Review
Neurosciences
Maxime Assous
Summary: Acetylcholine plays a critical role in the basal ganglia, particularly in patients with Parkinson's disease, Tourette syndrome, and dystonia. The striatum's cholinergic interneurons are responsible for the bulk of acetylcholine in the structure, and acetylcholine modulates striatal circuits through muscarinic and nicotinic receptors in various combinations. Understanding the expression and function of striatal nicotinic receptors may help develop targeted pharmacological interventions for brain disorders like Parkinson's disease, Tourette syndrome, dystonia, and nicotine addiction.
EUROPEAN JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Ornela Kljakic, Helena Janickova, Miguel Skirzewski, Amy Reichelt, Sara Memar, Salah El Mestikawy, Yulong Li, Lisa M. Saksida, Timothy J. Bussey, Vania F. Prado, Marco A. M. Prado
Summary: In the striatum, cholinergic interneurons can release both acetylcholine and glutamate, and their individual and combined contributions to behavior regulation were assessed in mice using reward-based touchscreen tests. Changes in VAChT and VGLUT3 levels have different effects on reward responses, and the simultaneous loss of both vesicular transporters affects dopamine signaling and behavior in a more severe way than the loss of VAChT alone. This shows that the ability of CINs to secrete two different neurotransmitters allows for complex modulation of various behaviors.
Article
Neurosciences
Nicola B. Mercuri, Mauro Federici, Francesca Romana Rizzo, Lorenzo Maugeri, Sebastian L. D'Addario, Rossella Ventura, Nicola Berretta
Summary: The activation of metabotropic glutamate receptors leads to a prolonged depression of striatal dopamine release and enhances firing of cholinergic interneurons, resulting in anxiety-like behavior.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2021)
Article
Cell Biology
Samet Kocaturk, Elif Beyza Guven, Fulva Shah, James M. Tepper, Maxime Assous
Summary: Cholinergic interneurons play crucial roles in striatal circuits and functions. The activation of acetylcholine signal via muscarinic receptors is well studied, but recent data suggest that nicotinic receptors located on GABAergic interneurons are equally important. Stimulation of cholinergic interneurons activates these receptors and leads to inhibitory effects on striatal projection neurons.
Editorial Material
Multidisciplinary Sciences
Anna E. Ingebretson, Julia C. Lemos
Summary: A new role has been discovered for the ubiquitous integrated stress response pathway in striatal-dependent learning and memory.
Article
Multidisciplinary Sciences
Himanshu Gangal, Xueyi Xie, Zhenbo Huang, Yifeng Cheng, Xuehua Wang, Jiayi Lu, Xiaowen Zhuang, Amanda Essoh, Yufei Huang, Ruifeng Chen, Laura N. Smith, Rachel J. Smith, Jun Wang
Summary: Addictive substances may impair cognitive flexibility. Here the authors show that in rodents, increased activity of striatal direct-pathway medium spiny neurons (dMSNs) in response to cocaine inhibits cholinergic interneurons (CINs), reducing cognitive flexibility.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Natalia Lozovaya, Sanaz Eftekhari, Constance Hammond
Summary: Electrophysiological recordings show that early excitatory cholinergic-GABAergic microcircuits are crucial for the maturation of GABAergic inhibition in the mouse striatum. Cholinergic interneurons in the striatum activate local GABAergic inhibitory microcircuits, which play a role in action selection and associative learning. The study focuses on dual cholinergic/GABAergic interneurons (CGINs) and finds that their morphological and electrophysiological properties rapidly develop during the first post-natal week.
COMMUNICATIONS BIOLOGY
(2023)
Article
Clinical Neurology
Jung-Chieh Du, Man-Hsin Chang, Chen-Jiun Yeh, Ming Tatt Lee, Hsin-Jung Lee, Shu-Hui Chuang, Lih-Chu Chiou
Summary: The SLITRK1 gene mutation and loss of striatal cholinergic interneurons (ChIs) are associated with Tourette syndrome (TS). In a mouse model, Slitrk1-KD mice exhibited TS-like tic behaviors, impaired prepulse inhibition, and delayed sensorimotor response. These characteristics were correlated with lower levels of striatal Slitrk1 protein, fewer Slitrk1-containing ChIs, and fewer activated ChIs in Slitrk1-KD mice.
