Bicuculline-Induced Chorea Manifests in Focal Rather Than Globalized Abnormalities in the Activation of the External and Internal Globus Pallidus

Bronfeld, Maya; Belelovsky, Katya; Erez, Yaara; Bugaysen, Jenia; Korngreen, Alon; Bar‐Gad, Izhar

doi:10.1152/jn.00093.2010

Cited by 24 publications

(20 citation statements)

References 62 publications

(54 reference statements)

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“…Selective anatomical and functional abnormalities in the cortico-BG system have been observed in patients suffering from disorders such as Parkinson's disease (Agid, 1991), Huntington's chorea (Glass et al, 2000; Deng et al, 2004), dystonia (Marsden et al, 1985), and motor tics (Singer and Minzer, 2003), which were therefore considered “BG-related movement disorders.” Animal models and anecdotal findings in human patients confirmed that localized dysfunctions (inactivation or disinhibition) of different parts of the BG could directly induce behavioral abnormalities similar to the symptoms observed in these disorders (Martin and Alcock, 1934; Crossman et al, 1988; Hamada and DeLong, 1992; Grabli et al, 2004; Desmurget and Turner, 2008; McCairn et al, 2009; Bronfeld et al, 2010). The exact nature of the abnormal symptoms has been related to the type and location of the BG dysfunction.…”

Section: The Basal Gangliamentioning

confidence: 81%

Loss of Specificity in Basal Ganglia Related Movement Disorders

Bronfeld¹,

Bar‐Gad²

2011

Front. Syst. Neurosci.

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The basal ganglia (BG) are a group of interconnected nuclei which play a pivotal part in limbic, associative, and motor functions. This role is mirrored by the wide range of motor and behavioral abnormalities directly resulting from dysfunction of the BG. Studies of normal behavior have found that BG neurons tend to phasically modulate their activity in relation to different behavioral events. In the normal BG, this modulation is highly specific, with each neuron related only to a small subset of behavioral events depending on specific combinations of movement parameters and context. In many pathological conditions involving BG dysfunction and motor abnormalities, this neuronal specificity is lost. Loss of specificity (LOS) manifests in neuronal activity related to a larger spectrum of events and consequently a large overlap of movement-related activation patterns between different neurons. We review the existing evidence for LOS in BG-related movement disorders, the possible neural mechanisms underlying LOS, its effects on frequently used measures of neuronal activity and its relation to theoretical models of the BG. The prevalence of LOS in a many BG-related disorders suggests that neuronal specificity may represent a key feature of normal information processing in the BG system. Thus, the concept of neuronal specificity may underlie a unifying conceptual framework for the BG role in normal and abnormal motor control.

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Section: The Basal Gangliamentioning

confidence: 81%

Loss of Specificity in Basal Ganglia Related Movement Disorders

Bronfeld¹,

Bar‐Gad²

2011

Front. Syst. Neurosci.

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“…(6) The additional hyper-behavioral symptoms (hyperactivity and contraversive circling) which sometimes followed microinjections were common to both species. Such behaviors have been observed in both monkeys (Grabli et al, 2004; Worbe et al, 2009; Bronfeld et al, 2010) and rats (Wisniecki et al, 2003; Ikeda et al, 2010) following microinjections of GABA A antagonists into the striatum or into an adjacent BG nucleus—the GPe. In the current study, hyperbehavioral symptoms were more common following microinjections into the posterior striatum, a location which is closer to the striatum-GPe border, compared with the anterior striatum location.…”

Section: Discussionmentioning

confidence: 96%

Motor tics evoked by striatal disinhibition in the rat

Bronfeld¹,

Yael²,

Belelovsky³

et al. 2013

Front. Syst. Neurosci.

