Trans-synaptic modulation of cholinergic circuits tunes opioid reinforcement DOI Creative Commons
Stefano Zucca, Gloria Brunori, Henry A. Dunn

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2025, Volume and Issue: 122(12)

Published: March 20, 2025

Opioids trigger structural and functional neural adaptations of the reward circuit that lead to dependence. Synaptic cell adhesion molecules (CAMs) play a pivotal role in organization present prime candidates for orchestrating remodeling connections response drug exposure. However, contribution CAMs opioid-induced rewiring has not been explored. Here, we used unbiased molecular profiling identify nucleus accumbens (NAc) modulated by morphine administration. We found opioid exposure induces expression ELFN1, CAM selectively expressed cholinergic interneurons NAc. determined ELFN1 acts trans-synaptically modulate strength plasticity glutamatergic inputs onto neurons via recruitment presynaptic metabotropic glutamate receptor 4 (mGlu4). Disruption Elfn1 diminished intake self-administering mice. Together, our findings key factor responsible adjusting effects modulating configuration striatal circuitry an experience-dependent fashion unveil potential therapeutic target combating abuse.

Language: Английский

Synaptic deregulation of cholinergic projection neurons causes olfactory dysfunction across 5 fly Parkinsonism models DOI Open Access
Ulrike Pech, Jasper Janssens, Nils Schoovaerts

et al.

Published: July 17, 2024

The classical diagnosis of Parkinsonism is based on motor symptoms that are the consequence nigrostriatal pathway dysfunction and reduced dopaminergic output. However, a decade prior to emergence issues, patients frequently experience non-motor symptoms, such as sense smell (hyposmia). cellular molecular bases for these early defects remain enigmatic. To explore this, we developed new collection five fruit fly models representing various forms familial conducted single-cell RNA sequencing young entire brains models. Interestingly, cholinergic projection neurons most vulnerable cells genes associated with presynaptic function deregulated. Additional single nucleus three specific brain regions Parkinson’s disease recapitulates finding. Indeed, disturbances lead synaptic dysfunction, notably affecting olfactory crucial in flies. Our research uncovers one earliest indicators 5 different higher-order neurons, it suggests common pathways contribute development hyposmia.

Language: Английский

Citations

7
Compartmental function and modulation of the striatum DOI
Eric M. Prager, Joshua L. Plotkin

Journal of Neuroscience Research, Journal Year: 2019, Volume and Issue: 97(12), P. 1503 - 1514

Published: Sept. 5, 2019

The striatum plays a central role in guiding numerous complex behaviors, ranging from motor control to action selection and reward learning. diverse responsibilities of the are reflected by complexity its organization. In this review, we will summarize what is currently known about compartmental layout striatum, an organizational principle that crucial for allowing guide such array behaviors. We focus on anatomical functional properties striosome (patch) matrix compartments how engagement these uniquely controlled their afferents, intrinsic properties, neuromodulation. give examples advances technology have opened door functionally dissecting striatum's design, close offering thoughts future relevance human disease.

Language: Английский

Citations

53
Cholinergic dysfunction in the dorsal striatum promotes habit formation and maladaptive eating DOI Open Access
M. Favier, Helena Janíčková,

Damián Justo

et al.

Journal of Clinical Investigation, Journal Year: 2020, Volume and Issue: 130(12), P. 6616 - 6630

Published: Nov. 8, 2020

Dysregulation of habit formation has been recently proposed as pivotal to eating disorders. Here, we report that a subset patients suffering from restrictive anorexia nervosa have enhanced compared with healthy controls. Habit is modulated by striatal cholinergic interneurons. These interneurons express vesicular transporters for acetylcholine (VAChT) and glutamate (VGLUT3) use acetylcholine/glutamate cotransmission regulate functions. Using mice genetically silenced VAChT (VAChT conditional KO, VAChTcKO) or VGLUT3 (VGLUT3cKO), investigated the roles released play in maladaptive eating. Silencing favored goal-directed behaviors had no impact on behavior. In contrast, VAChTcKO were more prone habits Specific deletion dorsomedial striatum adult was sufficient phenocopy mice. Interestingly, reduced dopamine release but not dorsolateral striatum. The dysfunctional behavior alleviated donepezil l-DOPA, confirming an acetylcholine/dopamine deficit. Our study reveals loss leads imbalance compartments, thereby promoting vulnerability

Language: Английский

Citations

46
Role of α6-Nicotinic Receptors in Alcohol-Induced GABAergic Synaptic Transmission and Plasticity to Cholinergic Interneurons in the Nucleus Accumbens DOI
Hillary A. Wadsworth,

Elizabeth Q. Anderson,

Benjamin M. Williams

et al.

