RESUMEN
Activation of prepronociceptin (PNOC)-expressing neurons in the arcuate nucleus (ARC) promotes high-fat-diet (HFD)-induced hyperphagia. In turn, PNOCARC neurons can inhibit the anorexic response of proopiomelanocortin (POMC) neurons. Here, we validate the necessity of PNOCARC activity for HFD-induced inhibition of POMC neurons in mice and find that PNOCARC-neuron-dependent inhibition of POMC neurons is mediated by gamma-aminobutyric acid (GABA) release. When monitoring individual PNOCARC neuron activity via Ca2+ imaging, we find a subpopulation of PNOCARC neurons that is inhibited upon gastrointestinal calorie sensing and disinhibited upon HFD feeding. Combining retrograde rabies tracing and circuit mapping, we find that PNOC neurons from the bed nucleus of the stria terminalis (PNOCBNST) provide inhibitory input to PNOCARC neurons, and this inhibitory input is blunted upon HFD feeding. This work sheds light on how an increase in caloric content of the diet can rewire a neuronal circuit, paving the way to overconsumption and obesity development.
Asunto(s)
Dieta Alta en Grasa , Hiperfagia , Núcleos Septales , Animales , Hiperfagia/metabolismo , Ratones , Núcleos Septales/metabolismo , Neuronas/metabolismo , Masculino , Ácido gamma-Aminobutírico/metabolismo , Proopiomelanocortina/metabolismo , Neuronas GABAérgicas/metabolismo , Núcleo Arqueado del Hipotálamo/metabolismo , Ratones Endogámicos C57BL , Precursores de Proteínas , Receptores OpioidesRESUMEN
Stress is a risk factor for emotion and energy metabolism disorders. However, the neurocircuitry mechanisms for emotion initiation and glucose mobilization underlying stress responses are unclear. Here we demonstrate that photoactivation of Gad2+ projection from the anterior bed nucleus of the stria terminalis (aBNST) to the arcuate nucleus (ARC) induces anxiety-like behavior as well as acute hyperglycemia. Photoinhibition of the circuit is anxiolytic and blocks hyperglycemia induced by restraint stress. Pharmacogenetic inhibition of the ARCGad2+âraphe obscurus nucleus (ROb) and photoactivation of the aBNSTGad2+âARC circuits simultaneously leads to significant hypoglycemia and anxiety-like behavior. Pharmacogenetic inhibition of the ARCGad2+ânucleus of the solitary tract (NTS) whilst photoactivation of the aBNSTGad2+âARC circuit only induces hyperglycemia. Our results reveal that the aBNSTGad2+âARCGad2+âROb circuit is recruited for the stress response of rapid glucose mobilization and the aBNSTGad2+âARCGad2+âNTS circuit for behavioral symptoms of stress response. This study identifies a possible general strategy for neurocircuitry structural organization dealing with multiple organs involved in responses, with potential therapeutic targets for emotion and energy metabolism disorders underlying psychiatric disorders.
Asunto(s)
Hiperglucemia , Núcleos Septales , Humanos , Glucosa/metabolismo , Núcleos Septales/fisiología , Ansiedad/metabolismo , Núcleo Arqueado del Hipotálamo , Hiperglucemia/metabolismoRESUMEN
Previous work have shown several key brain nuclei involved in acute psychological stress and glucose homeostasis. Acute stress influences glucose metabolism via released stress hormones by activating the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Little is known about the brain nuclei which response to peripheral glucose alteration are either abundant with glucosesensing neurons or the activations are secondary to stress. Here we profile and compare the brain nuclei that response to stress and glucose homeostasis in mouse models of acute restraint stress, glucose and 2-DG injections respectively. Our present work provide a comprehensive depiction on key brain nuclei involved in CNS control of stress and glucose homeostasis, which gives clue for functional identification of brain nuclei that regulate glucose homeostasis under stress.
Asunto(s)
Encéfalo/fisiología , Glucosa/metabolismo , Homeostasis , Neuronas/fisiología , Estrés Psicológico/fisiopatología , Animales , Encéfalo/citología , Sistema Hipotálamo-Hipofisario/metabolismo , Ratones , Sistema Hipófiso-Suprarrenal/metabolismo , Sistema Nervioso Simpático/metabolismoRESUMEN
Sensory cortices process stimuli in manners essential for perception. Very little is known regarding interactions between olfactory cortices. The piriform "primary" olfactory cortex, especially its anterior division (aPCX), extends dense association fibers into the ventral striatum's olfactory tubercle (OT), yet whether this corticostriatal pathway is capable of shaping OT activity, including odor-evoked activity, is unknown. Further unresolved is the synaptic circuitry and the spatial localization of OT-innervating PCX neurons. Here we build upon standing literature to provide some answers to these questions through studies in mice of both sexes. First, we recorded the activity of OT neurons in awake mice while optically stimulating principal neurons in the aPCX and/or their association fibers in the OT while the mice were delivered odors. This uncovered evidence that PCX input indeed influences OT unit activity. We then used patch-clamp recordings and viral tracing to determine the connectivity of aPCX neurons upon OT neurons expressing dopamine receptor types D1 or D2, two prominent cell populations in the OT. These investigations uncovered that both populations of neurons receive monosynaptic inputs from aPCX glutamatergic neurons. Interestingly, this input originates largely from the ventrocaudal aPCX. These results shed light on some of the basic physiological properties of this pathway and the cell-types involved and provide a foundation for future studies to identify, among other things, whether this pathway has implications for perception.SIGNIFICANCE STATEMENT Sensory cortices interact to process stimuli in manners considered essential for perception. Very little is known regarding interactions between olfactory cortices. The present study sheds light on some of the basic physiological properties of a particular intercortical pathway in the olfactory system and provides a foundation for future studies to identify, among other things, whether this pathway has implications for perception.