Age-related Increase in Locus Coeruleus Activity and Connectivity with Prefrontal Cortex during Ambiguity Processing DOI Creative Commons

Arjun Dave,

Shuer Ye, Leona Rahel Bätz

et al.

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

Published: Dec. 21, 2024

Abstract Interpreting ambiguous environmental cues, like facial expressions, becomes increasingly challenging with age, especially as cognitive resources decline. Managing these challenges requires adaptive neural mechanisms that are essential for maintaining mental well-being. The locus coeruleus (LC), the brain’s main norepinephrine source, regulates attention, arousal, and stress response. With extensive cortical connections, LC supports adapting to demands resolving conflicting cues from environment, particularly in later life. Previous research suggests interacts prefrontal cortex during high-conflict tasks. However, whether activity its connectivity PFC support emotional ambiguity processing contributes well-being healthy aging remains unclear. To address this gap, we used 7T-MRI examine function 75 younger (25.8±4.02years, 35females) 69 older adults (71.3±4.1 years, emotion-recognition task morphed varying ambiguity: anchor (unambiguous happy or fearful), intermediate- (30% happy–70% fearful 40%-happy–60% either direction), absolute-ambiguity (50% happy-fearful). Behaviorally, participants had longer response times lower confidence condition, while perceived faces more frequently than adults. Neuroimaging results revealed exhibited greater enhanced dorsolateral (dlPFC) compared This heightened was linked better resilience These findings suggest managing cognitively demanding tasks, LC-dlPFC helps maintain well- being, underscoring importance of pathway aging. Significance Statement Understanding how brain adapts age is key promoting study examined a region critical regulating attention undergoes changes task. Using ultra-high-field imaging, explored recognize expressions levels. Our indicated young, showed LC-dorsolateral when absolute-ambiguous improved higher LC- dlPFC resilience, offering insights into underlying

Language: Английский

Chronic stress-induced neuroplasticity in the prefrontal cortex: Structural, functional, and molecular mechanisms from development to aging DOI
Sami A. Algaidi

Brain Research, Journal Year: 2025, Volume and Issue: unknown, P. 149461 - 149461

Published: Jan. 1, 2025

Language: Английский

Citations

0
Early signs of neuron autonomous and non‐autonomous hyperexcitability in locus coeruleus noradrenergic neurons of a mouse model of tauopathy and Alzheimer's disease DOI Open Access

Zhong‐Min Wang,

Valentina P. Grinevich,

William R. Meeker

et al.

Acta Physiologica, Journal Year: 2025, Volume and Issue: 241(4)

Published: March 14, 2025

Abstract Aim The locus coeruleus (LC) is one of the earliest brain regions affected by phosphorylated tau (p‐tau) in Alzheimer's disease (AD). Using P301S mouse model, we investigated temporal progression pathology and its functional consequences. Methods Immunohistochemistry was used to assess p‐tau deposition LC noradrenergic neurons at 2–3 5–6 months. Electrophysiological recordings evaluated neuronal hyperexcitability, measuring membrane potential, rheobase, spontaneous action potential (AP) frequency wild‐type (WT) mice. Fast‐scan cyclic voltammetry (FSCV) measure norepinephrine (NE) release. GABA(A) receptor subunit expression analyzed via immunoblotting. Results P‐tau detected as early months, with a rostral‐to‐caudal gradient, nearly all exhibited immunoreactivity. showed characterized depolarized potentials, more negative increased AP frequency. Synaptic blockade elicited reduced increase frequency, suggesting diminished inhibitory tone. α2 significantly declined age mice, whereas α3 remained unchanged. FSCV elevated NE release mice 3 6 months compared WT. Conclusion findings highlight dysfunction tauopathies, excitability, tone, exaggerated This hyperactivity may contribute excitotoxicity downstream LC‐regulated regions. Targeting restoring signaling could be promising therapeutic strategies for mitigating AD progression.

Language: Английский

Citations

0
Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors DOI Creative Commons
Michael A. Kelberman, Ellen M. Rodberg, Ehsan Arabzadeh

et al.

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

Published: Oct. 16, 2024

Abstract The brainstem region, locus coeruleus (LC), has been remarkably conserved across vertebrates. Evolution woven the LC into wide-ranging neural circuits that influence functions as broad autonomic systems, stress response, nociception, sleep, and high-level cognition among others. Given this conservation, there is a strong possibility activity inherently similar species, furthermore age, sex, brain state similarly species. degree to which homogenous these factors, however, never assessed due small sample size of individual studies. Here, we pool data from 20 laboratories (1,855 neurons) show diversity both intrinsic extrinsic factors such sex state. We use negative binomial regression model compare male monkeys, rats mice sexes were recorded states slices ex vivo or under different anesthetics during wakefulness in . differed complex interactions became more active aging, independent sex. Finally, contrast foundational principle all species express two distinct firing modes (“tonic” “phasic”), discovered great within spontaneous patterns. Different associated with higher incidence some modes. conclude evolutionarily-ancient not conserved. Inherent differences age species-sex-brain have implications for understanding role species-specific naturalistic behavior, well psychiatric disorders, cardiovascular disease, immunology, metabolic disorders.

Language: Английский

Citations

3
Age-related Increase in Locus Coeruleus Activity and Connectivity with Prefrontal Cortex during Ambiguity Processing DOI Creative Commons

Arjun Dave,

Shuer Ye, Leona Rahel Bätz

et al.

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

Published: Dec. 21, 2024

Abstract Interpreting ambiguous environmental cues, like facial expressions, becomes increasingly challenging with age, especially as cognitive resources decline. Managing these challenges requires adaptive neural mechanisms that are essential for maintaining mental well-being. The locus coeruleus (LC), the brain’s main norepinephrine source, regulates attention, arousal, and stress response. With extensive cortical connections, LC supports adapting to demands resolving conflicting cues from environment, particularly in later life. Previous research suggests interacts prefrontal cortex during high-conflict tasks. However, whether activity its connectivity PFC support emotional ambiguity processing contributes well-being healthy aging remains unclear. To address this gap, we used 7T-MRI examine function 75 younger (25.8±4.02years, 35females) 69 older adults (71.3±4.1 years, emotion-recognition task morphed varying ambiguity: anchor (unambiguous happy or fearful), intermediate- (30% happy–70% fearful 40%-happy–60% either direction), absolute-ambiguity (50% happy-fearful). Behaviorally, participants had longer response times lower confidence condition, while perceived faces more frequently than adults. Neuroimaging results revealed exhibited greater enhanced dorsolateral (dlPFC) compared This heightened was linked better resilience These findings suggest managing cognitively demanding tasks, LC-dlPFC helps maintain well- being, underscoring importance of pathway aging. Significance Statement Understanding how brain adapts age is key promoting study examined a region critical regulating attention undergoes changes task. Using ultra-high-field imaging, explored recognize expressions levels. Our indicated young, showed LC-dorsolateral when absolute-ambiguous improved higher LC- dlPFC resilience, offering insights into underlying

Language: Английский

Citations

0