Molecular Neurobiology, Journal Year: 2023, Volume and Issue: 60(6), P. 3113 - 3129

Published: Feb. 18, 2023

Language: Английский

Citations

15
M1/M4 receptors as potential therapeutic treatments for schizophrenia: A comprehensive study DOI

Lingsheng Fu,

Yi Luo,

Longyan Niu

et al.

Bioorganic & Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 105, P. 117728 - 117728

Published: April 16, 2024

Language: Английский

Citations

5
Targeting the Actions of Muscarinic Receptors on Dopamine Systems: New Strategies for Treating Neuropsychiatric Disorders DOI Creative Commons
Eric J. Nunes, Nii Addy, P. Jeffrey Conn

et al.

The Annual Review of Pharmacology and Toxicology, Journal Year: 2023, Volume and Issue: 64(1), P. 277 - 289

Published: Aug. 8, 2023

Cholinergic regulation of dopamine (DA) signaling has significant implications for numerous disorders, including schizophrenia, substance use and mood-related disorders. The activity midbrain DA neurons release patterns in terminal regions are tightly regulated by cholinergic found both the striatum hindbrain. These can modulate circuitry activating receptors, muscarinic acetylcholine receptor (mAChR) subtypes. This review specifically focuses on complex role M2, M4, M5 mAChR subtypes regulating neuron potential clinical targeting these

Language: Английский

Citations

13
Dopamine-sensitive neurons in the mesencephalic locomotor region control locomotion initiation, stop, and turns DOI Creative Commons

Andrea Juárez Tello,

Cornelis Immanuel van der Zouwen, Léonie Dejas

et al.

Cell Reports, Journal Year: 2024, Volume and Issue: 43(5), P. 114187 - 114187

Published: May 1, 2024

The locomotor role of dopaminergic neurons is traditionally attributed to their ascending projections the basal ganglia, which project mesencephalic region (MLR). In addition, descending MLR are present from vertebrates mammals. However, targeted in and behavioral unknown Here, we identify genetically defined cells that express D

Language: Английский

Citations

4
Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes DOI Creative Commons
Jeffrey Stedehouder, Bradley M. Roberts, Shinil Raina

et al.

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

Published: Nov. 19, 2024

Abstract Astrocytes are increasingly appreciated to possess underestimated and important roles in modulating neuronal circuits. striatum can regulate dopamine transmission by governing the extracellular tone of axonal neuromodulators, including GABA adenosine. However, here we reveal that striatal astrocytes occupy a cell type-specific anatomical functional relationship with cholinergic interneurons (ChIs), through which they rapidly excite ChIs govern release via nicotinic acetylcholine receptors on subsecond timescales. We identify ChI somata unexpectedly close proximity astrocyte somata, mouse human, forming “soma-to-soma” satellite-like configuration not typically observed for other neurons. find transient depolarization reversibly regulates excitability decreasing calcium. These findings privileged satellite astrocyte-interneuron interaction operating timescales regulation calcium dynamics shape downstream circuit activity signaling.

Language: Английский

Citations

4
Trihexyphenidyl rescues the deficit in dopamine neurotransmission in a mouse model of DYT1 dystonia DOI Creative Commons
Anthony M. Downs,

Xueliang Fan,

Christine Donsante

et al.

Neurobiology of Disease, Journal Year: 2019, Volume and Issue: 125, P. 115 - 122

Published: Jan. 30, 2019

Language: Английский

Citations

33
The neurobiological basis for novel experimental therapeutics in dystonia DOI Creative Commons
Anthony M. Downs,

Kaitlyn M. Roman,

Simone A. Campbell

et al.

Neurobiology of Disease, Journal Year: 2019, Volume and Issue: 130, P. 104526 - 104526

Published: July 4, 2019

Language: Английский

Citations

32