Functional Circuitry of the Basal Ganglia

Nambu, Atsushi

doi:10.1007/978-3-319-08476-3_1

Cited by 6 publications

(4 citation statements)

References 48 publications

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“…The GPi/SNr, which are considered to be a single structure divided by the internal capsule, are the basal ganglia output station. They further integrate inputs from other basal ganglia components and send their projections predominantly to the thalamus, but also to brainstem nuclei (Nambu 2015). The GPe connects these input and output stations, and the SNc modulates the network (Bar-Gad and Bergman 2001; Rivlin-Etzion et al 2006).…”

Section: Anatomy and Pathophysiologymentioning

confidence: 99%

Putting the Pieces Together in Gilles de la Tourette Syndrome: Exploring the Link Between Clinical Observations and the Biological Basis of Dysfunction

2016

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Gilles de la Tourette syndrome is a complex, idiopathic neuropsychiatric disorder whose pathophysiological mechanisms have yet to be elucidated. It is phenotypically heterogeneous and manifests more often than not with both motor and behavioral impairment, although tics are its clinical hallmark. Tics themselves present with a complex profile as they characteristically wax and wane and are often preceded by premonitory somatosensory sensations to which it is said a tic is the response. Highly comorbid with obsessive–compulsive disorder and attention deficit-hyperactivity disorder, it is purported to be an epigenetic, neurodevelopmental spectrum disorder with a complex genetic profile. It has a childhood onset, occurs disproportionately in males, and shows spontaneous symptomatic attenuation by adulthood in the majority of those afflicted. Although not fully understood, its neurobiological basis is linked to dysfunction in the cortico-basal ganglia–thalamo–cortical network. Treatment modalities for Tourette syndrome include behavioral, pharmacological and surgical interventions, but there is presently no cure for the disorder. For those severely affected, deep brain stimulation (DBS) has recently become a viable therapeutic option. A key factor to attaining optimal results from this surgery is target selection, a topic still under debate due to the complex clinical profile presented by GTS patients. Depending on its phenotypic expression and the most problematic aspect of the disorder for the individual, one of three brain regions is most commonly chosen for stimulation: the thalamus, globus pallidus, or nucleus accumbens. Neurophysiological analyses of intra- and post-operative human electrophysiological recordings from clinical DBS studies suggest a link between tic behavior and activity in both the thalamus and globus pallidus. In particular, chronic recordings from the thalamus have shown a correlation between symptomatology and (1) spectral activity in gamma band power and (2) theta/gamma cross frequency coherence. These results suggest gamma oscillations and theta/gamma cross correlation dynamics may serve as biomarkers for dysfunction. While acute and chronic recordings from human subjects undergoing DBS have provided better insight into tic genesis and the neuropathophysiological mechanisms underlying Tourette syndrome, these studies are still sparse and the field would greatly benefit from further investigations. This review reports data and discoveries of scientific and clinical relevance from a wide variety of methods and provides up-to-date information about our current understanding of the pathomechanisms underlying Tourette syndrome. It gives a comprehensive overview of the current state of knowledge and addresses open questions in the field.

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Section: Anatomy and Pathophysiologymentioning

confidence: 99%

Putting the Pieces Together in Gilles de la Tourette Syndrome: Exploring the Link Between Clinical Observations and the Biological Basis of Dysfunction

2016

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“…They are primarily involved in the complex control of voluntary movement and mood. Core structures of the basal ganglia include; the striatum (caudate nucleus, CN and putamen, PD), the globus pallidus (both externus, GPe, and internus, GPi), the substantia nigra, which is divided into two segments, the substantia nigra pars compacta (SNc) and substantia nigra pars reticulata (SNr), and also includes the subthalamic nucleus (STN) (Albin, Young, & Penney, ; Nambu, ; Yelnik, ). The STN is unique in the basal ganglia as it is the only glutamatergic nucleus within the circuitry (Smith & Parent, ).…”

Section: Introductionmentioning

confidence: 99%

GABA_A and GABA_B receptor subunit localization on neurochemically identified neurons of the human subthalamic nucleus

