The Hidden Life of the Basal Ganglia DOI Open Access
Hagai Bergman

The MIT Press eBooks, Journal Year: 2021, Volume and Issue: unknown

Published: Oct. 12, 2021

The anatomy and physiology of the basal ganglia their relation to brain behavior, disorders therapies, philosophy mind moral values. main task ganglia—a group subcortical nuclei, located at base brain—is optimize execute our automatic behavior. In this book, Hagai Bergman analyzes ganglia, discussing even Drawing on his forty years studying presents new information computational models, Parkinson's disease other ganglia-related disorders, such therapies as deep stimulation. Focusing studies nonhuman primates human relying system in vivo extra-cellular recording techniques, first describes major structures that constitute morphology cellular elements, synaptic connectivity physiological function health disease. He discusses healthy describing four generations then traces ganglia–related treatments, including its pharmacological surgical therapies. Finally, considers implications these findings for concerns free will. Explaining leap into domains rarely explored neuroscientific accounts, writes longer he more is convinced they are truly both mind.

Language: Английский

Muscarinic acetylcholine receptors for psychotic disorders: bench-side to clinic DOI Creative Commons
Samantha E. Yohn, Peter J. Weiden, Christian C. Felder

et al.

Trends in Pharmacological Sciences, Journal Year: 2022, Volume and Issue: 43(12), P. 1098 - 1112

Published: Oct. 20, 2022

Modern interest in muscarinic acetylcholine receptor (mAChR) activators for schizophrenia began the 1990s when xanomeline, an M1/M4-preferring mAChR agonist developed cognitive symptoms of Alzheimer's disease (AD), had unexpected antipsychotic activity. However, strategies to address tolerability concerns associated with activation peripheral mAChRs were not available at that time. The discovery specific targeted ligands and combination treatments reduce engagement have advanced potential as effective psychotic disorders. This review provides perspectives on background identification antipsychotics, advances preclinical understanding targets, current state under active clinical development schizophrenia.

Language: Английский

Citations

65
Targeted activation of midbrain neurons restores locomotor function in mouse models of parkinsonism DOI Creative Commons
Débora Masini, Ole Kiehn

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 26, 2022

Abstract The pedunculopontine nucleus (PPN) is a locomotor command area containing glutamatergic neurons that control initiation and maintenance. These motor actions are deficient in Parkinson’s disease (PD), where dopaminergic neurodegeneration alters basal ganglia activity. Being downstream of the ganglia, PPN may be suitable target for ameliorating parkinsonian symptoms. Here, we use vivo cell-type specific activation to restore function two mouse models parkinsonism made by acute pharmacological blockage dopamine transmission. With combination chemo- opto-genetics, show excitation caudal can normalize otherwise severe deficit PD, whereas targeting local GABAergic population only leads recovery slow locomotion. rescue driven independent activity nearby promoting Cuneiform neurons. Our observations point as potential neuromodulatory restoration PD.

Language: Английский

Citations

55
Deep brain stimulation alleviates tics in Tourette syndrome via striatal dopamine transmission DOI Creative Commons
Aaron E. Rusheen, Juan M. Rojas Cabrera, Abhinav Goyal

et al.

Brain, Journal Year: 2023, Volume and Issue: 146(10), P. 4174 - 4190

Published: May 4, 2023

Abstract Tourette syndrome is a childhood-onset neuropsychiatric disorder characterized by intrusive motor and vocal tics that can lead to self-injury deleterious mental health complications. While dysfunction in striatal dopamine neurotransmission has been proposed underlie tic behaviour, evidence scarce inconclusive. Deep brain stimulation (DBS) of the thalamic centromedian parafascicular complex (CMPf), an approved surgical interventive treatment for medical refractory syndrome, may reduce affecting release. Here, we use electrophysiology, electrochemistry, optogenetics, pharmacological treatments behavioural measurements mechanistically examine how DBS modulates synaptic tonic activity dorsomedial striatum. Previous studies demonstrated focal disruption GABAergic transmission dorsolateral striatum rats led repetitive recapitulating major symptom syndrome. We employed this model under light anaesthesia found CMPf evoked release elevated levels via cholinergic interneurons while concomitantly reducing behaviour. The improvement behaviour was be mediated D2 receptor activation as blocking prevented therapeutic response. Our results demonstrate mediates effects points driver pathoneurophysiology

Language: Английский

Citations

23
Targeted Activation of Cholinergic Interneurons Accounts for the Modulation of Dopamine by Striatal Nicotinic Receptors DOI Creative Commons
Katherine R. Brimblecombe, Sarah Threlfell, Daniel Dautan

et al.

eNeuro, Journal Year: 2018, Volume and Issue: 5(5), P. ENEURO.0397 - 17.2018

Published: Sept. 1, 2018

Striatal dopamine (DA) is a major player in action selection and reinforcement. DA release under strong local control by striatal ACh acting at axonal nicotinic receptors (nAChRs) on axons. nAChRs have been shown to how released response ascending activity from neurons, they also directly drive following synchronized small cholinergic network. The source of has thought arise solely intrinsic interneurons (ChIs), but recent findings identified inputs striatum brainstem nuclei, the pedunculopontine nucleus (PPN) laterodorsal tegmentum (LDT). Here, we used targeted optogenetic activation alongside detection with fast-scan cyclic voltammetry test whether ChIs alone and/or afferents can account for drives modulates rat striatum. We demonstrate that transient light release, corroborating extending previous observations mouse rat. However, same stimulation did not nor it modulate activated subsequently electrical stimulation, whereas so. were unable obtain any evidence modulation PPN/LDT stimulation. By contrast, could readily identify are sufficient provide powerfully regulates via nAChRs.

