Monosynaptic ventral tegmental area glutamate projections to the locus coeruleus enhance aversive processing DOI Creative Commons
Kyle E. Parker, Chao‐Cheng Kuo, Alex R. Buckley

et al.

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

Published: Oct. 5, 2024

Distinct excitatory synaptic inputs to the locus coeruleus (LC) modulate behavioral flexibility. Here we identify a novel monosynaptic glutamatergic input LC from ventral tegmental area (VTA). We show robust VTA axonal projections provide direct transmission LC. Despite weak summation, optogenetic activation of these axons enhances tonic firing and facilitates real-time conditioned aversive behaviors. hypothesized this projection may integration with other inputs. then used coincident VTA-LC photostimulation local electrical stimulation observed enhanced burst induction. To determine whether also occurs in vivo, took an analogous approach measuring reward-seeking behavior during unpredictable probabilistic punishment. Here, concurrent noxious stimulus did not delay behavior, but increased probability task failure. Together, identified that drives summation salient stimuli promote avoidance.

Language: Английский

The ‘in’s and out’s’ of descending pain modulation from the rostral ventromedial medulla DOI
Caitlynn C. De Preter,

Mary M. Heinricher

Trends in Neurosciences, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Language: Английский

Citations

7
Neural circuit-selective, multiplexed pharmacological targeting of prefrontal cortex-projecting locus coeruleus neurons drives antinociception DOI Creative Commons
Chao‐Cheng Kuo, Jordan G. McCall

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

Published: June 8, 2024

Selective manipulation of neural circuits using optogenetics and chemogenetics holds great translational potential but requires genetic access to neurons. Here, we demonstrate a general framework for identifying tool-independent, pharmacological strategies circuit-selective modulation. We developed an economically accessible calcium imaging-based approach large-scale scans endogenous receptor-mediated activity. As testbed this approach, used the mouse locus coeruleus due combination its widespread, modular efferent circuitry wide variety endogenously expressed GPCRs. Using machine learning-based action deconvolution retrograde tracing, identified agonist cocktail that selectively inhibits medial prefrontal cortex-projecting

Language: Английский

Citations

4
Activation of the periaqueductal gray controls respiratory output through a distributed brain network DOI Creative Commons

Mitchell Prostebby,

Jashan Saini, Vivian Biancardi

et al.

Frontiers in Physiology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 22, 2025

Introduction The periaqueductal gray (PAG) has been previously established to play a key role in producing the vital changes respiration occurring response threat. However, it is not fully understood how PAG activation alters ongoing respiratory output, nor which pathways mediate these effects, as several regions have identified influence activity. Methods We used optogenetic tools conjunction with EMG recordings of inspiratory and expiratory musculature determine on short (250 ms) longer (10–15 s) timescales muscle Through cFOS mapping, we also downstream brain were likely modulated by including preBötzinger Complex (preBötC) lateral parafacial area (pFL). then stimulated terminals those whether their activity can account for observed effects stimulation. Results Directly stimulating resulted prominent all recorded activities reset breathing rhythm either phase-independent or phase-dependent manner. In contrast, preBötC pFL long shorter timescale stimuli could completely replicate direct stimulation did produce any reset. Conclusions Our results show that are mediated solely inputs more involve integration across larger network brainstem areas.

Language: Английский

Citations

0
Biochemical strategies for opioid-sparing pain management in the operating room DOI
Fatemeh Hosseinzadeh, Alireza Nourazarian

Biochemistry and Biophysics Reports, Journal Year: 2025, Volume and Issue: 41, P. 101927 - 101927

Published: Jan. 25, 2025

Language: Английский

Citations

0
Top-down control of the descending pain modulatory system drives placebo analgesia DOI Creative Commons
Giulia Livrizzi, Jingzhu Liao, Desiree A. Johnson

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 16, 2025

In placebo analgesia, prior experience and expectations lead to pain suppression by the administration of an inert substance, but causal evidence for its neural basis is lacking. To identify underlying circuits, we reverse-translated a conditioned protocol from humans mice. Surprisingly, effect suppresses both nociception unconditioned emotional-motivational pain-related behavior. Descending modulatory neurons in periaqueductal gray (PAG) are critical morphine antinociception. The depends on input PAG medial prefrontal anterior cingulate cortices, not insular cortex. Conditioning enhances noxious stimulus-evoked endogenous opioid release produce analgesia. Our results suggest that cortical control descending system (DPMS) gated rapid signaling during trials. This study bridges clinical preclinical research, establishing central role DPMS

Language: Английский

Citations

0
Subtle behavioral alterations in the spontaneous behaviors of MPTP mouse model of Parkinson’s disease DOI Creative Commons
Hao Zhong,

Kangrong Lu,

Liping Wang

et al.

