ABSTRACT
In the face of starvation, animals will engage in high-risk behaviors that would normally be considered maladaptive. Starving rodents, for example, will forage in areas that are more susceptible to predators and will also modulate aggressive behavior within a territory of limited or depleted nutrients. The neural basis of these adaptive behaviors likely involves circuits that link innate feeding, aggression and fear. Hypothalamic agouti-related peptide (AgRP)-expressing neurons are critically important for driving feeding and project axons to brain regions implicated in aggression and fear. Using circuit-mapping techniques in mice, we define a disynaptic network originating from a subset of AgRP neurons that project to the medial nucleus of the amygdala and then to the principal bed nucleus of the stria terminalis, which suppresses territorial aggression and reduces contextual fear. We propose that AgRP neurons serve as a master switch capable of coordinating behavioral decisions relative to internal state and environmental cues.
Subject(s)
Aggression/physiology , Agouti-Related Protein/physiology , Amygdala/physiology , Fear/physiology , Hypothalamus/physiology , Peptide Fragments/physiology , Septal Nuclei/physiology , Starvation/physiopathology , Agouti-Related Protein/metabolism , Amygdala/metabolism , Animals , Gene Knock-In Techniques , Hypothalamus/metabolism , Male , Mice , Neural Pathways/metabolism , Neural Pathways/physiology , Neurons/physiology , Peptide Fragments/metabolism , Septal Nuclei/metabolismABSTRACT
Hypothalamic neuronal populations are central regulators of energy homeostasis and reproductive function. However, the ontogeny of these critical hypothalamic neuronal populations is largely unknown. We developed a novel approach to examine the developmental pathways that link specific subtypes of neurons by combining embryonic and adult ribosome-tagging strategies in mice. This new method shows that Pomc-expressing precursors not only differentiate into discrete neuronal populations that mediate energy balance (POMC and AgRP neurons), but also into neurons critical for puberty onset and the regulation of reproductive function (Kiss1 neurons). These results demonstrate a developmental link between nutrient-sensing and reproductive neuropeptide synthesizing neuronal populations and suggest a potential pathway that could link maternal nutrition to reproductive development in the offspring.
Subject(s)
Gene Expression Regulation, Developmental/genetics , Hypothalamus/cytology , Kisspeptins/metabolism , Neurons/metabolism , Pro-Opiomelanocortin/metabolism , Stem Cells/physiology , Agouti-Related Protein/genetics , Agouti-Related Protein/metabolism , Animals , Dependovirus/genetics , Embryo, Mammalian , Genetic Vectors/physiology , Green Fluorescent Proteins/genetics , Green Fluorescent Proteins/metabolism , Immunoprecipitation , Kisspeptins/genetics , Mice , Mice, Inbred C57BL , Mice, Transgenic , Microarray Analysis , Pro-Opiomelanocortin/genetics , RNA, Messenger/metabolism , T-Box Domain Proteins/genetics , T-Box Domain Proteins/metabolismABSTRACT
A new molecule, the 4-methyl-thio-phenyl-propylamine (PrNH(2)) was synthesized and its biological interaction with different amine oxidases such as semicarbazide sensitive amine oxidase (SSAO) [E.C.1.4.3.6], and monoamine oxidase [E.C.1.4.3.4] under its two isoforms, MAO A and MAO B, has been assessed. The substrate specifities of MAO and SSAO overlap to some extent. In this context, the search of new molecules, able to discriminate between these different amine oxidases is very important as it will allow greater elucidation of the SSAO's role in physiological and pathological conditions. We report for the first time, the synthesis and evaluation of a new molecule which has a high affinity towards the SSAO family of enzymes, more so than previously described and furthermore an ability to discriminate between the different amine oxidases.