and subthalamic nucleus suggest that these lesions, although reducing some PD symptoms, may constrain the repertoire of available movements. It is proposed that paradoxical observations of basal ganglia responses reported in the literature may result from regional functional neuronal specialization, and the non-uniform distributions of neurochemicals in the basal ganglia. It is hypothesized that dopamine depletion produces smaller-than-normal pallidothalamic gating signals that prevent rescalability of these signals to control variable movement speed, and that in PD can produce smaller-than-normal movement amplitudes. Received: 1 September 1994/Accepted in revised form: 16 May 1995