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Motor tics are sudden, brief, repetitive movements that constitute the main symptom of Tourette syndrome (TS). Multiple lines of evidence suggest the involvement of the cortico-basal ganglia system, and in particular the basal ganglia input structure—the striatum in tic formation. The striatum receives somatotopically organized cortical projections and contains an internal GABAergic network of interneurons and projection neurons' collaterals. Disruption of local striatal GABAergic connectivity has been associated with TS and was found to induce abnormal movements in model animals. We have previously described the behavioral and neurophysiological characteristics of motor tics induced in monkeys by local striatal microinjections of the GABAA antagonist bicuculline. In the current study we explored the abnormal movements induced by a similar manipulation in freely moving rats. We targeted microinjections to different parts of the dorsal striatum, and examined the effects of this manipulation on the induced tic properties, such as latency, duration, and somatic localization. Tics induced by striatal disinhibition in monkeys and rats shared multiple properties: tics began within several minutes after microinjection, were expressed solely in the contralateral side, and waxed and waned around a mean inter-tic interval of 1–4 s. A clear somatotopic organization was observed only in rats, where injections to the anterior or posterior striatum led to tics in the forelimb or hindlimb areas, respectively. These results suggest that striatal disinhibition in the rat may be used to model motor tics such as observed in TS. Establishing this reliable and accessible animal model could facilitate the study of the neural mechanisms underlying motor tics, and the testing of potential therapies for tic disorders.

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“…The critical role of the GP in the control of movement is illustrated by the abnormal activity of GP neurons in movement disorders, including the increased firing rates in the GP in Huntington's disease (Starr et al, 2008) and beta oscillations of the GP neurons in Parkinson's disease (PD) (Mallet et al, 2008). Consistent with the critical role of the GP in basal ganglia circuits and behavior, quinolinic acid lesion of the GP leads to a decrease in spontaneous movement (Hauber et al, 1998) and activation of GP neurons by the microinjection of the GABAA receptor antagonist bicuculline (Matsumura et al, 1995) into the GP induces spontaneous movement (Grabli et al, 2004) and dyskinesia in primates (Crossman et al, 1984; Bronfeld et al, 2010). …”

Section: Introductionmentioning

confidence: 83%

Optogenetic Stimulation of GABAergic Neurons in the Globus Pallidus Produces Hyperkinesia

Tian

Yan

Wang

et al. 2018

Front. Behav. Neurosci.

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The globus pallidus (GP) is emerging as a critical locus of basal ganglia control of motor activity, but the exact role of GABAergic GP neurons remain to be defined. By targeted expression of channelrhodopsin 2 (ChR2) in GABAergic neurons using the VGAT-ChR2-EYFP transgenic mice, we showed that optogenetic stimulation of GABAergic neurons in the right GP produced hyperkinesia. Optogenetic stimulation of GABAergic GP neurons increased c-Fos-positive cells in GP, M1 cortex, and caudate-putamen (CPu), and decreased c-Fos-positive cells in entopeduncular nucleus (EPN), compared to the contralateral hemisphere. In agreement with the canonical basal ganglia model. Furthermore, we delivered AAV-CaMKIIα-ChR2-mCherry virus to the excitatory neurons of the subthalamic nucleus (STN) and selectively stimulated glutamatergic afferent fibers from the STN onto the GP. This optogenetic stimulation produced abnormal movements, similar to the behaviors that observed in the VGAT-ChR2-EYFP transgenic mice. Meanwhile, we found that the c-Fos expression pattern in the GP, M1, STN, EPN, and CPu produced by optogenetic activation of glutamatergic afferent fibers from the STN in GP was similar to the c-Fos expression pattern in the VGAT-ChR2-EYFP transgenic mice. Taken together, our results suggest that excess GP GABAergic neurons activity could be the neural substrate of abnormal involuntary movements in hyperkinetic movement disorders. The neural circuitry underlying the abnormal involuntary movements is associated with excessive GP, M1, CPu activity, and reduced EPN activity. Inhibition of GP GABAergic neurons represents new treatment targets for hyperkinetic movement disorder.

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Bicuculline-Induced Chorea Manifests in Focal Rather Than Globalized Abnormalities in the Activation of the External and Internal Globus Pallidus

Cited by 24 publications

References 62 publications

Loss of Specificity in Basal Ganglia Related Movement Disorders

Loss of Specificity in Basal Ganglia Related Movement Disorders

Motor tics evoked by striatal disinhibition in the rat

Optogenetic Stimulation of GABAergic Neurons in the Globus Pallidus Produces Hyperkinesia

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