Tonic activation of norepinephrine

Catecholamine signaling is thought to modulate cognition in an inverted-U relationship, but the mechanisms are unclear. We measured norepinephrine and dopamine release, postsynaptic calcium responses, and interactions between tonic and phasic firing modes under various stimuli and conditions. High tonic activity in vivo depleted catecholamine stores, desensitized postsynaptic responses, and decreased phasic transmission. Together, these findings provide a more complete understanding of the inverted-U relationship, offering insights into psychiatric disorders and neurodegenerative diseases with impaired catecholamine signaling...

The locus coeruleus-norepinephrine (LC-NE) system, which regulates arousal levels, is important for cognitive control, including emotional conflict resolution. Additionally, the LC-NE system is implicated in P300 generation. If the P300 is mediated by the LC-NE system, and considering the established correlations between LC activity and pupil dilation, P300 amplitude should correlate with task-evoked (phasic) pupil dilation on a trial-by-trial basis. However, prior studies, predominantly utilizing oddball-type paradigms, have not demonstrated correlations between concurrently recorded task-evoked pupil dilation and P300 responses...

BACKGROUND: Autistic individuals excel at visual search, however, the neural mechanism(s) underlying this advantage remain unclear. The locus coeruleus-norepinephrine (LC-NE) system, which plays a critical role in sensory perception and selective attention, has been shown to function in a persistently elevated state in individuals on the spectrum. However, the relationship between elevated tonic LC-NE activity and accelerated search in autism has not been explored. OBJECTIVE: To examine the relationship between visual search abilities and resting pupil diameter (an indirect measure of tonic LC-NE activation) in autistic and neurotypical children...

BACKGROUND: Accurate senses depend on high fidelity encoding by sensory receptors and error-free central processing in the brain. Progress has been made towards restoring damaged sensory receptors. However, methods for providing on demand treatment of impaired central sensory processing arising from factors including aging, neurological dysfunction, inattention, and fatigue are scarce. Recent studies have demonstrated that tonic vagus nerve stimulation in rodents can activate the locus coeruleus-norepinephrine system in the brain to improve sensory processing rapidly and continuously...

Catecholamine signaling is thought to modulate cognition in an inverted-U relationship, but the mechanisms are unclear. We measured norepinephrine and dopamine release, postsynaptic calcium responses, and interactions between tonic and phasic firing modes under various stimuli and conditions. High tonic activity in vivo depleted catecholamine stores, desensitized postsynaptic responses, and decreased phasic transmission. Together this provides a clearer understanding of the inverted-U relationship, offering insights into psychiatric disorders and neurodegenerative diseases with impaired catecholamine signaling...

The norepinephrine locus coeruleus system (LC NE) represents a promising treatment target in patients with insomnia disorder (ID) due to its well understood links to arousal and sleep regulation. However, consistent markers of LC NE activity are lacking. This study measured three potential indirect markers of LC NE activity - REM sleep, P3 amplitude during an auditory oddball paradigm (as a marker of phasic LC activation), and baseline pupil diameter (as a marker of tonic LC activation). The parameters were then combined in a statistical model and tested to compare LC NE activity between 20 subjects with insomnia disorder (13 female; age 44...

A growing body of research suggests that locus coeruleus-norepinephrine (LC-NE) system may function differently in individuals with autism spectrum disorder (ASD). Understanding the dynamics of both tonic (resting pupil diameter) and phasic (pupil dilation response [PDR] and event-related potential [ERP]) indices may provide meaningful insights about the nature of LC-NE function in ASD. Twenty-four children with ASD and 27 age- and nonverbal-IQ matched typically developing (TD) children completed two experiments: (1) a resting eye-tracking task to measure tonic pupil diameter, and (2) a three-stimulus oddball paradigm to measure phasic responsivity using PDR and ERP...

Recently, we have shown that pupil dilation during a recognition memory task can serve as an index of memory retrieval difficulties in autism. At the time of publication, we were unaware of specific data-analysis methods that can be used to shed further light on the origins of such memory related pupil dilation. Specifically, by distinguishing "tonic" from "phasic" changes in pupil dilation and considering their temporal progression, it is possible to draw inferences about the functional integrity of a locus coeruleus-norepinephrine system (LC-NE) that is known to play a key role in regulating memory encoding and retrieval processes...

Autism spectrum disorder (ASD) is a developmental disorder that is characterized by difficulties with social interaction and interpersonal communication. It has been argued that abnormal attentional function to exogenous stimuli precedes and contributes to the core ASD symptoms. Notably, the locus ceruleus (LC) and its noradrenergic projections throughout the brain modulate attentional function, but the extent to which this locus ceruleus-norepinephrine (LC-NE) system influences attention in individuals with ASD, who frequently exhibit dysregulated alerting and attention orienting, is unknown...

Reward exploitation and aversion are mediated in part by the locus coeruleus (LC), a brainstem structure significantly involved in learning and memory via the release of norepinephrine. Different LC firing patterns are associated with different functions. Previously, we have shown that high tonic and phasic LC activation signal negative and positive valence, respectively, via basolateral amygdala (BLA) circuitry. Tonic LC activation is associated preferentially with BLA-central amygdala (CeA) activation, while phasic LC stimulation preferentially recruits the BLA-nucleus accumbens (NAc) pathway...

