Intracerebral displacement of basal ganglia following septal cannulation.

The effects of septal cannulation on the displacement of basal ganglia form the basis of the present communication. In experimental rats, in which a cannula is chronically implanted for 30 days between the medial and lateral septal nuclei by stereotaxic procedures, considerable shift of the basal ganglion is always observed on the operated side. The displacement takes place along the long axis of the ganglion either rostrally or caudally. Besides gross asymmetry in their relative sizes, no histological differences are observed between the ganglia of the two sides. Control animals, in which the cannula is withdrawn immediately after the septal lesion, manifest similar, but less pronounced movements of the basal ganglia. The probable underlying mechanisms for such intracerebral shifts are discussed and the role of indirect mechanical forces is outlined. The extraordinary degree of plasticity of the subcortical nuclear masses in terms of mobility is also emphasized.     

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.     

Effects on hypothalamus when CPG is fed back to basal ganglia based on KIV model

The KIV model approximates the operation of the basic vertebrate forebrain together with the basal ganglia and motor systems. In KIV model, the hypothalamus and the basal ganglia which are two important parts in the midline forebrain are closely associated with the locomotion. The CPG model with time delay is established in this paper and the stability of this CPG model is discussed. The CPG output is treated as the proprioception and fed back to the basal ganglia. We focus on the effects on the hypothalamus and the basal ganglia when the time delay parameter a_d, the CPG amplitude parameter e and the CPG frequency parameter T_r are changed. Through analysis, we find that there exists optimum value of the parameters a_d or T_r which can make the synchronization of the hypothalamus optimum when the CPG is added into the basal ganglia. The results could have important implications for biological processes which are about interaction between the neural network and the CPG.     

The basal ganglia-circa 1982. A review and commentary

Our review has shown that recent studies with the new anterograde and retrograde axon transport methods have confirmed and extended our knowledge of the projection of the basal ganglia and clarified their sites of origin. They have thrown new light on certain topographic connectional relationships and revealed several new reciprocal connections between constituent nuclei of the basal ganglia. Similarly, attention has been drawn to the fact that there have also been many new histochemical techniques introduced in recent years that are now providing regional biochemical overlays for connectional maps of the central nervous system, especially regions in, or interconnecting with, the basal ganglia. However, although these new morphological biochemical maps are very complex and technically highly advanced, our understanding of the function controlled by the basal ganglia still remains primitive. The reader who is interested in some new ideas of the functional aspects of the basal ganglia is directed to Nauta's [88] proposed conceptual reorganization of the basal ganglia telencephalon and to Marsden's [72] more clinically orientated appraisal of the unsolved mysteries of the basal ganglia participation in the control of movement.     

Comprehensive in vivo mapping of the human basal ganglia and thalamic connectome in individuals using 7T MRI

Basal ganglia circuits are affected in neurological disorders such as Parkinson's disease (PD), essential tremor, dystonia and Tourette syndrome. Understanding the structural and functional connectivity of these circuits is critical for elucidating the mechanisms of the movement and neuropsychiatric disorders, and is vital for developing new therapeutic strategies such as deep brain stimulation (DBS). Knowledge about the connectivity of the human basal ganglia and thalamus has rapidly evolved over recent years through non-invasive imaging techniques, but has remained incomplete because of insufficient resolution and sensitivity of these techniques. Here, we present an imaging and computational protocol designed to generate a comprehensive in vivo and subject-specific, three-dimensional model of the structure and connections of the human basal ganglia. High-resolution structural and functional magnetic resonance images were acquired with a 7-Tesla magnet. Capitalizing on the enhanced signal-to-noise ratio (SNR) and enriched contrast obtained at high-field MRI, detailed structural and connectivity representations of the human basal ganglia and thalamus were achieved. This unique combination of multiple imaging modalities enabled the in-vivo visualization of the individual human basal ganglia and thalamic nuclei, the reconstruction of seven white-matter pathways and their connectivity probability that, to date, have only been reported in animal studies, histologically, or group-averaged MRI population studies. Also described are subject-specific parcellations of the basal ganglia and thalamus into sub-territories based on their distinct connectivity patterns. These anatomical connectivity findings are supported by functional connectivity data derived from resting-state functional MRI (R-fMRI). This work demonstrates new capabilities for studying basal ganglia circuitry, and opens new avenues of investigation into the movement and neuropsychiatric disorders, in individual human subjects.     

Morphological analysis of information processing in basal ganglia of mammals

The article reviews published and own data on special features of organization of afferent cortical and infracortical correctional systems of the total striopallidaric nuclear complex in various species of mammals. The article focuses on analysis of organization of these flows in a dog being a classical object of behavioural experiments and a rare object of neuromorphological studies. It was discovered that the general trend towards segregated and converged flows of functionally different information at the level of striopallidum is retained in all tested mammals, being an evidence of the fundamental nature of the discussed principles of organization of the projection systems of basal ganglia. The reviewed morphological data confirm reliability of the presented concept of basal ganglia functioning.     

