Design of a Trichromatic Cone Array

Cones with peak sensitivity to light at long (L), medium (M) and short (S) wavelengths are unequal in number on the human retina: S cones are rare (<10%) while increasing in fraction from center to periphery, and the L/M cone proportions are highly variable between individuals. What optical properties of the eye, and statistical properties of natural scenes, might drive this organization? We found that the spatial-chromatic structure of natural scenes was largely symmetric between the L, M and S sensitivity bands. Given this symmetry, short wavelength attenuation by ocular media gave L/M cones a modest signal-to-noise advantage, which was amplified, especially in the denser central retina, by long-wavelength accommodation of the lens. Meanwhile, total information represented by the cone mosaic remained relatively insensitive to L/M proportions. Thus, the observed cone array design along with a long-wavelength accommodated lens provides a selective advantage: it is maximally informative

The role of hypothalamic H1 receptor antagonism in antipsychotic-induced weight gain

Treatment with second generation antipsychotics (SGAs), notably olanzapine and clozapine, causes severe obesity side effects. Antagonism of histamine H1 receptors has been identified as a main cause of SGA-induced obesity, but the molecular mechanisms associated with this antagonism in different stages of SGA-induced weight gain remain unclear. This review aims to explore the potential role of hypothalamic histamine H1 receptors in different stages of SGA-induced weight gain/obesity and the molecular pathways related to SGA-induced antagonism of these receptors. Initial data have demonstrated the importance of hypothalamic H1 receptors in both short- and long-term SGA-induced obesity. Blocking hypothalamic H1 receptors by SGAs activates AMP-activated protein kinase (AMPK), a well-known feeding regulator. During short-term treatment, hypothalamic H1 receptor antagonism by SGAs may activate the AMPK—carnitine palmitoyltransferase 1 signaling to rapidly increase caloric intake and result in weight gain. During long-term SGA treatment, hypothalamic H1 receptor antagonism can reduce thermogenesis, possibly by inhibiting the sympathetic outflows to the brainstem rostral raphe pallidus and rostral ventrolateral medulla, therefore decreasing brown adipose tissue thermogenesis. Additionally, blocking of hypothalamic H1 receptors by SGAs may also contribute to fat accumulation by decreasing lipolysis but increasing lipogenesis in white adipose tissue. In summary, antagonism of hypothalamic H1 receptors by SGAs may time-dependently affect the hypothalamus-brainstem circuits to cause weight gain by stimulating appetite and fat accumulation but reducing energy expenditure. The H1 receptor and its downstream signaling molecules could be valuable targets for the design of new compounds for treating SGA-induced weight gain/obesity

New insights into energy and protein homeostasis by the kidney

Nephrolog

Retinal lateral inhibition provides the biological basis of long-range spatial induction

Retinal lateral inhibition is one of the conventional efficient coding mechanisms in the visual system that is produced by interneurons that pool signals over a neighborhood of presynaptic feedforward cells and send inhibitory signals back to them. Thus, the receptive-field (RF) of a retinal ganglion cell has a center-surround receptive-field (RF) profile that is classically represented as a difference-of-Gaussian (DOG) adequate for efficient spatial contrast coding. The DOG RF profile has been attributed to produce the psychophysical phenomena of brightness induction, in which the perceived brightness of an object is affected by that of its vicinity, either shifting away from it (brightness contrast) or becoming more similar to it (brightness assimilation) depending on the size of the surfaces surrounding the object. While brightness contrast can be modeled using a DOG with a narrow surround, brightness assimilation requires a wide suppressive surround. Early retinal studies determined that the suppressive surround of a retinal ganglion cell is narrow ( 500–1000 μm). In the current study, we examine the effect of this wide interneuron RF component in two biophysical retinal models and show that for both of the retinal models it explains the long-range effect evidenced in simultaneous brightness induction phenomena and that the spatial extent of this long-range effect of the retinal model responses matches that of perceptual data. These results suggest that the retinal lateral inhibition mechanism alone can regulate local as well as long-range spatial induction through the narrow and wide RF components of retinal interneurons, arguing against the existing view that spatial induction is operated by two separate local vs. long-range mechanisms.This work was supported by the European Research Council, Starting Grant ref. 306337, by the Spanish government and FEDER Fund, grant ref. TIN2015-71537-P(MINECO/FEDER,UE), and by the Icrea Academia Award