Segregation of D1 and D2 dopamine receptors in the striatal direct and indirect pathways: An historical perspective

Frontiers in Synaptic Neuroscience, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 19, 2023

The direct and indirect striatal pathways form a cornerstone of the circuits basal ganglia. Dopamine has opponent affects on function these due to segregation D1- D2-dopamine receptors in spiny projection neurons giving rise pathways. An historical perspective is provided discovery dopamine receptor leading models how affect motor behavior.

Language: Английский

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Sex hormones differentially contribute to Parkinson disease in males: A multimodal biomarker study

European Journal of Neurology, Journal Year: 2023, Volume and Issue: 30(7), P. 1983 - 1990

Published: March 27, 2023

Abstract Background and purpose Parkinson disease (PD) presents relevant sex‐related differences in epidemiology, pathophysiology, clinical features, with males being more vulnerable to the disease. Sex hormones might have a role, as experimental models suggest; however, human‐based evidence is scarce. Here, we integrated multimodal biomarkers investigate relationships between circulating sex clinical–pathological features male PD patients. Methods A cohort of 63 patients underwent comprehensive evaluation motor nonmotor disturbances; measurement estradiol, testosterone, follicle‐stimulating hormone (FSH), luteinizing (LH) blood levels; cerebrospinal fluid (CSF) assay total α‐synuclein, amyloid‐β‐42, amyloid‐β‐40, tau, phosphorylated‐181 tau levels. subgroup 47 brain volumetry by 3‐T magnetic resonance imaging for further correlations. control group 56 age‐matched individuals was enrolled comparative analyses. Results Male had higher estradiol testosterone levels than controls. Estradiol independent inverse associations Movement Disorder Society–Unified Parkinson's Disease Rating Scale Part 3 score duration; it also lower nonfluctuating Testosterone correlations CSF α‐synuclein right globus pallidus volume. FSH LH age‐dependent cognitive impairment amyloid‐β‐42/amyloid‐β‐40 ratio. Conclusions The study suggested that could differentially contribute Whereas protective role impairment, be involved vulnerability neuropathology. Gonadotropins instead mediate phenomena amyloidopathy decline.

Language: Английский

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Neural signatures of indirect pathway activity during subthalamic stimulation in Parkinson’s disease

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 11, 2024

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) produces an electrophysiological signature called evoked resonant neural activity (ERNA); a high-frequency oscillation that has been linked to treatment efficacy. However, single-neuron and synaptic bases ERNA are unsubstantiated. This study proposes is subcortical neuronal circuit DBS-mediated engagement basal ganglia indirect pathway network. In people with Parkinson's disease, we: (i) showed each peak waveform associated temporally-locked inhibition in STN; (ii) characterized temporal dynamics ERNA; (iii) identified putative mesocircuit architecture, embedded empirically-derived dynamics, necessary for emergence silico; (iv) localized dorsal STN normative anatomical space; (v) used patient-wise hotspot locations assess spatial relevance respect DBS outcome; (vi) local fiber activation profile derived group-level hotspot.

Language: Английский

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Dopamine depletion can be predicted by the aperiodic component of subthalamic local field potentials

Neurobiology of Disease, Journal Year: 2022, Volume and Issue: 168, P. 105692 - 105692

Published: March 16, 2022

Electrophysiological biomarkers reflecting the pathological activities in basal ganglia are essential to gain an etiological understanding of Parkinson's disease (PD) and develop a method diagnosing treating disease. Previous studies that explored electrophysiological PD have focused mainly on oscillatory or periodic such as beta gamma oscillations. Emerging evidence has suggested nonoscillatory, aperiodic component reflects firing rate synaptic current changes corresponding cognitive states. Nevertheless, it never been thoroughly examined whether can be used biomarker PD. In this study, we parameters hemiparkinsonian rats tested its practicality activity. We found set parameters, offset exponent, were significantly decreased by nigrostriatal lesion. To further prove usefulness biomarkers, acute levodopa treatment reverted offset. then compared with previously established PD, frequency oscillation. low negative correlation power. showed performance machine learning-based prediction improved using both power component, which each other. suggest will provide more sensitive measurement early diagnosis potential use feedback parameter for adaptive deep brain stimulation.