Anatomical funneling, sparse connectivity and redundancy reduction in the neural networks of the basal ganglia

The major anatomical characteristics of the main axis of the basal ganglia are: (1) Numerical reduction in the number of neurons across layers of the feed-forward network, (2) lateral inhibitory connections within the layers, and (3) neuro-modulatory effects of dopamine and acetylcholine, both on the basal ganglia neurons and on the efficacy of information transmission along the basal ganglia axis. We recorded the simultaneous activity of neurons in the output stages of the basal ganglia as well as the activity of dopaminergic and cholinergic neurons during the performance of a probability decision-making task. We found that the functional messages of the cholinergic and dopaminergic neurons differ, and that the cholinergic message is less specific than that of the dopaminergic neurons. The output stage of the basal ganglia showed uncorrelated neuronal activity. We conclude that despite the huge numerical reduction from the cortex to the output nuclei of the basal ganglia, the activity of these nuclei represents an optimally compressed (uncorrelated) version of distinctive features of cortical information.     

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.     

Possible mechanisms of firing patterns reorganization of the neurons of the output nuclei basal ganglia

Previously proposed unitary modification rules and known experimental data were used for understanding possible mechanisms of reorganization of firing patterns of neurons in the output basal ganglia nuclei. According to the suggested mechanism, a switch from regular-spiking to bursting activity evoked by systemic inactivation of N-methyl-d-aspartate (NMDA) receptors or dopaminic receptors mainly depends on modifications of cortico-striatal synapses whereas the opposite effect of inactivation of the same receptors directly on the output basal ganglia cells is less effective. We hypothesized that some of the output basal ganglia nuclei neurons which can generate bursting discharges due to inactivation of NMDA and dopaminic receptors are glutamatergic or cholinergic cells.     

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.     

The role of medial temporal lobe structures in implicit learning: an event-related FMRI study

The medial temporal lobe (MTL) has been associated with declarative learning of flexible relational rules and the basal ganglia with implicit learning of stimulus-response mappings. It remains an open question of whether MTL or basal ganglia are involved when learning flexible relational contingencies without awareness. We studied learning of an explicit stimulus-response association with fMRI. Embedded in this explicit task was a hidden structure that was learnt implicitly. Implicit learning of the sequential regularities of the "hidden rule" activated the ventral perirhinal cortex, within the MTL, whereas learning the fixed stimulus-response associations activated the basal ganglia, indicating that the function of the MTL and the basal ganglia depends on the learned material and not necessarily on the participants' awareness.     

MRI evaluation of basal ganglia ferritin iron and neurotoxicity in Alzheimer's and Huntingon's disease.

BACKGROUND: The basal ganglia contain the highest levels of iron in the brain and post-mortem studies indicate a disruption of iron metabolism in the basal ganglia of patients with neurodegenerative disorders such as Alzheimer's disease (AD) and Huntington's disease (HD). Iron can catalyze free radical reactions and may contribute to oxidative damage observed in AD and HD brain. Magnetic resonance imaging (MRI) can quantify transverse relaxation rates, which can be used to quantify tissue iron stores as well as evaluate increases in MR-visible water (an indicator of tissue damage). METHODS: A magnetic resonance imaging (MRI) method termed the field dependent relaxation rate increase (FDRI) was employed which quantifies the iron content of ferritin molecules (ferritin iron) with specificity through the combined use of high and low field-strength MRI instruments. Three basal ganglia structures (caudate, putamen and globus pallidus) and one comparison region (frontal lobe white matter) were evaluated. Thirty-one patients with AD and a group of 68 older control subjects, and 11 patients with HD and a group of 27 adult controls participated (4 subjects overlap between AD and HD controls). RESULTS: Compared to their respective normal control groups, increases in basal ganglia FDRI levels were seen in both AD and HD. FDRI levels were significantly increased in the caudate (p = 0.007) and putamen (p = 0.008) of patients with AD with a trend toward an increase in the globus pallidus (p = 0.13). In the patients with HD, all three basal ganglia regions showed highly significant FDRI increases (p<0.001) and the magnitude of the increases were 2 to 3 times larger than those observed in AD versus control group comparison. For both HD andAD subjects, the basal ganglia FDRI increase was not a generalized phenomenon, as frontal lobe white matter FDRI levels were decreased in HD (p = 0.015) and remained unchanged in AD. Significant low field relaxation rate decreases (suggestive of increased MR-visible water and indicative of tissue damage) were seen in the frontal lobe white matter of both HD and AD but only the HD basal ganglia showed such decreases. CONCLUSIONS: The data suggest that basal ganglia ferritin iron is increased in HD and AD. Furthermore, the increased iron levels do not appear to be a byproduct of the illness itself since they seem to be present at the onset of the diseases, and thus may be considered a putative risk factor. Published post-mortem studies suggest that the increase in basal ganglia ferritin iron may occur through different mechanisms in HD and AD. Consistent with the known severe basal ganglia damage, only HD basal ganglia demonstrated significant decreases in low field relaxation rates. MRI can be used to dissect differences in tissue characteristics, such as ferritin iron and MR-visible water, and thus could help clarify neuropathologic processes in vivo. Interventions aimed at decreasing brain iron levels, as well as reducing the oxidative stress associated with increased iron levels, may offer novel ways to delay the rate of progression and possibly defer the onset of AD and HD.     

