Each taste modality is generally encoded by a single, molecularly defined, population of sensory cells. However, salt stimulates multiple taste pathways in mammals and insects, suggesting a more complex code for salt taste. Here, we examine salt coding in Drosophila. After creating a comprehensive molecular map comprised of five discrete sensory neuron classes across the fly labellum, we find that four are activated by salt: two exhibiting characteristics of ‘low salt’ cells, and two ‘high salt’ classes. Behaviorally, low salt attraction depends primarily on ‘sweet’ neurons, with additional input from neurons expressing the ionotropic receptor IR94e. High salt avoidance is mediated by ‘bitter’ neurons and a population of glutamatergic neurons expressing Ppk23. Interestingly, the impact of these glutamatergic neurons depends on prior salt consumption. These results support a complex model for salt coding in flies that combinatorially integrates inputs from across cell types to afford robust and flexible salt behaviors.

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Stanley and colleagues explore whether changes in insulin levels and insulin signaling are a cause or consequence of AD.

Alzheimer disease (AD) is the most common cause of dementia and is characterized by the aggregation and accumulation of two proteins in the brain, amyloid-β (Aβ) and tau. Aβ and tau begin to buildup 15-20 years before the clinical onset of AD dementia. Increasing evidence suggests that preventing or decreasing the amount of aggregated forms of both Aβ and tau in the brain can serve as potential disease-modifying treatments for AD.

Hyperinsulinemia is a risk factor for late-onset Alzheimer's disease (AD).In vitro experiments describe potential connections between insulin, insulin signaling, and amyloid-␤ (A␤), but in vivo experiments are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving APP swe /PS1 dE9 transgenic mice. Both a postprandial and supraphysiological insulin clamp significantly increased interstitial fluid (ISF) and plasma A␤ compared with controls. We could detect no increase in brain, ISF, or CSF insulin or brain insulin signaling in response to peripheral hyperinsulinemia, despite detecting increased signaling in the muscle. Next, we delivered insulin directly into the hippocampus of young APP/PS1 mice via reverse microdialysis. Brain tissue insulin and insulin signaling was dose-dependently increased, but ISF A␤ was unchanged by central insulin administration. Finally, to determine whether peripheral and central high insulin has differential effects in the presence of significant amyloid pathology, we repeated these experiments in older APP/PS1 mice with significant amyloid plaque burden. Postprandial insulin clamps increased ISF and plasma A␤, whereas direct delivery of insulin to the hippocampus significantly increased tissue insulin and insulin signaling, with no effect on A␤ in old mice. These results suggest that the brain is still responsive to insulin in the presence of amyloid pathology but increased insulin signaling does not acutely modulate A␤ in vivo before or after the onset of amyloid pathology. Peripheral hyperinsulinemia modestly increases ISF and plasma A␤ in young and old mice, independent of neuronal insulin signaling.