Current approaches to characterize micro- and macroscale circuit mechanisms of Parkinson’s disease in rodent models

Peng, Yangfan; Schöneberg, Nina; Esposito, Maria Soledad; Geiger, Jörg R. P.; Sharott, Andrew; Tovote, Philip

doi:10.1016/j.expneurol.2022.114008

Cited by 7 publications

(5 citation statements)

References 215 publications

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“…For treating motor symptoms, the dorsolateral subthalamic nucleus (STN) is widely used as a stimulation target and, to some extent, also the globus pallidus interna (GPi) [ 4 , 5 ]. In PD, the loss of dopaminergic neurons in the substantia nigra correlates with PD symptom severity, in particular bradykinesia and rigidity [ 6 , 7 ]. With DBS treatment, these symptoms can be alleviated, and there are several proposed mechanisms of action [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Physiological effects include direct inhibition of neural activity caused by the activation of inhibitory axons, especially with high-frequency stimulation (>130 Hz), or direct excitation of neural activity. Other proposed mechanisms are “jamming” or information lesion, in which stimulation provides local transmission block, and synaptic filtering [ 6 , 7 , 8 ]. DBS might act as a filter, permitting modulation of the activated neurons [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Real-Life Experience on Directional Deep Brain Stimulation in Patients with Advanced Parkinson’s Disease

Koivu

Scheperjans

Eerola‐Rautio

et al. 2022

JPM

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Directional deep brain stimulation (dDBS) is preferred by patients with advanced Parkinson’s disease (PD) and by programming neurologists. However, real-life data of dDBS use is still scarce. We reviewed the clinical data of 53 PD patients with dDBS to 18 months of follow-up. Directional stimulation was favored in 70.5% of dDBS leads, and single segment activation (SSA) was used in 60% of dDBS leads. Current with SSA was significantly lower than with other stimulation types. During the 6-month follow-up, a 44% improvement in the Unified Parkinson’s Disease Rating Scale (UPDRS-III) points and a 43% decline in the levodopa equivalent daily dosage (LEDD) was observed. After 18 months of follow-up, a 35% LEDD decrease was still noted. The Hoehn and Yahr (H&Y) stages and scores on item no 30 “postural stability” in UPDRS-III remained lower throughout the follow-up compared to baseline. Additionally, dDBS relieved non-motor symptoms during the 6 months of follow-up. Patients with bilateral SSA had similar clinical outcomes to those with other stimulation types. Directional stimulation appears to effectively reduce both motor and non-motor symptoms in advanced PD with minimal adverse effects in real-life clinical care.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Real-Life Experience on Directional Deep Brain Stimulation in Patients with Advanced Parkinson’s Disease

Koivu

Scheperjans

Eerola‐Rautio

et al. 2022

JPM

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“…The method reported in this study could activate the Ca 2+ activities of any target individual cochlear cell. Recently, Ca 2+ fluorescent indicators have been widely used in neuroscience as an alternative to electrical activity patterns. − Many cells can be recorded simultaneously using time-lapse microscopy of Ca 2+ fluorescence, which could be located exactly at each individual neuron.…”

Section: Discussionmentioning

confidence: 99%

Store-Operated Ca²⁺ Channels Contribute to the Generation of Ca²⁺ Waves in Interdental Cells in the Cochleae

Zhang

et al. 2023

ACS Chem. Neurosci.

