Prepronociceptin-Expressing Neurons in the Extended Amygdala Encode and Promote Rapid Arousal Responses to Motivationally Salient Stimuli

Abstract

SUMMARY Motivational states consist of cognitive, emotional, and physiological components controlled by multiple brain regions. An integral component of this neural circuitry is the bed nucleus of the stria terminalis (BNST). Here, we identify that neurons within BNST that express the gene prepronociceptin ( Pnoc BNST ) modulate rapid changes in physiological arousal that occur upon exposure to motivationally salient stimuli. Using in vivo two-photon calcium imaging, we find that Pnoc BNST neuronal responses directly correspond with rapid increases in pupillary size when mice are exposed to aversive and rewarding odors. Furthermore, optogenetic activation of these neurons increases pupillary size and anxiety-like behaviors but does not induce approach, avoidance, or locomotion. These findings suggest that excitatory responses in Pnoc BNST neurons encode rapid arousal responses that modulate anxiety states. Further histological, electrophysiological, and single-cell RNA sequencing data reveal that Pnoc BNST neurons are composed of genetically and anatomically identifiable subpopulations that may differentially tune rapid arousal responses to motivational stimuli.

Extended amygdala-parabrachial circuits alter threat assessment and regulate feeding

“…BNST vGLUT2 -PBN neurons are enriched in Adcyap1, which encodes the neuropeptide pituitary adenylate cyclase-activating peptide (PACAP), previously identified as a major regulator of stress responses in the BNST (30,31), including in contexts of addiction and posttraumatic stress disorder (32,33). Both BNST vGAT -PBN and BNST vGLUT2 -PBN neurons express calcitonin receptor (Calcr), recently associated with the regulation of feeding (34,35), and nociceptin (Pnoc), linked to motivated behaviors including feeding (24,(36)(37)(38). We further validated these RNA sequencing (RNA-seq) findings by performing fluorescent in situ hybridization experiments, which revealed coexpression of Tac2, Sstr3, and Calcr with vGAT and Adcyap1 with vGLUT2 neurons within the BNST ( fig.…”

The Subcortical-Allocortical- Neocortical continuum for the Emergence and Morphological Heterogeneity of Pyramidal Neurons in the Human Brain

“…The MeA subnuclei are involved with the (1) interpretation of environmental cues of conspecific stimuli; (2) processing of multiple sensory information, including direct and indirect olfactory and vomeronasal inputs with social relevance; (3) cellular responses to neural gonadal steroid actions for neuroendocrine secretion; and (4) modulation of reproductive and other social behaviors in rodents (Newman, 1999;Meredith and Westberry, 2004;Choi et al, 2005;Pro-Sistiaga et al, 2007;Rasia-Filho et al, 2012a,b;Petrulis et al, 2017;Petrulis, 2020). Being part of an organized neural network that projects to the bed nucleus of the stria terminalis (see relevant data on arousal behavior in Rodriguez-Romaguera et al, 2020) and to various hypothalamic and brainstem nuclei, the CeA and MeA subnuclei also participate in social and defensive reactions against innate and learned threats with neuroendocrine, behavioral, and sympathetic/parasympathetic responses to fearful and stressful stimuli (Davis, 1992;LeDoux, 1992;Quirk et al, 1995;Dayas et al, 1999;Rasia-Filho et al, 2000, 2012bPetrovich et al, 2001;Marcuzzo et al, 2007;Neckel et al, 2012;Petrulis, 2020;Anilkumar et al, 2021). In humans, the extended amygdala responds to the emotional salience of positive and negative affect (Liberzon et al, 2003).…”

PNOC Expressed by B Cells in Cholangiocarcinoma Was Survival Related and LAIR2 Could Be a T Cell Exhaustion Biomarker in Tumor Microenvironment: Characterization of Immune Microenvironment Combining Single-Cell and Bulk Sequencing Technology

“…In our analysis, we used bulk sequencing data of cholangiocarcinoma patients in TCGA database to calculate the immune infiltration scores of different immune cell populations, and then we compared expression difference between groups, locating immune infiltration highly associated genes; we found PNOC was mainly expressed by infiltrated B cells, which was survival related, while LAIR2 was mainly expressed by Tregs and partial CD8+/GZMB+ T cells, indicating exhaustive immune status of T cells. Prepronociceptin (PNOC) was formerly reported to be a preprotein for a series of products, which act as pain regulators in signal transduction (38). Recent study showed PNOC is involved in long-term opioid response, alcoholic states, and inflammation process (39)(40)(41)(42)(43)(44).…”