Natural locus coeruleus dynamics during feeding

Sciolino, Natale R.; Hsiang, Madeline; Mazzone, Christopher M.; Wilson, Leslie R.; Plummer, Nicholas W.; Amin, Jaisal; Smith, Kathleen G.; McGee, Christopher; Fry, Sydney A.; Yang, Cindy X.; Powell, Jeanne M.; Bruchas, Michael R.; Kravitz, Alexxai V.; Cushman, Jesse D.; Krashes, Michael J.; Cui, Guohong; Jensen, Patricia

doi:10.1126/sciadv.abn9134

Cited by 19 publications

(33 citation statements)

References 81 publications

(148 reference statements)

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“…For example, noradrenergic LC neurons are considered to be an important circuit node for stress-related behaviors, such as stress-induced anorexia and anxiety-like behaviors. Indeed, activation of this circuitry elicits anorexia or anxiety-like behaviors [ 49 , 75 , 77 ]. However, inhibition of these neurons has no effect on basal feeding or anxiety-like behaviors [ 49 , 77 ].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, activation of this circuitry elicits anorexia or anxiety-like behaviors [ 49 , 75 , 77 ]. However, inhibition of these neurons has no effect on basal feeding or anxiety-like behaviors [ 49 , 77 ]. In addition, decades of studies have indicated that many stress hormones and neuropeptides modulate the HPA axis, dopamine system, and frontal cortical areas to elicit stress-related behaviors [ 2 , 78 ].…”

Section: Discussionmentioning

confidence: 99%

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Lateral Septum Somatostatin Neurons are Activated by Diverse Stressors

Kim

Park

et al. 2022

Exp Neurobiol

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The lateral septum (LS) is a forebrain structure that has been implicated in a wide range of behavioral and physiological responses to stress. However, the specific populations of neurons in the LS that mediate stress responses remain incompletely understood. Here, we show that neurons in the dorsal lateral septum (LSd) that express the somatostatin gene (hereafter, LSd Sst neurons) are activated by diverse stressors. Retrograde tracing from LSd Sst neurons revealed that these neurons are directly innervated by neurons in the locus coeruleus (LC), the primary source of norepinephrine well-known to mediate diverse stress-related functions in the brain. Consistently, we found that norepinephrine increased excitatory synaptic transmission onto LSd Sst neurons, suggesting the functional connectivity between LSd Sst neurons and LC noradrenergic neurons. However, optogenetic stimulation of LSd Sst neurons did not affect stress-related behaviors or autonomic functions, likely owing to the functional heterogeneity within this population. Together, our findings show that LSd Sst neurons are activated by diverse stressors and suggest that norepinephrine released from the LC may modulate the activity of LSd Sst neurons under stressful circumstances.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Lateral Septum Somatostatin Neurons are Activated by Diverse Stressors

Kim

Park

et al. 2022

Exp Neurobiol

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“…Increased LC engagement could set the stage for enhanced peri-LCNPY recruitment upon fasting. Thus, our NSF data might reflect an adaptive mechanism aimed to counteract increased LCNE tonic activity-induced avoidance/ aversion 12,53 , in favor of exploration of / foraging in new -and potentially unsafe environments-under conditions of limited food availability. In accordance with this notion, whereas peri-LCNPY activity levels influenced food-drive and consumption in the anxiogenic NSF task, it left consummatory behavior in the familiar (safe) context of the home-cage unaltered.…”

Section: Discussionmentioning

confidence: 94%

“…Notably, we report the lack of effect of in vivo peri-LC NPY inhibition in the EPM, implying divergent requirements for peri-LC NPY function in each task conditions. Of note, in the NSF, but not the EPM, mice were subjected to prior food deprivation, which is shown to increase LC neuronal activity during food approach 53 . Increased LC engagement could set the stage for enhanced peri-LC NPY recruitment upon fasting.…”

Section: Discussionmentioning

confidence: 99%

Neuropeptide Y neurons of the locus coeruleus inhibit noradrenergic system activity to reduce anxiety

Riga,

Rademakers,

Wolterink-Donselaar

et al. 2023

Preprint

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Adaptive responses to challenging environments depend on optimal function of the locus coeruleus (LC), the main source of noradrenaline in the brain and primary mediator of the initial stress response. Built-in systems that exert regulatory control over the LC are largely unidentified. A good candidate system is neuropeptide Y (NPY), which is traditionally linked to anxiety-relief. Currently, the endogenous source of NPY to the LC, and how NPY-expressing neurons modulate the noradrenergic system to regulate anxiety remain unclear. We here identify, in mice, a novel NPY-expressing neuronal population (peri-LCNPY) neighboring LC noradrenergic neurons that locally innervates the pericoerulean space. Moreover, we demonstrate that stress engages peri-LCNPY neurons, increasing their excitability. Mimicking peri-LCNPY neuronal activation using ex vivo chemogenetics suppresses LC noradrenergic neuron activity, via an NPY Y1 receptor-mediated mechanism. Furthermore, in vivo chemogenetic stimulation of peri-LCNPY neurons results in Y1R-dependent anxiety-relief. Conversely, inhibiting peri-LCNPY neurons increases anxiety-like behaviors. Together, we establish a causal role for peri-LCNPY-mediated neuromodulation of the LC in the regulation of anxiety, providing novel insights in the endogenous mechanisms underlying adaptive responses to adversity.

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“…Behavioral-event-triggered averages were used to analyze the photometry data across groups using the custom coded fiber photometry analysis script (FiPhA), coded in R ((70); Fig. S4).…”

Section: Methodsmentioning

confidence: 99%

Partial or complete loss of norepinephrine differentially alters contextual fear and catecholamine release dynamics in hippocampal CA1

Wilson

Plummer

Evsyukova

et al. 2023

Preprint

Self Cite

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Contextual fear learning is heavily dependent on the hippocampus. Despite evidence that catecholamines contribute to contextual encoding and memory retrieval, the precise temporal dynamics of their release in the hippocampus during behavior is unknown. In addition, new animal models are required to probe the effects of altered catecholamine synthesis on release dynamics and contextual learning. Utilizing GRABNE and GRABDA sensors, in vivo fiber photometry, and two new mouse models of altered locus coeruleus norepinephrine (LC-NE) synthesis, we investigate norepinephrine (NE) and dopamine (DA) release dynamics in dorsal hippocampal CA1 during contextual fear conditioning. We report that aversive foot-shock increases both NE and DA release in dorsal CA1, while freezing behavior associated with recall of fear memory is accompanied by decreased release. Partial loss of LC-NE synthesis reveals that NE release dynamics are modulated by sex. Moreover, we find that recall of recent fear memory is sensitive to both partial and complete loss of LC-NE synthesis throughout prenatal and postnatal development, similar to prior observations of mice with global loss of NE synthesis beginning postnatally. In contrast, remote recall is compromised only by complete loss of LC-NE synthesis beginning prenatally. Overall, these findings provide novel insights into the role of NE in contextual fear and the precise temporal dynamics of both NE and DA during freezing behavior, and highlight a complex relationship between genotype, sex, and NE signaling.

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Natural locus coeruleus dynamics during feeding

Cited by 19 publications

References 81 publications

Lateral Septum Somatostatin Neurons are Activated by Diverse Stressors

Lateral Septum Somatostatin Neurons are Activated by Diverse Stressors

Neuropeptide Y neurons of the locus coeruleus inhibit noradrenergic system activity to reduce anxiety

Partial or complete loss of norepinephrine differentially alters contextual fear and catecholamine release dynamics in hippocampal CA1

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