资源环境科技发展态势分析平台

Animals sense the environment through pathways that link sensory organs to the brain. In the visual system, these feedforward pathways define the classical feedforward receptive field (ffRF), the area in space in which visual stimuli excite a neuron(1). The visual system also uses visual context-the visual scene surrounding a stimulus-to predict the content of the stimulus(2), and accordingly, neurons have been identified that are excited by stimuli outside their ffRF(3-8). However, the mechanisms that generate excitation to stimuli outside the ffRF are unclear. Here we show that feedback projections onto excitatory neurons in the mouse primary visual cortex generate a second receptive field that is driven by stimuli outside the ffRF. The stimulation of this feedback receptive field (fbRF) elicits responses that are slower and are delayed in comparison with those resulting from the stimulation of the ffRF. These responses are preferentially reduced by anaesthesia and by silencing higher visual areas. Feedback inputs from higher visual areas have scattered receptive fields relative to their putative targets in the primary visual cortex, which enables the generation of the fbRF. Neurons with fbRFs are located in cortical layers that receive strong feedback projections and are absent in the main input layer, which is consistent with a laminar processing hierarchy. The observation that large, uniform stimuli-which cover both the fbRF and the ffRF-suppress these responses indicates that the fbRF and the ffRF are mutually antagonistic. Whereas somatostatin-expressing inhibitory neurons are driven by these large stimuli, inhibitory neurons that express parvalbumin and vasoactive intestinal peptide have mutually antagonistic fbRF and ffRF, similar to excitatory neurons. Feedback projections may therefore enable neurons to use context to estimate information that is missing from the ffRF and to report differences in stimulus features across visual space, regardless of whether excitation occurs inside or outside the ffRF. By complementing the ffRF, the fbRF that we identify here could contribute to predictive processing.

Feedback projections onto neurons of the mouse primary visual cortex generate a second excitatory receptive field that is driven by stimuli outside of the classical feedforward receptive field, with responses mediated by higher visual areas.

Although it is well-established that reductions in the ratio of insulin to glucagon in the portal vein have a major role in the dysregulation of hepatic glucose metabolism in type-2 diabetes(1-3), the mechanisms by which glucagon affects hepatic glucose production and mitochondrial oxidation are poorly understood. Here we show that glucagon stimulates hepatic gluconeogenesis by increasing the activity of hepatic adipose triglyceride lipase, intrahepatic lipolysis, hepatic acetyl-CoA content and pyruvate carboxylase flux, while also increasing mitochondrial fat oxidation-all of which are mediated by stimulation of the inositol triphosphate receptor 1 (INSP3R1). In rats and mice, chronic physiological increases in plasma glucagon concentrations increased mitochondrial oxidation of fat in the liver and reversed diet-induced hepatic steatosis and insulin resistance. However, these effects of chronic glucagon treatment-reversing hepatic steatosis and glucose intolerance-were abrogated in Insp3r1 (also known as Itpr1)-knockout mice. These results provide insights into glucagon biology and suggest that INSP3R1 may represent a target for therapies that aim to reverse nonalcoholic fatty liver disease and type-2 diabetes.