Optogenetic activation of striatal cholinergic interneurons regulates L-dopa-induced dyskinesias

Bordia, Tanuja; Perez, Xiomara A.; Heiss, Jaime E.; Zhang, Danhui; Quik, Maryka

doi:10.1016/j.nbd.2016.02.019

Cited by 68 publications

(98 citation statements)

References 84 publications

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“…Mecamylamine was then injected and 30 min later the mouse was again optically stimulated and rated. The effect of mecamylamine was evaluated 30 min after injection consistent with previous work (Bordia et al, 2010; Bordia et al, 2016; Dekundy et al, 2007). …”

Section: Methodsmentioning

confidence: 99%

“…Eight wk after pellet implantation, the effect of optical illumination was determined, as described (Bordia et al, 2016). ChR2 was activated using a 473 nm diode laser adjusted such that the power was 1 mW at each fiber tip.…”

Section: Methodsmentioning

confidence: 99%

“…Mice were killed by cervical dislocation and immunohistochemistry done as described (Bordia et al, 2016). The brains were quickly removed, fixed in 4% paraformaldehyde for 2–3 day and cryopreserved in 10–30% sucrose for 3 days.…”

Section: Methodsmentioning

confidence: 99%

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Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia

Bordia

Zhang

Perez

et al. 2016

Experimental Neurology

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Tardive dyskinesia (TD) is a drug-induced movement disorder that arises with antipsychotics. These drugs are the mainstay of treatment for schizophrenia and bipolar disorder, and are also prescribed for major depression, autism, attention deficit hyperactivity, obsessive compulsive and post-traumatic stress disorder. There is thus a need for therapies to reduce TD. The present studies and our previous work show that nicotine administration decreases haloperidol-induced vacuous chewing movements (VCMs) in rodent TD models, suggesting a role for the nicotinic cholinergic system. Extensive studies also show that D2 dopamine receptors are critical to TD. However, the precise involvement of striatal cholinergic interneurons and D2 medium spiny neurons (MSNs) in TD is uncertain. To elucidate their role, we used optogenetics with a focus on the striatum because of its close links to TD. Optical stimulation of striatal cholinergic interneurons using cholineacetyltransferase (ChAT)-Cre mice expressing channelrhodopsin2-eYFP decreased haloperidol-induced VCMs (~50%), with no effect in control-eYFP mice. Activation of striatal D2 MSNs using Adora2a-Cre mice expressing channelrhodopsin2-eYFP also diminished antipsychotic-induced VCMs, with no change in control-eYFP mice. In both ChAT-Cre and Adora2a-Cre mice, stimulation or mecamylamine alone similarly decreased VCMs with no further decline with combined treatment, suggesting nAChRs are involved. Striatal D2 MSN activation in haloperidol-treated Adora2a-Cre mice increased c-Fos+ D2 MSNs and decreased c-Fos+ non-D2 MSNs, suggesting a role for c-Fos. These studies provide the first evidence that optogenetic stimulation of striatal cholinergic interneurons and GABAergic MSNs modulates VCMs, and thus possibly TD. Moreover, they suggest nicotinic receptor drugs may reduce antipsychotic-induced TD.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia

Bordia

Zhang

Perez

et al. 2016

Experimental Neurology

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“…The increase in ERK activity observed in Chl is indicative of increased excitability, which may be causally related to LID. This is supported by the observation that, in a mouse model of PD, short-pulse optogenetic stimulation of Chl exacerbates the dyskinetic response to l -DOPA (Bordia et al 2016). Conversely, in the same PD model, LID is reduced by interventions that counteract Chl hyper-excitability by antagonizing excitatory histamine H2 receptors, whose activity is pathologically enhanced in the Chl of dyskinetic mice (Lim et al 2015).…”

Section: Extracellular Signal-regulated Kinases 1/2: Central Players mentioning

confidence: 82%

Signal transduction in l-DOPA-induced dyskinesia: from receptor sensitization to abnormal gene expression

Spigolon

Fisone

2018

J Neural Transm

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A large number of signaling abnormalities have been implicated in the emergence and expression of l-DOPA-induced dyskinesia (LID). The primary cause for many of these changes is the development of sensitization at dopamine receptors located on striatal projection neurons (SPN). This initial priming, which is particularly evident at the level of dopamine D1 receptors (D1R), can be viewed as a homeostatic response to dopamine depletion and is further exacerbated by chronic administration of l-DOPA, through a variety of mechanisms affecting various components of the G-protein-coupled receptor machinery. Sensitization of dopamine receptors in combination with pulsatile administration of l-DOPA leads to intermittent and coordinated hyperactivation of signal transduction cascades, ultimately resulting in long-term modifications of gene expression and protein synthesis. A detailed mapping of these pathological changes and of their involvement in LID has been produced during the last decade. According to this emerging picture, activation of sensitized D1R results in the stimulation of cAMP-dependent protein kinase and of the dopamine- and cAMP-regulated phosphoprotein of 32 kDa. This, in turn, activates the extracellular signal-regulated kinases 1 and 2 (ERK), leading to chromatin remodeling and aberrant gene transcription. Dysregulated ERK results also in the stimulation of the mammalian target of rapamycin complex 1, which promotes protein synthesis. Enhanced levels of multiple effector targets, including several transcription factors have been implicated in LID and associated changes in synaptic plasticity and morphology. This article provides an overview of the intracellular modifications occurring in SPN and associated with LID.

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“…Indeed, the current literature on the topic does not present any research on the translation of optogenetic treatment into any neurogenerative models expressing similar symptomology, requiring further research in this field (Ahmad, Ashraf, & Komai, 2015;Bordia, Perez, Heiss, Zhang, & Quik, 2016;Bryson, Machado, Lieberam, & Greensmith, 2016;Jazayeri & Remington, 2016). This review paper will assess the potential use of optogenetics in the development of therapies for MS related symptoms such as cognitive impairment, visual impairment, bladder/bowel dysfunction, and tremors.…”

Section: Current Delivery Strategies and Therapeutic Obstaclesmentioning

confidence: 99%

Therapeutic Potential of Optogenetic Treatment for Individuals with Multiple Sclerosis

Koussy¹,

Jadavji²

2017

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Optogenetic activation of striatal cholinergic interneurons regulates L-dopa-induced dyskinesias

Cited by 68 publications

References 84 publications

Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia

Striatal cholinergic interneurons and D2 receptor-expressing GABAergic medium spiny neurons regulate tardive dyskinesia

Signal transduction in l-DOPA-induced dyskinesia: from receptor sensitization to abnormal gene expression

Therapeutic Potential of Optogenetic Treatment for Individuals with Multiple Sclerosis

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