Ventromedial nucleus

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The ventromedial nucleus (VMN) of the hypothalamus is a large aggregation of neurones in the mediobasal hypothalamus adjacent to the third ventricle, bordered ventrally by the arcuate nucleus, laterally by the lateral hypothalamus, and dorsally by the dorsomedial nucleus. The VMN comprises mainly glutamatergic neurones, and it is involved in the regulation of feeding behaviour and glucose homeostasis [1], sexual behaviour and aggression. Lesions of the VMN result in obesity driven by excessive food intake, indicating that it has an important role in satiety.

Several appetite-inhibiting peptides are expressed in the VMN, including brain derived neurotrophic factor (BDNF) [2] and pituitary adenylate cyclase-activating polypeptide (PACAP), and this region is directly affected by appetite-stimulating factors ghrelin [3] and orexin-A, and by the appetite-inhibiting hormone leptin [4] In recent years, research on the contribution of the VMN to energy homeostasis has focused on VMN neurones that express the transcription factor steroidogenic factor 1 (SF1), which is essential for its development [5] In the mouse, the VMN is the only site of SF1 expression in the hypothalamus, and the knock out of SF1 in mice results in abnormal VMN development, and in late-onset obesity[6][7]. Since this discovery, several reports have linked SF1 neurones with leptin signalling,[8] with glucose homeostasis , and with the regulation of expression of cannabinoid receptor 1 (CBR1) [9] and BDNF. The expression of SF1 delineates the dorsal and central regions of the VMN.


The VMN can be subdivided into dorsomedial, central, and ventrolateral regions based on the expression of transcription factors, receptors, and neuropeptides. [10]. This nucleus is also electrophysiological heterogeneous, containing several subpopulations of cells that differ in their spontaneous discharge characteristics and in their responses to various stimuli.

In the control of satiety, the VMN is a likely target for another appetite-inhibiting factor, the centrally-released peptide oxytocin. I.c.v. injection of oxytocin agonists potently inhibits food intake, and these effects are prevented by oxytocin antagonists. Within the brain, oxytocin is released from centrally-projecting parvocellular neurons of the paraventricular nucleus (PVN), and from the soma and dendrites of magnocellular neurons of the PVN and supraoptic nucleus. Both of these populations are activated during feeding, and by appetite-inhibitor peptide glucagon-like peptide 1 (GLP-1). The VMN is a site of exceptionally dense expression of oxytocin receptors. , particularly in the ventrolateral VMN. Oxytocin receptors in the VMN are involved in sexual behaviour in female rats [11] where they are regulated by estrogen, as well as in appetite regulation.[12]

References

  1. King BM (2006) The rise, fall, and resurrection of the ventromedial hypothalamus in the regulation of feeding behavior and body weight Physiol Behav 87:221-44
  2. Conner JM et al. (1997) Distribution of brain-derived neurotrophic factor (BDNF) protein and mRNA in the normal adult rat CNS: evidence for anterograde axonal transport J Neurosci 17:2295-313
  3. Chen X et al. (2005) Effects of ghrelin on hypothalamic glucose responding neurons in rats. Brain Res 1055: 131-6
  4. Bingham NC et al. (2008) Selective loss of leptin receptors in the ventromedial hypothalamic nucleus results in increased adiposity and a metabolic syndrome. Endocrinology 149:2138-48
  5. Ikeda Y et al. The nuclear receptor steroidogenic factor 1 is essential for the formation of the ventromedial hypothalamic nucleus Mol Endocrinol 9:478-86
  6. Majdic G et al. (2002) Knockout mice lacking steroidogenic factor 1 are a novel genetic model of hypothalamic obesity. Endocrinology 143:607-14
  7. Tran PV et al. (2003) Requirement of the orphan nuclear receptor SF-1 in terminal differentiation of ventromedial hypothalamic neurons. Mol Cell Neurosci 22:441-53
  8. Dhillon H et al. (2006) Leptin directly activates SF1 neurons in the VMH, and this action by leptin is required for normal body-weight homeostasis. Neuron 2006. 49:191-203
  9. Kim KW et al. (2008) Steroidogenic factor 1 regulates expression of the cannabinoid receptor 1 in the ventromedial hypothalamic nucleus. Mol Endocrinol 22:1950-61
  10. Millhouse OE (1973) The organization of the ventromedial hypothalamic nucleus. Brain Res 55:1-87
  11. McCarthy MM et al. (1994) Infusion of antisense oligodeoxynucleotides to the oxytocin receptor in the ventromedial hypothalamus reduces estrogen-induced sexual receptivity and oxytocin receptor binding in the female rat. Neuroendocrinology 59:432-40
  12. Bale TL, Dorsa DM (1995) Regulation of oxytocin receptor messenger ribonucleic acid in the ventromedial hypothalamus by testosterone and its metabolites. Endocrinology, 1995. 136:5135-8