Striosomes Mediate Value-Based Learning Vulnerable in Age and a Huntington’s Disease Model

Cell, Journal Year: 2020, Volume and Issue: 183(4), P. 918 - 934.e49

Published: Oct. 27, 2020

Language: Английский

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Function and Regulation of ALDH1A1-Positive Nigrostriatal Dopaminergic Neurons in Motor Control and Parkinson’s Disease

Frontiers in Neural Circuits, Journal Year: 2021, Volume and Issue: 15

Published: May 17, 2021

Dopamine is an important chemical messenger in the brain, which modulates movement, reward, motivation, and memory. Different populations of neurons can produce release dopamine brain regulate different behaviors. Here we focus our discussion on a small but distinct group dopamine-producing neurons, display most profound loss ventral

Language: Английский

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Multiplexed action-outcome representation by striatal striosome-matrix compartments detected with a mouse cost-benefit foraging task

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

Published: March 22, 2022

Abstract Learning about positive and negative outcomes of actions is crucial for survival underpinned by conserved circuits including the striatum. How associations between are formed not fully understood, particularly when have mixed features. We developed a novel foraging (‘bandit’) task requiring mice to maximize rewards while minimizing punishments. By 2-photon Ca ++ imaging, we monitored activity visually identified anterodorsal striatal striosomal matrix neurons. found that action-outcome reward punishment were encoded in parallel partially overlapping populations. Single neurons could, one action, encode opposing valence. Striosome compartments consistently exhibited stronger representations reinforcement than matrix, especially high or prediction errors. These findings demonstrate multiplexing contingencies single suggest important learning.

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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Striatal Direct Pathway Targets Npas1⁺Pallidal Neurons

Journal of Neuroscience, Journal Year: 2021, Volume and Issue: 41(18), P. 3966 - 3987

Published: March 17, 2021

The classic basal ganglia circuit model asserts a complete segregation of the two striatal output pathways. Empirical data argue that, in addition to indirect-pathway projection neurons (iSPNs), direct-pathway (dSPNs) innervate external globus pallidus (GPe). However, functions latter were not known. In this study, we interrogated organization principles striatopallidal projections and their roles full-body movement mice (both males females). contrast canonical motor-promoting response dSPNs dorsomedial striatum ( DMS dSPNs), optogenetic stimulation dorsolateral DLS dSPNs) suppressed locomotion. Circuit analyses revealed that selectively target Npas1 + GPe. chronic 6-hydroxydopamine lesion Parkinson's disease, dSPN-Npas1 was dramatically strengthened. As suppresses movement, enhancement represents mechanism for hypokinetic symptoms disease has been previously considered. sum, our results suggest dSPN input GPe is critical component involved regulation both healthy parkinsonian states. SIGNIFICANCE STATEMENT model, described as divergent structure: it controls motor adaptive through segregated, opposing streams. experimental show from pallidum have largely ignored. Here, showed subpathway targets select subset motor-suppressing. We found undergoes changes model. particular, increase strength contributes slowness or reduced movements observed disease.

Language: Английский

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Molecular heterogeneity in the substantia nigra: A roadmap for understanding PD motor pathophysiology

Neurobiology of Disease, Journal Year: 2022, Volume and Issue: 175, P. 105925 - 105925

Published: Nov. 11, 2022

As the ability to capture single-cell expression profiles has grown in recent years, neuroscientists studying a wide gamut of brain regions have discovered remarkable heterogeneity within seemingly related populations (Saunders et al., 2018a; Zeisel 2015). These "molecular subtypes" been demonstrated even nuclei expressing same neurotransmitter Poulin 2020; Ren 2019; Okaty 2020). Recently, dopamine (DA) neurons substantia nigra pars compacta (SNc) and adjacent ventral tegmental area (VTA) revealed be diverse not only when comparing between these two dopaminergic nuclei, but them, with distribution identified subtypes often agnostic traditional neuroanatomical boundaries Hook 2018; Kramer La Manno 2016; 2014; Tiklova 2018). Such molecularly defined subpopulations subject several studies. Investigations ultimately unveiled many distinctive properties across domains, such as their axonal projections functional (Poulin Wu Pereira Luppi 2021; Evans 2017; key differences begun corroborate biological relevance DA neuron taxonomic schemes. We hypothesize that putative molecular subtypes, circuits, could shed light on variety dopamine-related symptoms observed diseases including depression, chronic pain, addiction, Parkinson's Disease. While it is difficult reconcile how single can involved so unrelated phenotypes, one solution existence individual pathways serving different functions, distinct nodes for pathways. Indeed, this conceptual framework already dogma anatomically pathways, mesocortical, mesolimbic mesostriatal (Bjorklund & Dunnett, 2007). Here, we discuss our existing knowledge attempt provide roadmap novel insights into motor disease (PD) (Fig. 1A). By exploring correlating relative degeneration SNc, may gain deeper understanding cell-intrinsic mechanisms underlying why some degenerate more than others PD. Similarly, by mapping inputs, projections, functions better understand roles circuit-level dysfunction diseases.

