The retina encodes environmental light intensity to drive innate physiological responses. The synaptic basis of such coding remains obscure. Intrinsically photosensitive retinal ganglion cells (ipRGCs) are the only retinal output neurons stably encoding intensity. They do so even without their melanopsin photopigment, so specializations in their synaptic drive from bipolar cells (BCs) must also contribute. Here, we shed new light on mechanisms responsible for this unique intensity-coding drive. By ultrastructural reconstruction, we show that specific BC types and unusual ribbon synapses carry photoreceptor signals to ipRGCs. By glutamate imaging and electrophysiology, we show that their light responses are unusually persistent. Still, we find that virtually all BCs encode intensity. Intensity coding becomes restricted to ipRGCs primarily because other RGCs filter out steady-state intensity signals postsynaptically. Thus, neural 'pinholes' in global, persistent neural 'masking' allow intensity signals to be encoded by ipRGCs and sent to specific centers of the visual brain.

Background Low-carbohydrate, high animal fat and protein diets have been promoted for weight loss and diabetes treatment. We therefore tested the effect of a low-carbohydrate vegan diet in diabetes as a potentially healthier and more ecologically sustainable low-carbohydrate option. Objectives We sought to compare the effectiveness of a low-carbohydrate vegan diet with a moderate-carbohydrate vegetarian diet on weight loss and metabolic measures in diabetes. Methods One hundred and sixty-four male and female participants with type 2 diabetes were randomly assigned to advice on either a low-carbohydrate vegan diet, high in canola oil and plant proteins, or a vegetarian therapeutic diet, for 3 mo, with both diets recommended at 60% of calorie requirements. Body weight, fasting blood, blood pressure, and 7-d food records, to estimate potential greenhouse gas emissions, were obtained throughout the study with tests of cholesterol absorption undertaken at baseline and end of study on 50 participants. Results Both low-carbohydrate vegan and vegetarian diets similarly but markedly reduced body weight (−5.9 kg; 95% CI: −6.5, −5.28 kg; and −5.23 kg; 95% CI: −5.84, −4.62 kg), glycated hemoglobin (−0.99%; 95% CI: −1.07, −0.9%; and −0.88%; 95% CI: −0.97, −0.8%), systolic blood pressure (−4 mmHg; 95% CI: −7, −2 mmHg; and −6 mmHg; 95% CI: −8, −3 mmHg), and potential greenhouse gas emissions, but only for potential greenhouse gas emissions was there a significant treatment difference of −0.63 kgCO2/d (95% CI: −0.99, −0.27 kgCO2/d) favoring the low-carbohydrate vegan diet. Conclusions Low-carbohydrate vegan and vegetarian diets reduced body weight, improved glycemic control and blood pressure, but the more plant-based diet had greater potential reduction in greenhouse gas emissions. Trial registration number: clinicaltrials.gov identifier NCT02245399.

We have explored the synaptic networks responsible for the unique capacity of intrinsically photosensitive retinal ganglion cells (ipRGCs) to encode overall light intensity. This luminance signal is crucial for circadian, pupillary and related reflexive responses light. By combined glutamate-sensor imaging and patch recording of postsynaptic RGCs, we show that the capacity for intensity-encoding is widespread among cone bipolar types, including OFF types.Nonetheless, the bipolar cells that drive ipRGCs appear to carry the strongest luminance signal.By serial electron microscopic reconstruction, we show that Type 6 ON cone bipolar cells are the dominant source of such input, with more modest input from Types 7, 8 and 9 and virtually none from Types 5i, 5o, 5t or rod bipolar cells. In conventional RGCs, the excitatory drive from bipolar cells is high-pass temporally filtered more than it is in ipRGCs. Amacrine-to-bipolar cell feedback seems to contribute surprisingly little to this filtering, implicating mostly postsynaptic mechanisms. Most ipRGCs sample from all bipolar terminals costratifying with their dendrites, but M1 cells avoid all OFF bipolar input and accept only ectopic ribbon synapses from ON cone bipolar axonal shafts. These are remarkable monad synapses, equipped with as many as a dozen ribbons and only one postsynaptic process.