G-protein coupled receptors such as α1 -adrenergic receptors (AR) are linked via the G-protein Gq /G11 to both Ca2+ entry and release of Ca2+ from stores, but can also activate the small GTP binding protein RhoA and Rho kinase to produce contractions involving Ca2+ sensitization. In rat portal vein, tonic but not phasic components of contractions to the α1 -AR agonist phenylephrine involve predominantly the α1B -AR subtype, and are at least partly mediated by mechanisms involving Rho kinase sensitive to fasudil (Alsufyani & Docherty, 2021)...

The default mode network (DMN) of the brain is functionally associated with a wide range of behaviors. In this study, we used functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and spectral fiber photometry to investigate the selective neuromodulatory effect of norepinephrine (NE)-releasing noradrenergic neurons in the locus coeruleus (LC) on the mouse DMN. Chemogenetic-induced tonic LC activity decreased cerebral blood volume (CBV) and glucose uptake and increased synchronous low-frequency fMRI activity within the frontal cortices of the DMN...

OBJECTIVE: Talbinah is a traditional barley porridge used as food and brain tonic by Arabs to alleviate depression and reduce stress. It is a food product with the high potentiality to be used as a functional food. The present study was designed to explore the antidepressant-like effects of Talbinah (Barley porridge). MATERIALS AND METHODS: Thirty-two adult rats were assigned into four groups: negative control group (normal environment), stress-model group, Prozac-treated stress group, and Talbinah treated stress group...

BACKGROUND: Recent clinical studies demonstrate that SGLT2 (sodium-glucose cotransporter 2) inhibitors ameliorate heart failure (HF). The present study was conducted to assess the expression and function of renal SGLT2 and the influence of enhanced renal sympathetic tone in HF. METHODS: Four weeks after coronary artery ligation surgery to induce HF, surgical bilateral renal denervation (RDN) was performed in rats. Four groups of rats (Sham-operated control [Sham], Sham+RDN, HF and HF+RDN; n=6/group) were used...

Background: Differences in non-social attentional functions have been identified as among the earliest features that distinguish infants later diagnosed with autism spectrum disorder (ASD), and may contribute to the emergence of core ASD symptoms. Specifically, slowed attentional disengagement and difficulty reorienting attention have been found across the lifespan in those at risk for, or diagnosed with, ASD. Additionally, the locus coeruleus-norepinephrine (LC-NE) system, which plays a critical role in arousal regulation and selective attention, has been shown to function atypically in ASD...

Previous research has established an impact of acute exercise on cognitive performance, which has inspired investigations into neurobiological mechanisms that may underlie the observed benefits. Pupillary responses have been posited to reflect activation of such underlying neurobiological mechanisms. The current study recruited healthy young adults to investigate the effects of a single bout of moderate-to-vigorous intensity aerobic exercise on subsequent performance and pupillary responses during an inhibitory control task...

Objective: These experiments sought to characterize the effects of obesity propensity and obesogenic diet on locus coeruleus (LC) norepinephrine (NE) activity and determine the effects of obesity on LC neural responses to morphine withdrawal. Methods: In vivo single-unit LC electrophysiological activity was measured in obese prone (OP) and obese resistant (OR) male SD rats following high-fat (HFD: 45% fat) or low-fat (LFD; 10% fat) feeding. A separate cohort of LFD and HFD rats underwent in vivo LC recording on day 3 of spontaneous morphine withdrawal following an escalation dose paradigm (5-15 mg/kg; SQ twice daily)...

Dysregulation in contextual processing is believed to affect several forms of psychopathology, such as post-traumatic stress disorder (PTSD). The dentate gyrus (DG), a subregion of the hippocampus, is thought to be an important brain region for disambiguating new experiences from prior experiences. Noradrenergic (NE) neurons in the locus coeruleus (LC) are more tonically active during stressful events and send dense projections to the DG, yet an understanding of their function in DG-dependent contextual discrimination has not been established...

Recent findings from this laboratory demonstrate that ethanol reduces the intrinsic excitability of orbitofrontal cortex (OFC) neurons via activation of strychnine-sensitive glycine receptors. Although the mechanism linking ethanol to the release of glycine is currently unknown, astrocytes are a source of neurotransmitters including glycine and activation of dopamine D1-like receptors has been reported to enhance extracellular levels of glycine via a functional reversal of the astrocytic glycine transporter GlyT1...

BACKGROUND: Atypical arousal regulation may explain slower mean reaction time (MRT) in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder compared with typical development. The locus coeruleus-norepinephrine system (LC-NE) underlies arousal regulation and adapts its activity to the utility of a task. LC-NE tonic and phasic activity are indexed by baseline pupil size (BPS) and stimulus-evoked pupillary response (SEPR). METHODS: The study assessed pupillometry in ASD (n = 31, 3 female/28 male), attention-deficit/hyperactivity disorder (n = 28, 3 female/25 male), and typically developing control subjects (n = 31, 16 female/15 male) during a visuospatial reaction-time task that manipulates arousal by conditions with low and high task utility...