ANNALS OF NEUROLOGY
(2023)
Article
Neurosciences
Paola Cristofari, Mazarine Desplanque, Odile Poirel, Alison Hebert, Sylvie Dumas, Etienne Herzog, Lydia Danglot, David Geny, Jean-Francois Gilles, Audrey Geeverding, Susanne Bolte, Alexis Canette, Michael Trichet, Veronique Fabre, Stephanie Daumas, Nicolas Pietrancosta, Salah El Mestikawy, Veronique Bernard
Summary: This study used super-resolution microscopy to investigate the release mechanism of acetylcholine and glutamate in striatal cholinergic interneurons. The results showed that some neurons contain both acetylcholine and glutamate in their vesicles, while others only contain one of the two. These findings indicate that striatal cholinergic interneurons have a diverse and complex signaling mechanism.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Yuan Cai, Beatriz E. Nielsen, Emma E. Boxer, Jason Aoto, Christopher P. Ford
Summary: Progressive loss of dopamine inputs in Parkinson's disease leads to imbalances in coordinated signaling of dopamine and acetylcholine in the striatum, contributing to motor symptoms. Examining how partial dopamine depletion affects nigral regulation of cholinergic activity in an early-stage Parkinson's disease mouse model, revealed region-specific alterations in how remaining dopamine inputs regulate cholinergic excitability in the dorsomedial and dorsolateral striatum. Specifically, dopamine depletion downregulates metabotropic glutamate receptors on DLS ChIs, abolishing the ability of dopamine inputs to drive burst firing, leading to motor impairments in Parkinson's disease.
Article
Cell Biology
Core Baimel, Emil Jang, Samantha L. Scudder, Kasra Manocheri, Adam G. Carter
Summary: Cholinergic interneurons in the nucleus accumbens (NAc) are modulated by ventral hippocampus and paraventricular nucleus of the thalamus, with the former causing an inhibitory pause in firing. This inhibition is mediated by local parvalbumin interneurons and reflects fundamental differences in connectivity compared to the dorsal striatum.
Article
Clinical Neurology
Rodrigo Manuel Paz, Cecilia Tubert, Agostina Monica Stahl, Yimy Amarillo, Lorena Rela, Mario Gustavo Murer
Summary: Enhanced striatal cholinergic interneuron activity contributes to the striatal hypercholinergic state in Parkinson's disease and levodopa-induced dyskinesia. Dysregulation of D5-cAMP signaling and membrane ion channels in cholinergic interneurons causes aberrant burst-pause firing, which can be dampened by pharmacological intervention, providing a potential therapeutic target for alleviating parkinsonism and dyskinesia.
MOVEMENT DISORDERS
(2021)
Article
Multidisciplinary Sciences
Serena Becchi, Billy Chieng, Laura A. Bradfield, Roberto Capellan, Beatrice K. Leung, Bernard W. Balleine
Summary: The loss of neurons in the parafascicular thalamus and their inputs to dorsomedial striatum in Lewy body disease and Parkinson's disease dementia have been associated with neuroinflammation. The effects of this neuroinflammation on the function of striatal cholinergic interneurons and the encoding of action-outcome associations necessary for goal-directed action were investigated in rats. The study found that the neuroinflammation inhibited the activity of cholinergic interneurons and disrupted goal-directed control, but these effects could be rescued by administration of selegiline, which enhances the activity of adenosine triphosphatase in cholinergic interneurons.
Article
Clinical Neurology
Rodrigo Manuel Paz, Agostina Monica Stahl, Lorena Rela, Mario Gustavo Murer, Cecilia Tubert
Summary: This study unravels the mechanisms underlying the abnormal activity of striatal cholinergic interneurons (SCIN) in Parkinson's disease (PD) patients treated with levodopa, and suggests that pharmacological interventions can restore their normal function.
MOVEMENT DISORDERS
(2022)
Article
Neurosciences
Li-Jin Chen, Jeng-Rung Chen, Guo-Fang Tseng
Summary: Hydrocephalus alters neurotransmission pathways in the striatum, disrupting the balance between the basal ganglia circuits, which may contribute to motor impairments in hydrocephalus.
