Context-Dependent Multiplexing by Individual VTA Dopamine Neurons DOI Open Access
Yves Kremer, Jérôme Flakowski,

Clément Rohner

и другие.

Journal of Neuroscience, Год журнала: 2020, Номер 40(39), С. 7489 - 7509

Опубликована: Авг. 28, 2020

Dopamine (DA) neurons of the VTA track cues and rewards to generate a reward prediction error signal during Pavlovian conditioning. Here we explored how these respond self-paced, operant task in freely moving mice. The animal could trigger reward-predicting cue by remaining specific location an box for brief time before spout collection. DA were identified using DAT-Cre male mice that carried optrode with minimal impact on behavioral task. In vivo single-unit recordings revealed transient fast spiking responses correct trials, while incorrect ones activity paused, reflecting positive negative signals prediction. In parallel, majority simultaneously encoded multiple actions (e.g., movement velocity, acceleration, distance goal, licking) sustained slow firing modulation. Applying GLM, show such multiplexed encoding rewarding motor variables individual was only apparent mouse engaged Downstream targets may exploit goal-directed multiplexing adjust optimize task9s outcome. SIGNIFICANCE STATEMENT code functions, including but also motivation locomotion. about half recorded perform multiplexing: they phasic tonic modes encode, respectively, cue/reward parameters, most prominently when engages self-paced operand non-DA neurons, contrast, encode parameters regardless engagement.

Язык: Английский

Connecting Circuits for Supraspinal Control of Locomotion DOI Creative Commons
Manuel J. Ferreira‐Pinto,

Ludwig Ruder,

Paolo Capelli

и другие.

Neuron, Год журнала: 2018, Номер 100(2), С. 361 - 374

Опубликована: Окт. 1, 2018

Язык: Английский

Процитировано

132
Dopamine and the Brainstem Locomotor Networks: From Lamprey to Human DOI Creative Commons
Dimitri Ryczko, Réjean Dubuc

Frontiers in Neuroscience, Год журнала: 2017, Номер 11

Опубликована: Май 26, 2017

In vertebrates, dopamine neurons are classically known to modulate locomotion via their ascending projections the basal ganglia that project brainstem locomotor networks. An increased dopaminergic tone is associated with increase in activity. pathological conditions where cells lost, such as Parkinson's disease, deficits traditionally reduced input ganglia. However, a descending pathway originating from substantia nigra pars compacta was recently discovered. It innervates mesencephalic region (MLR) vertebrates mammals. This shown output lampreys, and could very well play an important role Here, we provide detailed account on newly found lamprey, salamander, rat, monkey, man. lampreys salamanders, release MLR activation of reticulospinal carry command spinal cord. Dopamine potentiates through D1-receptor mechanism lampreys. rats, stimulation elicited pedunculopontine nucleus, part MLR. monkey model innervation networks reported. Dopaminergic fibers also present human nucleus. We discuss conserved this lamprey mammals, hypothesis reported disease.

Язык: Английский

Процитировано

116
Neural circuits and nicotinic acetylcholine receptors mediate the cholinergic regulation of midbrain dopaminergic neurons and nicotine dependence DOI Creative Commons
Cheng Xiao,

Chunyi Zhou,

Jinhong Jiang

и другие.

Acta Pharmacologica Sinica, Год журнала: 2019, Номер 41(1), С. 1 - 9

Опубликована: Сен. 25, 2019

Abstract Midbrain dopaminergic (DA) neurons are governed by an endogenous cholinergic system, originated in the mesopontine nuclei. Nicotine hijacks nicotinic acetylcholine receptors (nAChRs) and interferes with physiological function of system. In this review, we describe anatomical organization system key nAChR subtypes mediating regulation DA transmission nicotine reward dependence, effort to identify potential targets for smoking intervention. Cholinergic modulation midbrain systems relies on topographic projections, activation nAChRs neurons. Previous studies have revealed that α4, α6, β2 subunit-containing expressed their terminals striatum regulate firings activity-dependent dopamine release striatum. These undergo modification upon chronic exposure. Clinical investigation has demonstrated partial agonists these elevate success rate cessation relative placebo. However, further investigations required refine drug mitigate unpleasant side-effects.

Язык: Английский

Процитировано

90
Temporally restricted dopaminergic control of reward-conditioned movements DOI
Kwang Lee, Leslie D. Claar, Ayaka Hachisuka

и другие.

