Figure 5 Model of NO volume transmission in

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Figure 5 Model of NO volume transmission in the preoptic region and its impact on GnRH neuronal function Figure 5 | Model of NO volume transmission in the preoptic region and its impact on GnRH neuronal function. a | The homeostatic status of the individual is shown. b | Computed profiles of steady-state nitric oxide (NO) concentrations across the centre of a cubic array of spherical surface sources are shown. Spheres of radius 7.5 µm and numbering 125 (left panel), 343 (middle panel) and 729 (right panel) are illustrated in 3D arrays within a fixed volume. The upper panels illustrate the distribution of NO within and outside the area of production, and the traces below (blue lines) indicate sample concentrations taken through the centre of each array (marked by arrows in the left upper panel). The spheres generate NO at their surface at a rate of 40 molecules per s (the resultant NO concentrations throughout the array at steady state are calculated as described elsewhere150, assuming a rate constant for NO inactivation of 100 s−1). According to the physiological (or pathological) conditions, the numbers of active NO neurons can vary from sparse, when concentrations of NO between the source are near zero (left panel), to intermediate abundance, when only low levels of NO are present intercellularly (middle panel), to abundant, when NO builds up to nanomolar concentrations throughout the tissue volume, endowing NO with the capacity to act as a 'volume transmitter' able to influence gonadotropin-releasing hormone (GnRH) neurons (in the figure, indicated by '1', '2' and '3') located at a distance (right panel). c | Hypothetical changes in the firing of GnRH neurons identified in part b according to electrophysiological data detailed elsewhere82 on the effect of NO on GnRH neuronal activity in living brain slices are shown. d | The hypothalamic–pituitary–gonadal axis outcomes are shown. Chachlaki, K. et al. (2017) The gentle art of saying NO: how nitric oxide gets things done in the hypothalamus Nat. Rev. Endocrinol. doi:10.1038/nrendo.2017.69