A Brainstem Locomotor Circuit Drives the Activity of Speed Cells in the Medial Entorhinal Cortex DOI Creative Commons
Miguel M. Carvalho, Nouk Tanke, Emilio Kropff

et al.

Cell Reports, Journal Year: 2020, Volume and Issue: 32(10), P. 108123 - 108123

Published: Sept. 1, 2020

Locomotion activates an array of sensory inputs that may help build the self-position map medial entorhinal cortex (MEC). In this map, speed-coding neurons are thought to dynamically update representations animal's position. A possible origin for speed signal is mesencephalic locomotor region (MLR), which critically involved in activation programs. Here, we describe, rats, a circuit connecting pedunculopontine tegmental nucleus (PPN) MLR MEC via horizontal limb diagonal band Broca (HDB). At each level pathway, locomotion linearly encoded neuronal firing rates. Optogenetic PPN cells drives and modulates activity speed-modulated HDB MEC. Our results provide evidence pathway by brainstem signals can reach cortical structures implicated navigation higher-order dynamic space.

Language: Английский

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

Ludwig Ruder,

Paolo Capelli

et al.

Neuron, Journal Year: 2018, Volume and Issue: 100(2), P. 361 - 374

Published: Oct. 1, 2018

Language: Английский

Citations

130
Dopamine and the Brainstem Locomotor Networks: From Lamprey to Human DOI Creative Commons
Dimitri Ryczko, Réjean Dubuc

Frontiers in Neuroscience, Journal Year: 2017, Volume and Issue: 11

Published: May 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.

Language: Английский

Citations

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

et al.

Acta Pharmacologica Sinica, Journal Year: 2019, Volume and Issue: 41(1), P. 1 - 9

Published: Sept. 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.

Language: Английский

Citations

88
Temporally restricted dopaminergic control of reward-conditioned movements DOI
Kwang Lee, Leslie D. Claar, Ayaka Hachisuka

et al.

Nature Neuroscience, Journal Year: 2020, Volume and Issue: 23(2), P. 209 - 216

Published: Jan. 13, 2020

Language: Английский

Citations

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

Adrienn Kovács,

Tsogbadrakh Bayasgalan

et al.

Cell Reports, Journal Year: 2021, Volume and Issue: 36(8), P. 109594 - 109594

Published: Aug. 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.

Language: Английский

Citations

73
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
Stress relief as a natural resilience mechanism against depression-like behaviors DOI Creative Commons
Yiyan Dong, Yifei Li, Xinkuan Xiang

et al.

Neuron, Journal Year: 2023, Volume and Issue: 111(23), P. 3789 - 3801.e6

Published: Sept. 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.

Language: Английский

Citations

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

et al.

Science Advances, Journal Year: 2017, Volume and Issue: 3(12)

Published: Dec. 1, 2017

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

Language: Английский

Citations

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

Amy Adams

et al.

Journal of Neuroscience, Journal Year: 2018, Volume and Issue: 38(29), P. 6427 - 6438

Published: June 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.

Language: Английский

Citations

70