Language: Английский

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Comparing tonic and phasic dendritic calcium in cholinergic pedunculopontine neurons and dopaminergic substantia nigra neurons

European Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 59(7), P. 1638 - 1656

Published: Feb. 21, 2024

Abstract Several brainstem nuclei degenerate in Parkinson's disease (PD). In addition to the well‐characterized dopaminergic neurons of substantia nigra pars compacta (SNc), cholinergic pedunculopontine nucleus (PPN) also PD. One leading hypothesis selective vulnerability is that pacemaking activity and activation low‐threshold L‐type calcium current are major contributors tonic load cellular stress SNc neurons. However, it not yet clear whether vulnerable PPN share this property. Therefore, we used two‐photon dendritic imaging whole‐cell electrophysiology evaluate role channels phasic signals addition, investigated N‐ P/Q‐type channel regulation firing properties We found blocking reduces rate levels By contrast, did depend on L‐, or channels. either (with nifedipine) omega‐conotoxin MVIIC) influx dendrites. Together, these findings show play different roles neurons, suggest responsible for therefore likely be a source cells.

Language: Английский

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Striosomes Target Nigral Dopamine-Containing Neurons via Direct-D1 and Indirect-D2 Pathways Paralleling Classic Direct-Indirect Basal Ganglia Systems

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 1, 2024

Balanced activity of canonical direct D1 and indirect D2 basal ganglia pathways is considered a core requirement for normal movement, their imbalance an etiologic factor in movement neuropsychiatric disorders. We present evidence conceptually equivalent pair direct-D1 indirect-D2 that arise from striatal projection neurons (SPNs) the striosome compartment rather than SPNs matrix, as do pathways. These S-D1 S-D2 striosomal target substantia nigra dopamine-containing instead motor output nuclei. They modulate oppositely to modulation by pathways: inhibitory excitatory. The circuits likely influence motivation learning action, complementing reorienting pathway modulation. A major conceptual reformulation classic direct-indirect model function needed, well reconsideration effects D2-targeting therapeutic drugs.

Language: Английский

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Calbindin and Girk2/Aldh1a1 define resilient vs vulnerable dopaminergic neurons in a primate Parkinson’s disease model

npj Parkinson s Disease, Journal Year: 2024, Volume and Issue: 10(1)

Published: Sept. 2, 2024

The differential vulnerability of dopaminergic neurons the substantia nigra pars compacta (SNc) is a critical and unresolved question in Parkinson´s disease. Studies mice show diverse susceptibility subpopulations nigral to various toxic agents. In primate midbrain, molecular phenotypes their are poorly characterized. We performed detailed histological study determine anatomical distribution different within identified midbrain selective control MPTP-treated monkeys. ventral tier SNc (nigrosome), rich Aldh1a1 Girk2 intermingled, whereas calbindin marker that best identifies most resilient located dorsal tegmental area, recapitulating well-defined dorsoventral axis degeneration neurons. particular, loss Aldh1a1+ was observed parallel progressive development parkinsonism. were main population vulnerable nigrostriatal-projecting neurons, while Aldh1a1- giving rise nigropallidal projections remained relatively preserved. Moreover, bundles entwined dendrites with long trajectories extending towards reticulata emerged from clusters colocalized dense cannabinoid receptor 1 afferent fibers likely representing part striatonigral projection affected human disorders, including conclusion, can be by using Girk2. Further studies needed define afferent/efferent patterns these

Language: Английский

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Diverse midbrain dopaminergic neuron subtypes and implications for complex clinical symptoms of Parkinson’s disease

Ageing and Neurodegenerative Diseases, Journal Year: 2021, Volume and Issue: unknown

Published: Jan. 1, 2021

Ageing and Neurodegenerative Diseases is an open access multidisciplinary journal, focusing on innovative research advances in the cellular molecular mechanisms underlying ageing process age-related neurodegenerative diseases, such as Alzheimer's disease, Parkinson's amyotrophic lateral sclerosis, etc., therapeutic interventions this field.

Language: Английский

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