Neural Connectivity in the Mediobasal Hypothalamus of the Sheep Brain

Abstract

The ventromedial nucleus of the hypothalamus (VMN) and the arcuate nucleus (ARC) are two centres regulating energy balance and food intake, but inter-connectivity of these nuclei is not well defined in non-rodent species. In this study, we performed retrograde tracing and immunohistochemistry in the ovine brain with ewes receiving FluoroGold® (FG) injections into either ARC or VMN for the mapping of retrogradely labelled cells. Strong reciprocal connections were found between the two regions. The distribution of the FG labelled neurons in other regions of the hypothalamus and brain stem was also mapped. Some of the cells projecting from ARC to VMN were immunopositive for neuropeptide Y, galanin, adrenocorticotropin (marker of pro-opiomelanocortin cells) or tyrosine hydroxylase (marker of dopaminergic cells). Melanin-concentrating hormone and orexin neurons in the lateral hypothalamic area were also found to provide input to the VMN and ARC. This observed interconnectivity between regions important for metabolic regulation and other neuroendocrine functions presumably allows coordinated functions. Input to both the ARC and VMN from other brain regions, such as brain stem cell groups, provides a further level of regulation. These data provide a substrate upon which further understanding of appetite regulation and neuroendocrine function can be derived in this species.

MRI Techniques and New Animal Models for Imaging the Brain

“…in pigs, Kanitz et al 2003, Loijens et al 2002, Piekarzewska et al 1999, Piekarzewska et al 2000, Zanella et al 1996 have demonstrated the involvement of neuropeptides such as CRF and enkephalins in different brain areas including the hypothalamus, brainstem and cortices. While neuroanatomical methods have been used to describe the immunoreactive content of brain areas (in sheep: Tillet 1995; in pigs: Kineman et al 1989, Leshin et al 1996, Niblock et al 2005, Rowniak et al 2008; in large mammals: Tillet & Kitahama, 1998), and neuronaltracing methods have been used to describe the interconnections between some of these brain areas (sheep: Qi et al 2008, Rivalland et al 2006, Tillet et al 1993pigs: Chaillou et al 2009), no dynamic functional information is available about the functional interactions among these different factors. The use of MRI techniques could be an interesting way of gaining a better understanding of the neuronal circuits of animal emotion and other functions.…”

Selected hormonal and neurotransmitter mechanisms regulating feed intake in sheep

“…The receptor for orexin (OX1R) was localized to the ARC, median eminence, lateral hypothalamic nuclei and ventral portion of the preoptic area (Zhang et al, 2005). Interestingly, ORX neurons originating in the LHA provide input to both the ARC and VMN (Qi et al, 2008). Combined, these studies link ORX to regions of the hypothalamus related to feed intake, endocrine, metabolic and reproductive regulation.…”

“…In colchicine-treated sheep, NPY neurons were found distributed between two populations of cells within the ARC, median eminence, pituitary stalk, the dorsomedian and dorsocaudal nuclei, and in the periventricular nucleus (PeVN; Polkowska et al, 2006a), but were absent in the magnocellular neurons of the paraventricular and supraoptic nuclei (Chaillou et al, 2002;Chaillou and Tillet, 2005). There is also a rich interconnection between the ARC and VMN in sheep (Qi et al, 2008). In addition, numerous studies have demonstrated expression of NPY mRNA in the ARC Adam et al, 2002;Pillon et al, 2003).…”

“…Orexin ORX expression has been demonstrated in neurons of the LHA (Iqbal et al, 2001c;Qi et al, 2008) as well as the dorsomedial nucleus, zona incerta, perifornical area and anterior hypothalamic area (Iqbal et al, 2001c). The receptor for orexin (OX1R) was localized to the ARC, median eminence, lateral hypothalamic nuclei and ventral portion of the preoptic area (Zhang et al, 2005).…”

“…In sheep, MCH has been found to be localized to the supramammillary nucleus, nucleus medialis thalami and nucleus reunions (Tillet et al, 1996). Of further interest are studies which indicate that MCH neurons from the LHA provide input to the ARC and VMN (Qi et al, 2008). This adds a possible layer of reciprocal control of appetite, metabolic and endocrine control within the hypothalamus.…”