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

8
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
Heterogeneous pericoerulear neurons tune arousal and exploratory behaviours DOI
Andrew T. Luskin, Li Li,

Xiaonan Fu

et al.

Nature, Journal Year: 2025, Volume and Issue: unknown

Published: May 7, 2025

Language: Английский

Citations

0
Mas Receptor as a Target for Neuropathic Pain Management: Insights into Angiotensin-(1-7) Signaling and Therapeutic Opportunities DOI

Surekha A. Devi,

Saajan Kumar Sharma,

Sandip Tejpal

et al.

Journal for Research in Applied Sciences and Biotechnology, Journal Year: 2025, Volume and Issue: 4(2), P. 167 - 176

Published: April 30, 2025

Mas is a G protein-coupled receptor (GPCR) that binds to Angiotensin (1-7) and it evaluated as an important element of non classical Renin System. While the RAS axis has been considered pro-inflammatory pro-nociceptive by leveraging II AT1 receptor, /Mas offers anti-inflammatory, vessels dilating, neuroprotective functions. It produced two mechanisms first, obtained from via mechanism angiotensin converting enzyme 2 (ACE2) also binding formed Ang-(1-7) its activates several signaling pathways such PI3K/Akt, ERK1/2 nitric oxide (NO). These together prevent neuronal death, decrease oxidative stress inhibit nuclear factor-kappa B (NF-κB), reduces expression various cytokines like TNF-α, IL-1β IL-6. With regard neuropathic pain, contributes regulation glial-neuronal crosstalk negative microglial astrocytic activity neuroimmune balance. Experimental studies have shown use or synthetic activators attenuates mechanical alodynia thermal hypoesthesia, proving Marques colleagues’ hypothesis possible therapeutic applications. Also, functional cross-talk with other pain-modulatory systems, including endogenous opioid endocannabinoid contributing enhancer this sort analgesia. Thus, novel (1-7)/Mas pathway can be promising candidate for new non-opioid analgesic treatment pain. Further research in agonists, peptide analogs, targeted drug delivery system shows there potential practical application these discoveries.

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