How does the lesser Egyptian Jerboa survive in the desert without drinking?

Whilst water balance is aggressively defended in all terrestrial animals, this is all the more so in those species (xerocoles) that thrive in the hot, arid conditions of the Arabian and North African deserts. The harsh environment of the desert is host to a remarkably diverse spectrum of adapted mammals, from the magnificent one-humped Arabian dromedary camel (Camelus dromedarius), to tiny rodents, such as the Lesser Egyptian Jerboa (Jaculus jaculus). In order to understand the physiological mechanisms that enable mammals to survive in arid regions, which, in turn, will teach us about biological adaptations to climate change, in this proposal we focus on the latter, more convenient, rodent model, Jerboas do not drink liquids as such, deriving all of their water from food, and they are able to survive prolonged periods of dehydration. Water economy is thus vital and, this is achieved by the production of a low volume of highly concentrated urine, as a consequence of the highly efficient reabsorption of water at the level of the kidney. This is mediated by the actions of the antidiuretic hormone arginine vasopressin (AVP), which is made in a specialised part of the brain called the hypothalamo-neurohypophysial system (HNS). The HNS consists of the large peptidergic magnocellular neurones (MCNs) of the hypothalamic supraoptic (SON) and paraventricular (PVN) nuclei, the axons of which course though the internal zone of the median eminence (ME) to terminations on blood capillaries of the posterior pituitary (PP) gland, a neuro-vascular interface through which the brain regulates peripheral organs in order to maintain homeostasis. The rise in plasma osmolality that follows dehydration is detected by intrinsic MCN mechanisms and by specialised osmoreceptive neurons in the circumventricular organs (CVOs) such as the subfornical organ (SFO), which provide excitatory inputs to shape the firing activity of MCNs for AVP secretion. Upon release, AVP travels through the blood to specific kidney receptors where it promotes water reabsorption in the collecting duct. Dehydration evokes a dramatic functional remodelling of the HNS, a process known as function-related plasticity. A plethora of activity-dependent changes in the morphology, electrical properties and biosynthetic and secretory activity of the HNS have been described, all of which might contribute to the facilitation of hormone production and delivery, and hence survival. We sought to understand this plasticity in terms of changes in global gene expression patterns. Thus, we used Affymetrix GeneChips, and latterly RNAseq, to document the transcriptomes of the rat and the mouse HNS, and to describe how these change following dehydration. Bioinformatic analysis was then used to identify nodal target genes, the functions of which were then investigated in vivo. We have developed viral gene deliver methods that enable us to manipulate the activity of specific endogenous genes within the HNS of the intact conscious rats. We can ask how this affect the physiology of the rat in terms of its response to dehydrating cues. We are applying this successful strategy to Jaculus jaculus in order to understand the physiological mechanisms that enable this species to survive in the desert without drinking. We will describe, at the molecular level, the response of the Jaculus jaculus HNS to chronic dehydration. Animals will be subjected to comprehensive physiological, morphological, transcriptomic and neuropeptidomic investigation. Datasets will be subject to bioinformatic analyses that will reveal target genes, the functions of which will be tested in vivo in our established rat models.