Nature Neuroscience, Год журнала: 2020, Номер 23(2), С. 209 - 216

Опубликована: Янв. 13, 2020

Язык: Английский

Процитировано

78
Modulation of motor behavior by the mesencephalic locomotor region DOI Creative Commons
Daniel Dautan,

Adrienn Kovács,

Tsogbadrakh Bayasgalan

и другие.

Cell Reports, Год журнала: 2021, Номер 36(8), С. 109594 - 109594

Опубликована: Авг. 1, 2021

The mesencephalic locomotor region (MLR) serves as an interface between higher-order motor systems and lower neurons. excitatory module of the MLR is composed pedunculopontine nucleus (PPN) cuneiform (CnF), their activation has been proposed to elicit different modalities movement. However, how differences in connectivity physiological properties explain contributions activity not well known. Here we report that CnF glutamatergic neurons are more electrophysiologically homogeneous than PPN have mostly short-range connectivity, whereas heterogeneous maintain long-range connections, most notably with basal ganglia. Optogenetic produces short-lasting muscle activation, driving involuntary activity. In contrast, neuron long-lasting increases tone reduce disrupt gait. Our results highlight biophysical functional attributes among support differential contribution behavior.

Язык: Английский

Процитировано

74
Muscarinic acetylcholine receptors for psychotic disorders: bench-side to clinic DOI Creative Commons
Samantha E. Yohn, Peter J. Weiden, Christian C. Felder

и другие.

Trends in Pharmacological Sciences, Год журнала: 2022, Номер 43(12), С. 1098 - 1112

Опубликована: Окт. 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.

Язык: Английский

Процитировано

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

Nature Communications, Год журнала: 2022, Номер 13(1)

Опубликована: Янв. 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.

Язык: Английский

Процитировано

56
Stress relief as a natural resilience mechanism against depression-like behaviors DOI Creative Commons
Yiyan Dong, Yifei Li, Xinkuan Xiang

и другие.

Neuron, Год журнала: 2023, Номер 111(23), С. 3789 - 3801.e6

Опубликована: Сен. 29, 2023

Relief, the appetitive state after termination of aversive stimuli, is evolutionarily conserved. Understanding behavioral role this well-conserved phenomenon and its underlying neurobiological mechanisms are open important questions. Here, we discover that magnitude relief from physical stress strongly correlates with individual resilience to depression-like behaviors in chronic stressed mice. Notably, blocking causes vulnerability behaviors, whereas natural rewards supplied shortly promotes resilience. Stress mediated by reward-related mesolimbic dopamine neurons, which show minute-long, persistent activation termination. Circuitry-wise, or inhibition circuits downstream ventral tegmental area during transient period bi-directionally regulates depression These results reveal an evolutionary function identify neural substrate mediating effect. Importantly, our data suggest a strategy augmenting positive valence prevent depression.

Язык: Английский

Процитировано

27
Deep tissue optical focusing and optogenetic modulation with time-reversed ultrasonically encoded light DOI Creative Commons
Haowen Ruan, Joshua Brake, J. Elliott Robinson

и другие.

Science Advances, Год журнала: 2017, Номер 3(12)

Опубликована: Дек. 1, 2017

Using ultrasound-guided optical wavefront shaping, the authors show enhanced optogenetic control in thick acute brain slices.

Язык: Английский

Процитировано

86
The State of the NIH BRAIN Initiative DOI Open Access
Walter J. Koroshetz, Joshua A. Gordon,

Amy Adams

и другие.

Journal of Neuroscience, Год журнала: 2018, Номер 38(29), С. 6427 - 6438

Опубликована: Июнь 19, 2018

The BRAIN Initiative arose from a grand challenge to "accelerate the development and application of new technologies that will enable researchers produce dynamic pictures brain show how individual cells complex neural circuits interact at speed thought." is public-private effort focused on use powerful tools for acquiring fundamental insights about information processing occurs in central nervous system (CNS). As enters its fifth year, NIH has supported >500 principal investigators, who have answered Initiative's via hundreds publications describing novel tools, methods, discoveries address seven scientific priorities. We describe advances produced by laboratories, multi-investigator teams, entire consortia that, over coming decades, more comprehensive maps brain, deepen our understanding circuit activity can rich tapestry behaviors, lay foundation circuitry disrupted disorders. Much work remains bring this vision fruition, National Institutes Health continues look diverse community, mathematics, physics, chemistry, engineering, neuroethics, neuroscience, ensure greatest benefit arises unique research Initiative.

Язык: Английский

Процитировано

70