The endocannabinoid system: a physiological perspective on its role in psychomotor control

The discovery of cannabinoid receptors has led to the identification of two natural activators for these receptors, anandamide and 2-arachidonoylglycerol, and to the elucidation of their biochemical pathways of formation and inactivation. Although the physiological significance of the endogenous cannabinoid system is still poorly understood, important information is becoming available on the possible functional roles of this system in the basal ganglia, a forebrain region that is involved in the control of sensorimotor and motivational aspects of behavior. These discoveries - which are going to enrich the way in which we look at basal ganglia functions - are summarized in this mini-review. The role of the endocannabinoids as modulators of psychomotor behaviors and the potential therapeutic perspectives deriving from the pharmacological manipulation of the endogenous cannabinoid system are also discussed.     

Cholinergic and catecholaminergic neurons relay striatal information to the optic tectum in amphibians.

In the amphibians Rana perezi and Xenopus laevis, the involvement of cholinergic and catecholaminergic neurons in the relay of basal ganglia inputs to the tectum was investigated. Tract-tracing experiments, in which anterograde tracers were applied to the basal ganglia and retrograde tracers to the optic tectum, were combined with immunohistochemistry for choline acetyltransferase and tyrosine hydroxylase. The results of these experiments suggest that dopaminergic neurons of the suprachiasmatic nucleus and pretectal region, noradrenergic cells of the locus coeruleus and the cholinergic neurons of the pedunculopontine and laterodorsal tegmental nuclei mediate at least part of the basal ganglia input to the tectum in anurans.     

Factors regulating the activity of striatal neurons: New perspectives fromin situ hybridization histochemistry

1. The basal ganglia contain a variety of putative peptide neurotransmitters. In situ hybridization allows changes in the levels of the mRNAs encoding these neuropeptides to be assessed at the cellular level of resolution. 2. Alterations in the activity of pathways within the basal ganglia of the rat produce distinct effects on the different neuropeptide mRNAs. 3. The evidence, where available, suggests that mRNA levels provide an index of peptide turnover. 4. This approach has consequently revealed much new information on the regulation of neuronal activity in the basal ganglia.     

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.     

Complementary 'bottom-up' and 'top-down' approaches to basal ganglia function

Recently, two quite different approaches exemplifying 'bottom-up' and 'top-down' philosophies have shed new light on basal ganglia function. In vitro work using organotypic co-cultures has implicated the subthalamic nucleus (STN) and the external segment of the globus pallidus (GP(e)) as pacemakers for low-frequency bursting that is reminiscent of the activity produced in Parkinsonian tremor. A circuit essential for avian song learning has been identified as part of the basal ganglia with surprisingly well conserved cellular details; investigation of this system may help to address general issues of basal ganglia function.     

Effect of 6-Hydroxydopamine Lesions of the Medial Prefrontal Cortex on Neurotransmitter Systems in Subcortical Sites in the Rat

The effect of lesions of the catecholamine nerve terminals in the medial prefrontal cortex of the rat on neurotransmitter mechanisms within the basal ganglia has been investigated. Bilateral 6-hydroxydopamine lesions were stereotaxically placed in the dopamine-rich (DA) area of th frontal cortex. Animals were pretreated with desmethylimipramine to block the uptake of neurotoxin into noradrenergic (NA) terminals and to make it more selective for DA terminals. The lesion produced a selective reduction of both NA and DA from the medial prefrontal cortex, a result related to falls in tyrosine hydroxylase activity at this site. Lesioned animals showed enhanced DA turnover and utilisation in striatal and limbic regions. There was no change in subcortical tyrosine hydroxylase activity. In addition there were significant falls in other putative neurotransmitters within basal sites, including 5-hydroxytryptamine and GABA. Decreased activity of the neurotransmitter-synthesizing enzyme glutamate decarboxylase and choline acetyltransferase was also recorded in certain regions of the basal ganglia. The results suggest that frontal cortical catecholamine systems may serve to regulate various neurotransmitter mechanisms in the basal ganglia.     

Input to the lateral habenula from the basal ganglia is excitatory, aversive, and suppressed by serotonin

The lateral habenula (LHb) has recently been identified as a key regulator of the reward system by driving inhibition onto dopaminergic neurons. However, the nature and potential modulation of the major input to the LHb originating from the basal ganglia are poorly understood. Although the output of the basal ganglia is thought to be primarily inhibitory, here we show that transmission from the basal ganglia to the LHb is excitatory, glutamatergic, and suppressed by serotonin. Behaviorally, activation of this pathway is aversive, consistent with its role as an "antireward" signal. Our demonstration of an excitatory projection from the basal ganglia to the LHb explains how LHb-projecting basal ganglia neurons can have similar encoding properties as LHb neurons themselves. Our results also provide a link between antireward excitatory synapses and serotonin,?a neuromodulator implicated in depression.