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20. Constitutive and conditional deletion reveals distinct phenotypes driven by developmental versus neurotransmitter actions of the neuropeptide PACAP.

Author

Bakalar, Dana, Gavrilova, Oksana, Jiang, Sunny Z., Zhang, Hai‐ying, Roy, Snehashis, Williams, Sarah K., Liu, Naili, Wisser, Stephen, Usdin, Ted B., and Eiden, Lee E.

Subjects
PITUITARY adenylate cyclase activating polypeptide, NEURAL development, KNOCKOUT mice, CENTRAL nervous system, PEPTIDES
Abstract

Neuropeptides may exert trophic effects during development, and then neurotransmitter roles in the developed nervous system. One way to associate peptide‐deficiency phenotypes with either role is first to assess potential phenotypes in so‐called constitutive knockout mice, and then proceed to specify, regionally and temporally, where and when neuropeptide expression is required to prevent these phenotypes. We have previously demonstrated that the well‐known constellation of behavioral and metabolic phenotypes associated with constitutive pituitary adenylate cyclase‐activating peptide (PACAP) knockout mice are accompanied by transcriptomic alterations of two types: those that distinguish the PACAP‐null phenotype from wild‐type (WT) in otherwise quiescent mice (cPRGs), and gene induction that occurs in response to acute environmental perturbation in WT mice that do not occur in knockout mice (aPRGs). Comparing constitutive PACAP knockout mice to a variety of temporally and regionally specific PACAP knockouts, we show that the prominent hyperlocomotor phenotype is a consequence of early loss of PACAP expression, is associated with Fos overexpression in hippocampus and basal ganglia, and that a thermoregulatory effect previously shown to be mediated by PACAP‐expressing neurons of medial preoptic hypothalamus is independent of PACAP expression in those neurons in adult mice. In contrast, PACAP dependence of weight loss/hypophagia triggered by restraint stress, seen in constitutive PACAP knockout mice, is phenocopied in mice in which PACAP is deleted after neuronal differentiation. Our results imply that PACAP has a prominent role as a trophic factor early in development determining global central nervous system characteristics, and in addition a second, discrete set of functions as a neurotransmitter in the fully developed nervous system that support physiological and psychological responses to stress. [ABSTRACT FROM AUTHOR]

Published
2023
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21. Nucleus of the lateral olfactory tract: A hub linking the water homeostasis‐associated supraoptic nucleus‐arginine vasopressin circuit and neocortical regions to promote social behavior under osmotic challenge.

Author

Hernández‐Pérez, Oscar R., Hernández, Vito S., Zetter, Mario A., Eiden, Lee E., and Zhang, Limei

Subjects
PITUITARY adenylate cyclase activating polypeptide, GLUTAMATE transporters, PREOPTIC area, VASOPRESSIN, TEMPOROPARIETAL junction, SOCIAL interaction, IN situ hybridization
Abstract

Homeostatic challenges may alter the drive for social interaction. The neural activity that prompts this motivation remains poorly understood. In the present study, we identify direct projections from the hypothalamic supraoptic nucleus to the cortico‐amygdalar nucleus of the lateral olfactory tract (NLOT). Dual in situ hybridization with probes for pituitary adenylate cyclase‐activating polypeptide (PACAP), as well as vesicular glutamate transporter (VGLUT)1, VGLUT2, V1a and V1b, revealed a population of vasopressin‐receptive PACAPergic neurons in NLOT layer 2 (NLOT2). Water deprivation (48 h, WD48) increased sociability compared to euhydrated subjects, as assessed with the three‐chamber social interaction test (3CST). Fos expression immunohistochemistry showed NLOT and its main efferent regions had further increases in rats subjected to WD48 + 3CST. These regions strongly expressed PAC1 mRNA. Microinjections of arginine vasopressin (AVP) into the NLOT produced similar changes in sociability to water deprivation, and these were reduced by co‐injection of V1a or V1b antagonists along with AVP. We conclude that, during challenge to water homeostasis, there is a recruitment of a glutamatergic‐multi‐peptidergic cooperative circuit that promotes social behavior. [ABSTRACT FROM AUTHOR]

Published
2023
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