Language: Английский

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Sub-harmonic entrainment of cortical gamma oscillations to deep brain stimulation in Parkinson's disease: Model based predictions and validation in three human subjects

Brain stimulation, Journal Year: 2023, Volume and Issue: 16(5), P. 1412 - 1424

Published: Sept. 1, 2023

The exact mechanisms of deep brain stimulation (DBS) are still an active area investigation, in spite its clinical successes. This is due part to the lack understanding effects on neuronal rhythms. Entrainment oscillations has been hypothesised as a potential mechanism neuromodulation. A better entrainment might further inform existing methods continuous DBS, and help refine algorithms for adaptive methods. purpose this study develop test theoretical framework predict cortical rhythms DBS across wide range parameters. We fit model interacting neural populations selected features characterising PD patients' off-stimulation finely-tuned gamma rhythm recorded through electrocorticography. Using fitted models, we basal ganglia parameters that would result 1:2 entrainment, special case sub-harmonic observed patients predicted by theory. show circuit models patient data exhibit when provided Furthermore, verify key region frequency/amplitude space with follow-up recordings from same patients, such loss above certain amplitudes. Our results reveal continuous, constant frequency may lead nonlinear patterns parameters, these responses can be modelling. Should prove important therapeutic stimulation, our modelling reduce parameter clinicians must consider programming devices optimal benefit.

Language: Английский

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External globus pallidus input to the dorsal striatum regulates habitual seeking behavior in male mice

Nature Communications, Journal Year: 2023, Volume and Issue: 14(1)

Published: July 12, 2023

Abstract The external globus pallidus (GPe) coordinates action-selection through GABAergic projections throughout the basal ganglia. GPe arkypallidal (arky) neurons project exclusively to dorsal striatum, which regulates goal-directed and habitual seeking. However, role of arky in reward-seeking remains unknown. Here, we identified that a majority target dorsolateral striatum (DLS). Using fiber photometry, found activities were higher during random interval (RI; habit) compared ratio (RR; goal) operant conditioning. Support vector machine analysis demonstrated neuron have sufficient information distinguish between RR RI behavior. Genetic ablation this GPe→DLS circuit facilitated shift from Conversely, chemogenetic activation globally reduced seeking behaviors, was blocked by systemic D1R agonism. Our findings reveal constraining male mice, is relevant addictive behaviors other compulsive disorders.

Language: Английский

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Striosomes control dopamine via dual pathways paralleling canonical basal ganglia circuits

Current Biology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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Dynamical mechanism of parkinsonian beta oscillation in a heterogenous subthalamopallidal network

Nonlinear Dynamics, Journal Year: 2023, Volume and Issue: 111(11), P. 10505 - 10527

Published: April 11, 2023

Language: Английский

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Distributed dopaminergic signaling in the basal ganglia and its relationship to motor disability in Parkinson's disease

Current Opinion in Neurobiology, Journal Year: 2023, Volume and Issue: 83, P. 102798 - 102798

Published: Oct. 30, 2023

The degeneration of mesencephalic dopaminergic neurons that innervate the basal ganglia is responsible for cardinal motor symptoms Parkinson's disease (PD). It has been thought loss signaling in one region - striatum was solely network pathophysiology causing PD symptoms. While our understanding dopamine (DA)'s role modulating striatal circuitry deepened recent years, it also become clear acts other regions to influence movement. Underscoring this point, examination a new progressive mouse model shows DA depletion alone not sufficient induce parkinsonism and restoration extra-striatal attenuates parkinsonian deficits once they appear. This review summarizes advances effort understand circuitry, its modulation by DA, how dysfunction drives

Language: Английский

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Distinct basal ganglia contributions to learning from implicit and explicit value signals in perceptual decision-making

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: June 22, 2024

Abstract Metacognitive evaluations of confidence provide an estimate decision accuracy that could guide learning in the absence explicit feedback. We examine how humans might learn from this implicit feedback direct comparison with feedback, using simultaneous EEG-fMRI. Participants performed a motion direction discrimination task where stimulus difficulty was increased to maintain performance, intermixed explicit- and no-feedback trials. isolate single-trial estimates post-decision EEG decoding, find these neural signatures re-emerge at time together separable identified versus along dorsal-ventral gradient striatum, finding uniquely enabled by EEG-fMRI fusion. These two signals appear integrate into aggregate representation external globus pallidus, which broadcast updates improve cortical processing via thalamus insular cortex, irrespective source

Language: Английский

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