VIPergic neurons of the infralimbic and prelimbic cortices control palatable food intake through separate cognitive pathways

Newmyer, Brandon A.; Whindleton, Ciarra M.; Klein, Peter; Beenhakker, Mark P.; Jones, Marieke K.; Scott, Michael M.

doi:10.1172/jci.insight.126283

Cited by 9 publications

(15 citation statements)

References 57 publications

(81 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Together with recent data from our laboratory and others 6,25-26 (Azevedo 2019, Newmyer 2019, Land 2014), this suggests that higher order brain regions which project downstream can integrate information about the surrounding environment and provide powerful modulation of basal feeding circuits which ultimately control behavioral output.…”

Section: Figuresupporting

confidence: 66%

A limbic circuit selectively linking active escape to food suppression

Tan

Pomeranz

Ivan

et al. 2019

Preprint

View full text Add to dashboard Cite

1Anorexia Nervosa (AN) is an eating disorder characterized by severe voluntary food 2 restriction 1 . Stress is known to be a precipitating factor in AN 2-5 , but the underlying biology 3 linking stress to feeding is not well understood. Here we describe a novel population of 4 stress-responsive neurons in the lateral septum (LS) that express neurotensin (Nts LS ) and 5 negatively regulate food intake. We used in vivo fiber photometry and chemo/optogenetics 6 to show that Nts LS neurons are activated by stressful experiences, including active escape 7 in a predator-induced stress paradigm, and specifically decrease food intake in mice, 8 without altering anxiety or locomotor behaviors. These neurons co-express Glp1r, and 9 pharmacologic or genetic manipulations of Glp1r signaling in the LS recapitulate the 10 behavioral findings shown using chemo/optogenetics. Finally, we mapped the outputs of 11Nts LS neurons and show that activation of Nts LS neuronal terminals in the lateral 12 hypothalamus (LH) also decrease food intake. Taken together, these results show that 13 NTS LS neurons serve as a potential link between stress and anorexia and act by modulating 14 hypothalamic pathways regulating feeding . 15 16 17 18 19 20 21 22 Voluntary food restriction, often to the point of starvation, is the canonical symptom 1 of Anorexia Nervosa (AN), which has the highest mortality rate of any psychiatric illness 1 . 2 Clinically, AN is often comorbid with depression, anxiety and stress disorders. Indeed, 3 stress is considered to be a common precipitating factor in the pathogenesis of the disease 2-4 5 . In a recent report, we found that a projection from Drd2-expressing neurons in the 5 hippocampus to the septal region reduces food intake 6 . Consistent with this, a prior study 6 showed that inhibitory neurons in the lateral septum (LS) have been implicated in the 7 modulation of appetite 7 . Because the LS is part of the anterior limbic system which 8 regulates emotional behaviors, particularly stress, anxiety and aggression 8-9 , we considered 9 the possibility that this region might link stress to reduced food intake. 10 We first exposed mice to acute restraint stress and examined the pattern of c-fos 11 within the LS. Consistent with previous experiments 10 , restraint stress was associated with 12 an increase in the number of c-fos+ cells in LS compared to controls ( Fig. 1a, Student's t-13 test, *p<0.05). Restraint stress also led to a decrease in food intake for the ensuing 2 hours 14 ( Fig. 1b, Two-way ANOVA with Bonferroni post-hoc, *p<0.05, ***P<0.001). Separate 15 studies previously identified a subpopulation of Neurotensin-expressing (Nts) neurons in 16 the LS 11 , and modulation of hypothalamic Nts neurons regulates feeding [12][13][14][15][16] . Therefore, 17we hypothesized that these neurons might respond to stress, and thus, modulate food intake. 18We first examined whether stress leads to activation of Nts LS neurons and whether 19 this accounted for the observed increase of c-fos activation ...

show abstract

Section: Figuresupporting

confidence: 66%

A limbic circuit selectively linking active escape to food suppression

Tan

Pomeranz

Ivan

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition, these findings may in time illuminate why in some cases stress can elicit a pathologic response such as in the case of eating disorders. These and other data further suggest that higher-order, limbic brain regions integrate diverse sensory information to modulate subcortical feeding circuits in health and possibly disease ( Azevedo et al, 2019 ; Newmyer et al, 2019 ; Land et al, 2014 ).…”

Section: Discussionmentioning

confidence: 55%

A limbic circuit selectively links active escape to food suppression

Tan

Pomeranz

Ivan

et al. 2020

eLife

View full text Add to dashboard Cite

Stress has pleiotropic physiologic effects, but the neural circuits linking stress to these responses are not well understood. Here, we describe a novel population of lateral septum neurons expressing neurotensin (LSNts) in mice that are selectively tuned to specific types of stress. LSNts neurons increase their activity during active escape, responding to stress when flight is a viable option, but not when associated with freezing or immobility. Chemogenetic activation of LSNts neurons decreases food intake and body weight, without altering locomotion and anxiety. LSNts neurons co-express several molecules including Glp1r (glucagon-like peptide one receptor) and manipulations of Glp1r signaling in the LS recapitulates the behavioral effects of LSNts activation. Activation of LSNts terminals in the lateral hypothalamus (LH) also decreases food intake. These results show that LSNts neurons are selectively tuned to active escape stress and can reduce food consumption via effects on hypothalamic pathways.

show abstract

“…In the prefrontal cortex (PFC), activation of NAc shell projecting neurons reduced food intake in a binge-eating model in rats predisposed to high impulsivity, a trait observed in a previous study 126 . Optogenetic activation of inhibitory VIP-expressing interneurons of infralimbic and prelimbic mPFC in male mice decreased BLE of a high caloric diet 127 . These findings implicate reduced function of the PFC->NAc circuit in impulsivity and BLE.…”

Section: Optogenetic and Chemogenetic Analysis Of Blementioning

confidence: 91%

Genetics and neurobiology of eating disorders

et al. 2022

View full text Add to dashboard Cite

Eating disorders (anorexia nervosa, bulimia nervosa, and binge-eating disorder) are a heterogeneous class of complex illnesses marked by weight and appetite dysregulation coupled with distinctive behavioral and psychological features. Our understanding of their genetics and neurobiology is evolving thanks to global cooperation on genome-wide association studies (GWAS), neuroimaging, and animal models. Until now, however, these approaches have advanced the field in parallel, with inadequate crosstalk. This review covers overlapping advances in these

show abstract

VIPergic neurons of the infralimbic and prelimbic cortices control palatable food intake through separate cognitive pathways

Cited by 9 publications

References 57 publications

A limbic circuit selectively linking active escape to food suppression

A limbic circuit selectively linking active escape to food suppression

A limbic circuit selectively links active escape to food suppression

Genetics and neurobiology of eating disorders

Contact Info

Product

Resources

About