Striatal Cholinergic Interneurons: How to Elucidate Their Function in Health and Disease DOI Creative Commons
Nicolas Mallet, Arthur Leblois, Nicolas Maurice

et al.

Frontiers in Pharmacology, Journal Year: 2019, Volume and Issue: 10

Published: Dec. 13, 2019

Striatal cholinergic interneurons (CINs) are the main source of acetylcholine in striatum and believed to play an important role basal ganglia physiology pathophysiology. The CINs striatal function is known mostly from extracellular recordings tonically active neurons monkeys, which correspond CINs. Because these transiently respond motivationally cues with brief pauses, flanked by bursts increased activity, they classically viewed as key players reward-related learning. However, CIN modulatory within network has been mainly inferred action agonists/antagonists or through activation. These manipulations far recapitulating activity response behaviorally-relevant stimuli. New technical tools such optogenetics allow researchers specifically manipulate this sparse neuronal population mimic their typical pause response. For example, it now possible investigate how short inhibition shapes properties. Here, we review most recent literature show new techniques have brought considerable insights into functional normal pathological states, raising several interesting novel questions. To continue moving forward, crucial determine detail changes during behavior, particularly rodents. We will also discuss computational approaches combined contribute further our understanding circuits.

Language: Английский

Unravelling cell type-specific responses to Parkinson’s Disease at single cell resolution DOI Creative Commons
Araks Martirosyan, Rizwan Ansari, Francisco Pestana

et al.

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: Jan. 20, 2024

Abstract Parkinson’s Disease (PD) is the second most common neurodegenerative disorder. The pathological hallmark of PD loss dopaminergic neurons and presence aggregated α-synuclein, primarily in substantia nigra pars compacta (SNpc) midbrain. However, molecular mechanisms that underlie pathology different cell types not currently understood. Here, we present a single nucleus transcriptome analysis human post-mortem SNpc obtained from 15 sporadic cases 14 Controls. Our dataset comprises ∼84K nuclei, representing all major brain, allowing us to obtain transcriptome-level characterization these types. Importantly, identify multiple subpopulations for each type describe specific gene sets provide insights into differing roles subpopulations. findings reveal significant decrease neuronal cells samples, accompanied by an increase glial T cells. Subpopulation analyses demonstrate depletion tyrosine hydroxylase ( TH ) enriched astrocyte, microglia oligodendrocyte populations as well neurons, which are also depleted. Moreover, marker depleted identified 28 overlapping genes, including those associated with dopamine metabolism (e.g., ALDH1A1, SLC6A3 & SLC18A2 ). Overall, our study provides valuable resource understanding involved neuron degeneration responses PD, highlighting existence novel type-specific sets.

Language: Английский

Citations

33
Sleep disorders cause Parkinson's disease or the reverse is true: Good GABA good night DOI Creative Commons
Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb,

Ali K. Albuhadily

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(3)

Published: March 1, 2024

Parkinson's disease (PD) is a progressive neurodegenerative brain due to degeneration of dopaminergic neurons (DNs) presented with motor and non-motor symptoms. PD symptoms are developed in response the disturbance diverse neurotransmitters including γ-aminobutyric acid (GABA). GABA has neuroprotective effect against neuropathology by protecting DNs substantia nigra pars compacta (SNpc). It been shown that GABAergic linked progression neurotransmission necessary pathway for normal sleep patterns, thus deregulation could be potential cause disorders PD.

Language: Английский

Citations

18
Role of GABA pathway in motor and non-motor symptoms in Parkinson's disease: a bidirectional circuit DOI Creative Commons

Bandar Alharbi,

Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb

et al.

European journal of medical research, Journal Year: 2024, Volume and Issue: 29(1)

Published: March 27, 2024

Abstract Parkinson's disease (PD) is a progressive neurodegenerative as result of the degeneration dopaminergic neurons in substantia nigra pars compacta (SNpc). The fundamental features PD are motor and non-motor symptoms. symptoms develop due to disruption neurotransmitters other such γ-aminobutyric acid (GABA). potential role GABA neuropathology concerning was not precisely discussed. Therefore, this review intended illustrate possible regarding pathway essential regulating inhibitory tone prevent excessive stimulation cerebral cortex. Degeneration linked with reducing GABAergic neurotransmission. Decreasing activity promotes mitochondrial dysfunction oxidative stress, which highly related neuropathology. Hence, restoring by agonists may attenuate progression dysregulation SNpc contributes developing Besides, also pathway, amelioration reduce In conclusion, deregulation might be intricate Improving novel, beneficial approach control

Language: Английский

Citations

16
Transcriptional complexity in the insect central complex: single nuclei RNA-sequencing of adult brain neurons derived from type 2 neuroblasts DOI Open Access
Derek Epiney, Gonzalo N Morales Chaya, Noah Dillon

et al.

Published: Feb. 27, 2025

In both invertebrates such as Drosophila and vertebrates mouse or human, the brain contains most diverse population of cell types any tissue. It is generally accepted that transcriptional diversity an early step in generating neuronal glial diversity, followed by establishment a unique gene expression profile determines morphology, connectivity, function. , there are two neural stem cells, called Type 1 (T1) 2 (T2) neuroblasts. contrast to T1 neuroblasts, T2 neuroblasts generate intermediate progenitors (INPs) expand number types. The T2-derived neurons contributes large portion central complex (CX), conserved region plays role sensorimotor integration. Recent work has revealed much connectome CX, but how this assembled remains unclear. Mapping derived from necessary linking assembly adult brain. Here we perform single nuclei RNA sequencing neuroblast-derived glia. We identify clusters containing all known classes glia, male/female enriched, 161 neuron-specific clusters. map neurotransmitter neuropeptide transcription factor combinatorial codes for each cluster (presumptive neuron subtype). This directs functional studies determine whether code specifies distinct type within CX. several columnar subtypes (NPF+ AstA+) closely related Our data support hypothesis represents one few subtypes.