FLUIDS AND BARRIERS OF THE CNS
(2022)
Article
Cell Biology
Myoung Seok Ko, Ji Young Yun, In-Jeoung Baek, Jung Eun Jang, Jung Jin Hwang, Seung Eun Lee, Seung-Ho Heo, David A. Bader, Chul-Ho Lee, Jaeseok Han, Jong-Seok Moon, Jae Man Lee, Eun-Gyoung Hong, In-Kyu Lee, Seong Who Kim, Joong Yeol Park, Sean M. Hartig, Un Jung Kang, David D. Moore, Eun Hee Koh, Ki-up Lee
Summary: This study revealed the role of a specific gene, pink1, in mitochondrial autophagy, where its deficiency induces dysfunction in brown adipose tissue and obesity. Surprisingly, the induction of NLRP3 did not lead to canonical inflammasome activity, but instead caused brown adipocyte precursors to differentiate into white-like adipocytes. These findings suggest a new mitochondria-NLRP3 pathway that contributes to BAT dysfunction and provide potential therapeutic targets for obesity-related metabolic diseases.
Article
Neurosciences
Jeff A. Beeler, Devry Mourra, Roseanna M. Zanca, Abigail Kalmbach, Celia Gellman, Benjamin Y. Klein, Rebecca Ravenelle, Peter Serrano, Holly Moore, Stephen Rayport, Susana Mingote, Nesha S. Burghardt
Summary: The rodent model of anorexia nervosa shows distinct resilient and vulnerable phenotypes, with dopamine playing a central role in modulating susceptibility.
BIOLOGICAL PSYCHIATRY
(2021)
Article
Clinical Neurology
Christina D. Orru, Thong C. Ma, Andrew G. Hughson, Bradley R. Groveman, Ankit Srivastava, Douglas Galasko, Rachel Angers, Patrick Downey, Karen Crawford, Samantha J. Hutten, Un Jung Kang, Byron Caughey
Summary: The study shows that an improved assay for diagnosing Parkinson's disease dramatically reduces the diagnosis time while maintaining high performance standards. Positive signals were found in 97% of Parkinson's disease cases compared to only 13% of healthy controls, with weak correlations between assay parameters and clinical measures observed. The assay's efficiency in diagnosing Parkinson's disease is supported by these findings.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Editorial Material
Neurosciences
Bastiaan R. Bloem, Claudia Trenkwalder, Alvaro Sanchez-Ferro, Lorraine V. Kalia, Roy Alcalay, Han-Lin Chiang, Un Jung Kang, Christopher Goetz, Patrik Brundin, Stella M. Papa
Summary: Despite concerns raised by people with Parkinson's disease (PD) and their physicians regarding the efficacy and safety of COVID-19 vaccines in the specific context of PD and its treatment, current literature and experience with widespread vaccination suggest that COVID-19 vaccination with approved vaccines is recommended for PD patients, unless there is a specific contraindication.
JOURNAL OF PARKINSONS DISEASE
(2021)
Article
Clinical Neurology
Suman Dutta, Simon Hornung, Adira Kruayatidee, Katherine N. Maina, Irish del Rosario, Kimberly C. Paul, Darice Y. Wong, Aline Duarte Folle, Daniela Markovic, Jose-Alberto Palma, Geidy E. Serrano, Charles H. Adler, Susan L. Perlman, Wayne W. Poon, Un Jung Kang, Roy N. Alcalay, Miriam Sklerov, Karen H. Gylys, Horacio Kaufmann, Brent L. Fogel, Jeff M. Bronstein, Beate Ritz, Gal Bitan
Summary: The study found that measuring α-syn in exosomes from blood can effectively distinguish between patients with PD and MSA with high sensitivity and specificity. A multinomial logistic model combining α-syn concentration, exosome concentration, and a ratio between α-syn concentrations in specific exosomes showed promising results in separating PD from MSA.
ACTA NEUROPATHOLOGICA
(2021)
Review
Neurosciences
Daniel Eskenazi, Lauren Malave, Susana Mingote, Leora Yetnikoff, Samira Ztaou, Vlad Velicu, Stephen Rayport, Nao Chuhma
Summary: Dopamine neurons have the ability to cotransmit glutamate, playing significant roles in neuroprotection, behavioral responses, and neuropsychiatric disorders.