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Cochlear calcium (Ca2+) waves are vital regulators of the cochlear development and establishment of hearing function. Inner supporting cells are believed to be the main region generating Ca2+ waves that work as internal stimuli to coordinate the development of hair cells and the mapping of neurons in the cochlea. However, Ca2+ waves in interdental cells (IDCs) that connect to inner supporting cells and spiral ganglion neurons are rarely observed and poorly understood. Herein, we reported the mechanism of IDC Ca2+ wave formation and propagation by developing a single-cell Ca2+ excitation technology, which can easily be accomplished using a two-photon microscope for simultaneous microscopy and femtosecond laser Ca2+ excitation in any target individual cell in fresh cochlear tissues. We demonstrated that the store-operated Ca2+ channels in IDCs are responsible for Ca2+ wave formation in these cells. The specific architecture of the IDCs determines the propagation of Ca2+ waves. Our results provide the mechanism of Ca2+ formation in IDCs and a controllable, precise, and noninvasive technology to excite local Ca2+ waves in the cochlea, with good potential for research on cochlear Ca2+ and hearing functions.

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“…Recent studies have started to address the neuronal circuit level as a main unit of brain function, and thus crucial to complement our understanding of the disease. They reveal how not only individual brain regions, but brain-wide networks are impacted 16 , characterizing PD as a "circuitopathy" 17 . This is reflected, for example, by differences in the sensitivity among dopaminergic neurons to αSyn overexpression 18 .…”

Section: Introductionmentioning

confidence: 99%

“…Those emerging concepts highlight the importance of cell-type heterogeneity within brain areas, as well as the synaptic connections from major cellular elements affected in PD with other neuronal populations. Hence, models that allow cell-type-specific induction of PD pathomechanisms are required to dissect the contribution of individual circuit elements to PD symptoms 17 . Consequently, we generated a conditional adeno-associated viral vector (AAV) that allows expression of pαSyn in selected neuronal subtypes using the Cre-lox site-specific recombination system 19,20 .…”

Section: Introductionmentioning

confidence: 99%

A viral vector model for circuit-specific synucleinopathy

Lantheaume,

Schöneberg,

Rodriguez-Rozada

et al. 2023

Preprint

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In Parkinson’s disease (PD), pathomechanisms such as aberrant network dysfunctions can be elucidated by conducting multiscale explorations in animal models. However, the lack of specificity in the existing models limits a restricted targeting of individual network elements and characterization of PD as a “circuitopathy”. We therefore developed a cell-type specific viral vector (AAV2/9-CreON-A53T-αSyn) mouse model that allows to induce synucleinopathy within individual circuit elementsin vivo. When specifically targeted to dopaminergic (DA) neurons of the substantia nigra pars compacta (SNc), our approach recapitulates the main hallmarks of the disease, namely Lewy-body-like aggregation, progressive cellular and nigrostriatal projections loss, together with locomotor impairment. Our strategy is supported by new state-of-the-art analytical approaches for cell quantification and behavior characterization. Altogether, we provide a novel model of synucleinopathy, which offers new opportunities to study the contribution of individual network elements to disease pathomechanisms.

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Current approaches to characterize micro- and macroscale circuit mechanisms of Parkinson’s disease in rodent models

Cited by 7 publications

References 215 publications

Real-Life Experience on Directional Deep Brain Stimulation in Patients with Advanced Parkinson’s Disease

Real-Life Experience on Directional Deep Brain Stimulation in Patients with Advanced Parkinson’s Disease

Store-Operated Ca²⁺ Channels Contribute to the Generation of Ca²⁺ Waves in Interdental Cells in the Cochleae

A viral vector model for circuit-specific synucleinopathy

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Current approaches to characterize micro- and macroscale circuit mechanisms of Parkinson’s disease in rodent models

Cited by 7 publications

References 215 publications

Real-Life Experience on Directional Deep Brain Stimulation in Patients with Advanced Parkinson’s Disease

Real-Life Experience on Directional Deep Brain Stimulation in Patients with Advanced Parkinson’s Disease

Store-Operated Ca2+ Channels Contribute to the Generation of Ca2+ Waves in Interdental Cells in the Cochleae

A viral vector model for circuit-specific synucleinopathy

Contact Info

Product

Resources

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Store-Operated Ca²⁺ Channels Contribute to the Generation of Ca²⁺ Waves in Interdental Cells in the Cochleae