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A limbic circuit selectively links active escape to food suppression.

ABSTRACT: 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.

SUBMITTER: Azevedo EP

PROVIDER: S-EPMC7476759 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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A limbic circuit selectively links active escape to food suppression.

Azevedo Estefania P EP Tan Bowen B Pomeranz Lisa E LE Ivan Violet V Fetcho Robert R Schneeberger Marc M Doerig Katherine R KR Liston Conor C Friedman Jeffrey M JM Stern Sarah A SA

eLife 20200907

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 (LS<sup>Nts</sup>) in mice that are selectively tuned to specific types of stress. LS<sup>Nts</sup> 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 ...[more]

PMID: 32894221

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Project description:Limbic encephalitis (LE) is an autoimmune syndrome often associated with temporal lobe epilepsy. Recent research suggests that particular structural changes in LE depend on the type of the associated antibody and occur in both mesiotemporal gray matter and white matter regions. However, it remains questionable to what degree conventional diffusion tensor imaging (DTI)-methods reflect alterations in white matter microstructure, since these methods do not account for crossing fibers. To address this methodological shortcoming, we applied fixel-based analysis as a novel technique modeling distinct fiber populations. For our study, 19 patients with LE associated with autoantibodies against glutamic acid decarboxylase 65 (GAD-LE, mean age = 35.9 years, 11 females), 4 patients with LE associated with autoantibodies against leucine-rich glioma-inactivated 1 (LGI1-LE, mean age = 63.3 years, 2 females), 5 patients with LE associated with contactin-associated protein-like 2 (CASPR2, mean age = 57.4, 0 females), 20 age- and gender-matched control patients with hippocampal sclerosis (19 GAD-LE control patients: mean age = 35.1 years, 11 females; 4 LGI1-LE control patients: mean age = 52.6 years, 2 females; 5 CASPR2-LE control patients: mean age = 42.7 years, 0 females; 10 patients are included in more than one group) and 33 age- and gender-matched healthy control subjects (19 GAD-LE healthy controls: mean age = 34.6 years, 11 females; 8 LGI1-LE healthy controls: mean age = 57.0 years, 4 females, 10 CASPR2-LE healthy controls: mean age = 57.2 years, 0 females; 4 subjects are included in more than one group) underwent structural imaging and DTI at 3 T and neuropsychological testing. Patient images were oriented according to lateralization in EEG resulting in an affected and unaffected hemisphere. Fixel-based metrics fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC = FD · FC) were calculated to retrieve information about white matter integrity both on the micro- and the macroscale. As compared to healthy controls, patients with GAD-LE showed significantly (family-wise error-corrected, p < 0.05) lower FDC in the superior longitudinal fascicle bilaterally and in the isthmus of the corpus callosum. In CASPR2-LE, lower FDC in the superior longitudinal fascicle was only present in the affected hemisphere. In LGI1-LE, we did not find any white matter alteration of the superior longitudinal fascicle. In an explorative tract-based correlation analysis within the GAD-LE group, only a correlation between the left/right ratio of FC values of the superior longitudinal fascicle and verbal memory performance (R = 0.64, Holm-Bonferroni corrected p < 0.048) remained significant after correcting for multiple comparisons. Our results underscore the concept of LE as a disease comprising a broad and heterogeneous group of entities and contribute novel aspects to the pathomechanistic understanding of this disease that may strengthen the role of MRI in the diagnosis of LE.

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A limbic circuit selectively links active escape to food suppression.

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A limbic circuit selectively links active escape to food suppression.

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