Somatostatin interneurons delineate the inner part of the external plexiform layer in the mouse main olfactory bulb

International audienceNeuropeptides play a major role in the modulation of information processing in neural networks. Somatostatin, one of the most concentrated neuropeptides in the brain, is found in many sensory systems including the olfactory pathway. However, its cellular distribution in the mouse main olfactory bulb (MOB) is yet to be characterized. Here we show that approximately 95% of mouse bulbar somatostatin-immunoreactive (SRIF-ir) cells describe a homogeneous population of interneurons. These are restricted to the inner lamina of the external plexiform layer (iEPL) with dendritic field strictly confined to the region. iEPL SRIF-ir neurons share some morphological features of Van Gehuchten short-axon cells, and always express glutamic acid decarboxylase, calretinin, and vasoactive intestinal peptide. One-half of SRIF-ir neurons are parvalbumin-ir, revealing an atypical neurochemical profile when compared to SRIF-ir interneurons of other forebrain regions such as cortex or hippocampus. Somatostatin is also present in fibers and in a few sparse presumptive deep short-axon cells in the granule cell layer (GCL), which were previously reported in other mammalian species. The spatial distribution of somatostatin interneurons in the MOB iEPL clearly outlines the region where lateral dendrites of mitral cells interact with GCL inhibitory interneurons through dendrodendritic reciprocal synapses. Symmetrical and asymmetrical synaptic contacts occur between SRIF-ir dendrites and mitral cell dendrites. Such restricted localization of somatostatin interneurons and connectivity in the bulbar synaptic network strongly suggest that the peptide plays a functional role in the modulation of olfactory processing

Sexually dimorphic distribution of sst2A receptors on growth hormone-releasing hormone neurones in mice: modulation by gonadal steroids.: steroids and sst2A receptors on GHRH neurones

International audienceThe ultradian pulsatile pattern of growth hormone (GH) secretion is markedly sexually dimorphic in rodents as in primates, but the neuroanatomical mechanisms of this phenomenon are not clear. In the arcuate nucleus of the hypothalamus, GH-releasing hormone (GHRH) neurones receive somatostatinergic inputs through the sst2A receptor (sst2A-R) and the percentage of GHRH neurones bearing sst2A-R is higher in female than in male GHRH-enhanced green fluorescent protein (eGFP) mice. In the present study, we hypothesised that sst2A-R expression on GHRH neurones is modulated by gonadal steroids and constitutes a mechanism for sexually differentiated GH secretion. The distribution of sst2A-R on GHRH neurones was evaluated by immunohistochemistry in adult GHRH-eGFP mice gonadectomised and treated for 3 weeks with oestradiol or testosterone implants. In gonadectomised females supplemented with testosterone, sst2A-R distribution on GHRH neurones was reduced to the level seen in intact males, whereas oestradiol implants were ineffective. Conversely, orchidectomy induced a female 'sst2A phenotype', which was reversed by testosterone supplementation. Changes in the hepatic expression of GH-dependent genes for major urinary protein-3 and the prolactin receptor reflected the altered steroid influence on GH pulsatile secretion. In the ventromedial-arcuate region, GHRH and sst2-R, as well as GHRH and somatostatin expression as measured by the real-time polymerase chain reaction, were positively correlated in both sexes. By contrast, the positive correlation between ventromedial-arcuate GHRH and periventricular somatostatin expression in males was reversed to a negative one in females. Moreover, the positive correlation between periventricular somatostatin and ventromedial-arcuate sst2-R expressions in males was lost in females. These results suggest that, in the adult mouse, testosterone is a major modulator of sst2A distribution on GHRH neurones. This marked sex difference in sst2A-R distribution may constitute a key element in the genesis of the sexually differentiated pattern of GH secretion, possibly through testosterone-modulated changes in somatostatin inputs from hypophysiotrophic periventricular neurones

Role of the ghrelin/obestatin balance in the regulation of neuroendocrine circuits controlling body composition and energy homeostasis

Ghrelin and obestatin are two peptides isolated from the gastrointestinal tract and encoded by the same preproghrelin gene. They convey to the central nervous system informations concerning the nutritional status and/or the energy stores. Ghrelin, mostly acting through the GH secretagogue receptor GHS-R, is a potent GH secretagogue, an orexigenic peptide and a long-term regulator of energy homeostasis. Obestatin was initially described for its anorexigenic effects and its binding to the G protein-coupled receptor 39 (GPR39). However, the role of obestatin is still controversial and the nature of the obestatin receptor remains an open question. This review is focussed on the possible implication of the ghrelin/obestatin system in psychiatric diseases with particular emphasis on eating disorders

Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism.

International audienceMutations that decrease insulin-like growth factor (IGF) and growth hormone signaling limit body size and prolong lifespan in mice. In vertebrates, these somatotropic hormones are controlled by the neuroendocrine brain. Hormone-like regulations discovered in nematodes and flies suggest that IGF signals in the nervous system can determine lifespan, but it is unknown whether this applies to higher organisms. Using conditional mutagenesis in the mouse, we show that brain IGF receptors (IGF-1R) efficiently regulate somatotropic development. Partial inactivation of IGF-1R in the embryonic brain selectively inhibited GH and IGF-I pathways after birth. This caused growth retardation, smaller adult size, and metabolic alterations, and led to delayed mortality and longer mean lifespan. Thus, early changes in neuroendocrine development can durably modify the life trajectory in mammals. The underlying mechanism appears to be an adaptive plasticity of somatotropic functions allowing individuals to decelerate growth and preserve resources, and thereby improve fitness in challenging environments. Our results also suggest that tonic somatotropic signaling entails the risk of shortened lifespan