Striatal synapses, circuits, and Parkinson's disease

Zhai, Shenyu; Tanimura, Akio; Graves, Steven M.; Shen, Weisen; Surmeier, D. James

doi:10.1016/j.conb.2017.08.004

Cited by 140 publications

(100 citation statements)

References 93 publications

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“…What circuit computations might account for systematic slowing of movement following dopamine depletion? Although it is well established that the chronic absence of dopamine signaling produces dramatic structural and biophysical changes in SPNs, relatively little is known about changes in the activity of SPNs during movement. Theories premised on the antagonistic role of direct and indirect pathways suggest that excessive activation of iSPNs prior to and during movement initiation should be primarily responsible .…”

Section: Activity In Basal Ganglia Circuits Represents Movement Kinemmentioning

confidence: 99%

A Proposed Circuit Computation in Basal Ganglia: History‐Dependent Gain

Yttri

Dudman

2018

Movement Disorders

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In this Scientific Perspectives we first review the recent advances in our understanding of the functional architecture of basal ganglia circuits. Then we argue that these data can best be explained by a model in which basal ganglia act to control the gain of movement kinematics to shape performance based on prior experience, which we refer to as a history‐dependent gain computation. Finally, we discuss how insights from the history‐dependent gain model might translate from the bench to the bedside, primarily the implications for the design of adaptive deep brain stimulation. Thus, we explicate the key empirical and conceptual support for a normative, computational model with substantial explanatory power for the broad role of basal ganglia circuits in health and disease. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Section: Activity In Basal Ganglia Circuits Represents Movement Kinemmentioning

confidence: 99%

A Proposed Circuit Computation in Basal Ganglia: History‐Dependent Gain

Yttri

Dudman

2018

Movement Disorders

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“…The striatum is the brain structure richest in DA and DA receptors, and disorders of DA transmission have quite a profound impact on information processing in this region (Gerfen and Surmeier 2011; Zhai et al 2017). On a functional level, the striatum can be viewed as a hub integrating information about internal states and external stimuli to achieve a dynamic and plastic control of motor behaviour.…”

Section: The Striatummentioning

confidence: 99%

“…Thus, dSPNs express G olf− coupled D1 receptors, which both increase the intrinsic excitability of these cells and promote long-term potentiation (LTP) of their glutamatergic synapses. By contrast, iSPNs express the Gi-coupled D2 receptor, which decreases intrinsic excitability and promotes long-term depression (LTD) of glutamatergic synapses (Nicola et al 2000; Zhai et al 2017). The striatum also contains an extensive network of GABAergic interneurons and cholinergic interneurons, which play key modulatory roles in all aspects of striatal physiology and behaviour (Tanimura et al 2017; Tepper et al 2010).…”

Section: The Striatummentioning

confidence: 99%

On the neuronal circuitry mediating l-DOPA-induced dyskinesia

2018

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With the advent of rodent models of l-DOPA-induced dyskinesia (LID), a growing literature has linked molecular changes in the striatum to the development and expression of abnormal involuntary movements. Changes in information processing at the striatal level are assumed to impact on the activity of downstream basal ganglia nuclei, which in turn influence brain-wide networks, but very little is actually known about systems-level mechanisms of dyskinesia. As an aid to approach this topic, we here review the anatomical and physiological organisation of cortico-basal ganglia-thalamocortical circuits, and the changes affecting these circuits in animal models of parkinsonism and LID. We then review recent findings indicating that an abnormal cerebellar compensation plays a causal role in LID, and that structures outside of the classical motor circuits are implicated too. In summarizing the available data, we also propose hypotheses and identify important knowledge gaps worthy of further investigation. In addition to informing novel therapeutic approaches, the study of LID can provide new clues about the interplay between different brain circuits in the control of movement.

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“…; Zhai et al . ), the direct impact of αSO on glutamatergic striatal projections has not yet been reported.…”

Section: Resultsmentioning

confidence: 95%

α‐synuclein oligomers enhance astrocyte‐induced synapse formation through TGF‐β1 signaling in a Parkinson's disease model

Diniz

Matias

Araújo

et al. 2019

Journal of Neurochemistry

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Parkinson's disease (PD) is characterized by selective death of dopaminergic neurons in the substantia nigra, degeneration of the nigrostriatal pathway, increases in glutamatergic synapses in the striatum and aggregation of α‐synuclein. Evidence suggests that oligomeric species of α‐synuclein (αSO) are the genuine neurotoxins of PD. Although several studies have supported the direct neurotoxic effects of αSO on neurons, their effects on astrocytes have not been directly addressed. Astrocytes are essential to several steps of synapse formation and function, including secretion of synaptogenic factors, control of synaptic elimination and stabilization, secretion of neural/glial modulators, and modulation of extracellular ions, and neurotransmitter levels in the synaptic cleft. Here, we show that αSO induced the astrocyte reactivity and enhanced the synaptogenic capacity of human and murine astrocytes by increasing the levels of the known synaptogenic molecule transforming growth factor beta 1 (TGF‐β1). Moreover, intracerebroventricular injection of αSO in mice increased the number of astrocytes, the density of excitatory synapses, and the levels of TGF‐β1 in the striatum of injected animals. Inhibition of TGF‐β1 signaling impaired the effect of the astrocyte‐conditioned medium on glutamatergic synapse formation in vitro and on striatal synapse formation in vivo, whereas addition of TGF‐β1 protected mesencephalic neurons against synapse loss triggered by αSO. Together, our data suggest that αSO have important effects on astrocytic functions and describe TGF‐β1 as a new endogenous astrocyte‐derived molecule involved in the increase in striatal glutamatergic synaptic density present in early stages of PD. Open Science Badges This article has received a badge for *Open Materials* because it provided all relevant information to reproduce the study in the manuscript. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/. Cover Image for this issue: doi: .

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Striatal synapses, circuits, and Parkinson's disease

Cited by 140 publications

References 93 publications

A Proposed Circuit Computation in Basal Ganglia: History‐Dependent Gain

A Proposed Circuit Computation in Basal Ganglia: History‐Dependent Gain

On the neuronal circuitry mediating l-DOPA-induced dyskinesia

α‐synuclein oligomers enhance astrocyte‐induced synapse formation through TGF‐β1 signaling in a Parkinson's disease model

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