Translational Psychiatry, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 3, 2025

Midbrain dopamine (DA) neurons are essential for regulating movement, emotion, and reward, with their dysfunction closely linked to Parkinson's disease (PD). While DA in the substantia nigra pars compacta (SNc) ventral tegmental area (VTA) have known overlapping roles behaviors such as depression distinct contributions subtle spontaneous remain insufficiently understood. In this study, we utilized a 3D behavioral analysis platform powered by machine learning explore motor nuanced changes subacute MPTP mouse model of PD. This investigative approach was combined cell-type-specific genetic ablation both SNc VTA. Our findings highlight significant deficits rearing, walking, hunching correlated loss neurons, but not VTA alongside increased overall reduced movement precision, pronounced right-sided lateralization. These features, particularly rearing lateralization, emerge critical biomarkers neuron loss, thereby enhancing translational relevance PD models.

Language: Английский

Citations

0
The Locus Coeruleus in Chronic Pain DOI Open Access

Jorge Castejón España,

Anusha Mohan, Sven Vanneste

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(16), P. 8636 - 8636

Published: Aug. 8, 2024

Pain perception is the consequence of a complex interplay between activation and inhibition. Noradrenergic pain modulation inhibits nociceptive transmission perception. The main source norepinephrine (NE) in central nervous system Locus Coeruleus (LC), small but cluster cells pons. aim this study to review literature on LC-NE inhibitory system, its influence chronic pathways frequent comorbidities. research showed that environmental processing modulated by system. If perpetuated time, inputs can generate neuroplastic changes reduce effects facilitate development comorbidities, such as anxiety, depression or sleeping disturbances. exact mechanisms involved LC functional shift remain unknown, there some evidence they occur through plastic medial lateral their brain projections. Additionally, are other influencing factors, like developmental issues, neuroinflammatory glial changes, NE receptor affinity neuronal firing rates.

Language: Английский

Citations

2
Neuroanatomy of the nociceptive system: From nociceptors to brain networks DOI
Julian C. Motzkin, Allan I. Basbaum, Andrew Crowther

et al.

International review of neurobiology, Journal Year: 2024, Volume and Issue: unknown, P. 1 - 39

Published: Jan. 1, 2024

Language: Английский

Citations

2
Restraint stress-induced antinociceptive effects in acute pain: Involvement of orexinergic system in the nucleus accumbens DOI

Danial Farmani,

Seyed Mohammadmisagh Moteshakereh, Mohammad Nikoohemmat

et al.

Behavioural Brain Research, Journal Year: 2024, Volume and Issue: 472, P. 115133 - 115133

Published: July 1, 2024

Language: Английский

Citations

1
Elevating levels of the endocannabinoid 2-arachidonoylglycerol blunts opioid reward but not analgesia DOI Creative Commons
Arlene Martínez-Rivera, Robert N. Fetcho,

Lizzie Birmingham

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(48)

Published: Nov. 29, 2024

Converging findings have established that the endocannabinoid (eCB) system serves as a possible target for development of new treatments complement to opioid-based treatments. Here, we show in male and female mice enhancing levels eCB, 2-arachidonoylglycerol (2-AG), through pharmacological inhibition its catabolic enzyme, monoacylglycerol lipase (MAGL), either systemically or ventral tegmental area (VTA) with JZL184, leads substantial attenuation rewarding effects opioids using conditioned place preference self-administration paradigms, without altering their analgesic properties. These are driven by cannabinoid receptor 1 (CB1R) within VTA, VTA CB1R conditional knockout counteracts JZL184’s effects. Using fiber photometry fluorescent sensors calcium dopamine (DA), find 2-AG diminishes opioid reward–related nucleus accumbens (NAc) activity DA neurotransmission. Together, these reveal properties provides potential adjunctive therapeutic strategy opioid-related

Language: Английский

Citations

1