Language: Английский

Citations

71
Striatal cholinergic transmission. Focus on nicotinic receptors’ influence in striatal circuits DOI
Maxime Assous

European Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 53(8), P. 2421 - 2442

Published: Feb. 5, 2021

Abstract The critical role of acetylcholine (ACh) in the basal ganglia is evident from effect cholinergic agents patients suffering several related neurological disorders, such as Parkinson's disease, Tourette syndrome, or dystonia. striatum possesses highest density ACh markers underlying importance this structure. Striatal interneurons (CINs) are responsible for bulk striatal ACh, although extrinsic afferents brainstem structures may also play a role. CINs tonically active, and synchronized pause their activity occurs following presentation salient stimuli during behavioral conditioning. However, synaptic mechanisms involved not fully understood physiological response. modulates circuits by acting on muscarinic nicotinic receptors existing combinations both presynaptically postsynaptically. While effects through have received particular attention, function has been less studied. Here, after briefly reviewing relevant results regarding expression function, I will focus receptor expressed glutamatergic dopaminergic postsynaptically diverse populations. review recent evidence suggesting involvement different GABAergic sources two distinct nicotinic‐receptor‐mediated circuits: disynaptic inhibition projection neurons recurrent among CINs. A better understanding help to develop targeted pharmacological interventions treat brain disorders dystonia, nicotine addiction.

Language: Английский

Citations

43
Local regulation of striatal dopamine: A diversity of circuit mechanisms for a diversity of behavioral functions? DOI
Elizabeth N. Holly, Jamie Galanaugh, Marc V. Fuccillo

et al.

Current Opinion in Neurobiology, Journal Year: 2024, Volume and Issue: 85, P. 102839 - 102839

Published: Feb. 3, 2024

Language: Английский

Citations

7
A mismatch between striatal cholinergic pauses and dopaminergic reward prediction errors DOI Creative Commons
Mariana Duhne, Ali Mohebi,

Kyoungjun Kim

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(41)

Published: Oct. 4, 2024

Striatal acetylcholine and dopamine critically regulate movement, motivation, reward-related learning. Pauses in cholinergic interneuron (CIN) firing are thought to coincide with pulses encoding reward prediction errors (RPE) jointly enable synaptic plasticity. Here, we examine the of identified CINs during reward-guided decision-making freely moving rats compare this release. Relationships between CINs, dopamine, behavior varied strongly by subregion. In dorsal–lateral striatum, a Go! cue evoked burst–pause CIN spiking, followed brief pulse that was unrelated RPE. dorsal–medial only pause, curtailed movement-selective rebound firing. Finally, ventral RPE-coding increases both firing, without consistent pause. Our results demonstrate spatial temporal dissociation pauses RPE signals will inform future models striatal information processing under normal pathological conditions.

Language: Английский

Citations

7
Pedunculopontine Glutamatergic Neurons Provide a Novel Source of Feedforward Inhibition in the Striatum by Selectively Targeting Interneurons DOI Open Access
Maxime Assous, Daniel Dautan, James M. Tepper

et al.

Journal of Neuroscience, Journal Year: 2019, Volume and Issue: 39(24), P. 4727 - 4737

Published: April 5, 2019

The main excitatory inputs to the striatum arising from cortex and thalamus innervate both striatal spiny projection neurons interneurons. These glutamatergic GABAergic interneurons have been suggested regulate spike timing of via feedforward inhibition. Understanding how different are integrated within circuitry they output is crucial for understanding basal ganglia function related behaviors. Here, using VGLUT2 mice sexes, we report existence a mesencephalic locomotor region that avoids selectively innervates Specifically, optogenetic activation axons pedunculopontine nucleus induced monosynaptic excitation in most recorded cholinergic fast-spiking Optogenetic stimulation awake head-fixed consistently an increase firing rate putative In contrast, this did not induce responses but rather disynaptic inhibitory

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 laterodorsal tegmentum projections to nucleus accumbens in reward-related behaviors DOI Creative Commons
Bárbara Coimbra, Carina Soares‐Cunha, Nivaldo A. P. de Vasconcelos

et al.

Nature Communications, Journal Year: 2019, Volume and Issue: 10(1)

Published: Sept. 12, 2019

The laterodorsal tegmentum (LDT) is associated with reward considering that it modulates VTA neuronal activity, but recent anatomical evidence shows the LDT also directly projects to nucleus accumbens (NAc). We show majority of LDT-NAc inputs are cholinergic, there GABAergic and glutamatergic innervation; activation induces a predominantly excitatory response in NAc. Non-selective optogenetic projections rats enhances motivational drive shifts preference an otherwise equal reward; whereas inhibition these opposite. Activation robust place preference. In mice, specific cholinergic (but not or GABAergic) sufficient shift preference, increase motivation, positive reinforcement different behavioral paradigms. These results provide play important role motivated behaviors reinforcement, distinct populations differentially contribute for behaviors.

Language: Английский

Citations

45