Language: Английский

Citations

2
MicroRNAs as regulators of brain function and targets for treatment of epilepsy DOI
Gary P. Brennan, David C. Henshall

Nature Reviews Neurology, Journal Year: 2020, Volume and Issue: 16(9), P. 506 - 519

Published: June 16, 2020

Language: Английский

Citations

128
New Insights Into Cholinergic Neuron Diversity DOI Creative Commons
Noorya Yasmin Ahmed,

Rhys Knowles,

Nathalie Dehorter

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2019, Volume and Issue: 12

Published: Aug. 27, 2019

Cholinergic neurons comprise a small population of cells in the striatum but have fundamental roles fine tuning brain function, and aetiology neurological psychiatric disorders such as Parkinson's disease or schizophrenia. The process developmental cell specification underlying neuronal identity function is an area great current interest. There has been significant progress identifying origins, commonalities molecular markers, physiological properties cholinergic neurons. Currently, we are aware number key factors that promote fate during development. However, extent diversity still largely underestimated. Recent evidence shown new insight on biological basis their specification, indicating may be far more diverse than previously thought. This review highlights features synaptic segregate subtypes. It provides accurate picture organization networks. also discusses challenges deciphering logic heterogeneity plays role control neural processes health disease.

Language: Английский

Citations

87
Parkinson's disease motor symptoms rescue by CRISPRa‐reprogramming astrocytes into GABAergic neurons DOI

Jessica Giehrl‐Schwab,

Florian Giesert, Benedict Rauser

et al.

EMBO Molecular Medicine, Journal Year: 2022, Volume and Issue: 14(5)

Published: April 4, 2022

Language: Английский

Citations

51
Cation-Chloride Cotransporters KCC2 and NKCC1 as Therapeutic Targets in Neurological and Neuropsychiatric Disorders DOI Creative Commons

Patricia Lam,

Julia Newland,

Richard L. M. Faull

et al.

Molecules, Journal Year: 2023, Volume and Issue: 28(3), P. 1344 - 1344

Published: Jan. 31, 2023

Neurological diseases including Alzheimer’s, Huntington’s disease, Parkinson’s Down syndrome and epilepsy, neuropsychiatric disorders such as schizophrenia, are conditions that affect not only individuals but societies on a global scale. Current therapies offer means for small symptomatic relief, recently there has been increasing demand therapeutic alternatives. The γ-aminobutyric acid (GABA)ergic signaling system investigated developing new it noted any dysfunction or changes to this can contribute disease progression. Expression of the K-Cl-2 (KCC2) N-K-C1-1 (NKCC1) cation-chloride cotransporters (CCCs) linked disruption GABAergic activity by affecting polarity GABAA receptor signaling. KCC2 NKCC1 play part in multiple neurological disorders, making them target interest potential therapies. This review explores current research suggesting pathophysiological role importance disorders.

Language: Английский

Citations

29
GABA co-released from striatal dopamine axons dampens phasic dopamine release through autoregulatory GABAA receptors DOI Creative Commons
Jyoti C. Patel,

Ang D. Sherpa,

Riccardo Melani

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(3), P. 113834 - 113834

Published: March 1, 2024

Striatal dopamine axons co-release and gamma-aminobutyric acid (GABA), using GABA provided by uptake via transporter-1 (GAT1). Functions of are poorly understood. We asked whether co-released autoinhibits release axonal type A receptors (GABAARs), complementing established inhibition acting at D2 autoreceptors. show that express α3-GABAAR subunits in mouse striatum. Enhanced evoked single-pulse optical stimulation striatal slices with GABAAR antagonism confirms an endogenous tone limits release. Strikingly, additional inhibitory component is seen when multiple pulses used to mimic phasic activity, revealing the role GABAAR-mediated autoinhibition This autoregulation lost conditional GAT1-knockout mice lacking co-release. Given faster kinetics ionotropic GABAARs than G-protein-coupled autoreceptors, our data reveal a mechanism whereby acts as first responder dampen phasic-to-tonic signaling.

Language: Английский

Citations

15
A new advanced cellular model of functional cholinergic-like neurons developed by reprogramming the human SH-SY5Y neuroblastoma cell line DOI Creative Commons
Alessia D’Aloia, Valentina Pastori, Stefania Blasa

et al.

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 12, 2024

Abstract Modeling human neuronal properties in physiological and pathological conditions is essential to identify novel potential drugs explore mechanisms of neurological diseases. For this purpose, we generated a three-dimensional (3D) culture, by employing the readily available neuroblastoma SH-SY5Y cell line, new differentiation protocol. The entire process occurred matrix lasted 47 days, with 7 days pre-differentiation phase 40 differentiation, allowed development 3D culture consistent environment. Neurons were electrically active, able establish functional networks, showed features cholinergic neurons. Hence here provide an easily accessible, reproducible, suitable method that might empower studies on synaptic function, vesicle trafficking, metabolism, which sustain activity cerebral circuits. Moreover, protocol could represent promising cellular tool study processes, such as migration, maturation, develop therapeutic approaches.

Language: Английский

Citations

11