Song

Faull

et al. 2017

J of Comparative Neurology

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The subthalamic nucleus (STN) is a critical excitatory signaling center within the basal ganglia circuitry. The activity of subthalamic neurons is tightly controlled by upstream inhibitory signaling centers in the basal ganglia. In this study, we used immunohistochemical techniques to firstly, visualize and quantify the STN neurochemical organization based on neuronal markers including parvalbumin (PV), calretinin (CR), SMI-32, and GAD . Secondly, we characterized the detailed regional, cellular and subcellular expression of GABA (α , α , α , β , and γ ) and GABA (R1 and R2) receptor subunits within the normal human STN. Overall, we found seven neurochemically distinct populations of principal neurons in the human STN. The three main populations detected were: (a) triple-labeled PV /CR /SMI32 ; (b) double-labeled PV /CR ; and (c) single-labeled CR neurons. Subthalamic principal neurons were found to express GABA receptor subunits α , α , β , γ , and GABA receptor subunits R1 and R2. However, no expression of GABA receptor α subunit was detected. We also found a trend of increasing regional staining intensity for all positive GABA receptor subunits from the dorsolateral pole to ventromedial extremities. The GAD interneurons showed relatively low expression of GABA receptor subunits. These results provide the morphological basis of GABAergic transmission within the normal human subthalamic nucleus and evidence of GABA innervation through both GABA and GABA receptors on subthalamic principal neurons.

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“…The full set of equations related to the Izhikevich spiking neuron model are described in Appendix A and Table A.I (Supplementary Materials). The input from the cortex to STN, also known as the hyper-direct pathway (Nambu, 2015 ), and the GABAergic projection from GPe to GPi were not included in the model as the functional significance of these connections is not fully understood.…”

Section: Methodsmentioning

confidence: 99%

Probing the Role of Medication, DBS Electrode Position, and Antidromic Activation on Impulsivity Using a Computational Model of Basal Ganglia

Mandali

Chakravarthy

2016

Front. Hum. Neurosci.

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Everyday, we encounter situations where available choices are nearly equally rewarding (high conflict) calling for some tough decision making. Experimental recordings showed that the activity of Sub Thalamic Nucleus (STN) increases during such situations providing the extra time needed to make the right decision, teasing apart the most rewarding choice from the runner up closely trailing behind. This prolonged deliberation necessary for decision making under high conflict was absent in Parkinson's disease (PD) patients who underwent Deep Brain Stimulation (DBS) surgery of STN. In an attempt to understand the underlying cause of such adverse response, we built a 2D spiking network model (50 × 50 lattice) of Basal ganglia incorporating the key nuclei. Using the model we studied the Probabilistic learning task (PLT) in untreated, treated (L-Dopa and Dopamine Agonist) and STN-DBS PD conditions. Based on the experimental observation that dopaminergic activity is analogous to temporal difference (TD) and induces cortico-striatal plasticity, we introduced learning in the cortico-striatal weights. The results show that healthy and untreated conditions of PD model were able to more or less equally select (avoid) the rewarding (punitive) choice, a behavior that was absent in treated PD condition. The time taken to select a choice in high conflict trials was high in normal condition, which is in agreement with experimental results. The treated PD (Dopamine Agonist) patients made impulsive decisions (small reaction time) which in turn led to poor performance. The underlying cause of the observed impulsivity in DBS patients was studied in the model by (1) varying the electrode position within STN, (2) causing antidromic activation of GPe neurons. The effect of electrode position on reaction time was analyzed by studying the activity of STN neurons where, a decrease in STN neural activity was observed for certain electrode positions. We also observed that a higher antidromic activation of GPe neurons does not impact the learning ability but decreases reaction time as reported in DBS patients. These results suggest a probable role of electrode and antidromic activation in modulating the STN activity and eventually affecting the patient's performance on PLT.

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Functional Circuitry of the Basal Ganglia

Cited by 6 publications

References 48 publications

Putting the Pieces Together in Gilles de la Tourette Syndrome: Exploring the Link Between Clinical Observations and the Biological Basis of Dysfunction

Putting the Pieces Together in Gilles de la Tourette Syndrome: Exploring the Link Between Clinical Observations and the Biological Basis of Dysfunction

GABA_A and GABA_B receptor subunit localization on neurochemically identified neurons of the human subthalamic nucleus

Probing the Role of Medication, DBS Electrode Position, and Antidromic Activation on Impulsivity Using a Computational Model of Basal Ganglia

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Functional Circuitry of the Basal Ganglia

Cited by 6 publications

References 48 publications

Putting the Pieces Together in Gilles de la Tourette Syndrome: Exploring the Link Between Clinical Observations and the Biological Basis of Dysfunction

Putting the Pieces Together in Gilles de la Tourette Syndrome: Exploring the Link Between Clinical Observations and the Biological Basis of Dysfunction

GABAA and GABAB receptor subunit localization on neurochemically identified neurons of the human subthalamic nucleus

Probing the Role of Medication, DBS Electrode Position, and Antidromic Activation on Impulsivity Using a Computational Model of Basal Ganglia

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GABA_A and GABA_B receptor subunit localization on neurochemically identified neurons of the human subthalamic nucleus