FRONTIERS IN NEURAL CIRCUITS
(2021)
Review
Behavioral Sciences
Marianne Amalric, Tommy Pattij, Ioannis Sotiropoulos, Joana M. Silva, Nuno Sousa, Samira Ztaou, Cristiano Chiamulera, Lars U. Wahlberg, Dwaine F. Emerich, Giovanna Paolone
Summary: Historically, studies on neurodegenerative diseases have largely examined alterations in specific neuronal populations, but it is becoming increasingly clear that the integrity of multiple interconnected neuronal circuits regulates various brain activities in mammals. The dopaminergic and cholinergic systems play crucial roles in orchestrating cognitive and non-cognitive symptoms in PD and AD.
FRONTIERS IN BEHAVIORAL NEUROSCIENCE
(2021)
Article
Neurosciences
Samira Ztaou, Soo Jung Oh, Sophia Tepler, Sixtine Fleury, Miriam Matamales, Jesus Bertran-Gonzalez, Nao Chuhma, Stephen Rayport
Summary: This study demonstrates that a single dose of amphetamine has delayed regionally heterogeneous effects on cholinergic interneuron activity, which likely involves extra-striatal synaptic input.
Article
Clinical Neurology
Jose-Alberto Palma, Jose Martinez, Patricio Millar Vernetti, Thong Ma, Miguel A. Perez, Judy Zhong, Yingzhi Qian, Suman Dutta, Katherine N. Maina, Ibrar Siddique, Gal Bitan, Benjamin Ades-Aron, Timothy M. Shepherd, Un J. Kang, Horacio Kaufmann
Summary: The efficacy and safety of sirolimus in patients with multiple system atrophy (MSA) were investigated in this study. The results showed that sirolimus treatment for 48 weeks was futile in slowing the progression of MSA and had no effect on biomarkers compared to placebo. Changes in blood neurofilament light chain (NfL) and whole brain atrophy were identified as promising biomarkers of disease progression for future clinical trials.
MOVEMENT DISORDERS
(2022)
Article
Cell Biology
Milagros Pereira Luppi, Maite Azcorra, Giuliana Caronia-Brown, Jean-Francois Poulin, Zachary Gaertner, Serafin Gatica, Oscar Andres Moreno-Ramos, Navid Nouri, Marilyn Dubois, Yongchao C. Ma, Charu Ramakrishnan, Lief Fenno, Yoon Seok Kim, Karl Deisseroth, Francesca Cicchetti, Daniel A. Dombeck, Rajeshwar Awatramani
Summary: The study found that Sox6 expression distinguishes ventrally and dorsally biased dopamine (DA) neuron populations in the substantia nigra pars compacta (SNc), showing distinct molecular profiles, projections, and functions. This adult division was encoded early in development.
Editorial Material
Neurosciences
Jean-Francois Poulin, Talia Newcombe Lerner, Mark W. Howe
FRONTIERS IN NEURAL CIRCUITS
(2022)
Article
Neurosciences
Giulietta Maria Riboldi, Marco J. Russo, Ling Pan, Kristen Watkins, Un Jung Kang
Summary: Non-motor symptoms like dysautonomia and REM sleep behavior disorder in Parkinson's disease may indicate different types of the disease. Through analysis of data from newly diagnosed Parkinson's patients, it was found that dysautonomia symptoms can predict disease progression more accurately.
NPJ PARKINSONS DISEASE
(2022)
Correction
Neurosciences
Giulietta Maria Riboldi, Marco J. Russo, Ling Pan, Kristen Watkins, Un Jung Kang
NPJ PARKINSONS DISEASE
(2023)
Article
Clinical Neurology
Yong Hu, Thong C. Ma, Stephanie L. Alberico, Yunmin Ding, Lingjing Jin, Un Jung Kang
Summary: This study aimed to determine whether direct modulation of SNr GABAergic neurons and SNr projections to the PPN can regulate PD symptoms and levodopa-induced dyskinesia (LID). The results showed that suppressing SNr neuron activity improved akinesia, while increasing SNr neuronal activity significantly reduced LID. The projections from SNr to PPN likely mediate the antidyskinetic effect of increasing SNr neuronal activity.
MOVEMENT DISORDERS
(2023)