Enteric glial cell heterogeneity regulates intestinal stem cell niches.

The high turnover and regenerative capacity of the adult intestine relies on resident stem cells located at the bottom of the crypt. The enteric nervous system consists of an abundant network of enteric glial cells (EGCs) and neurons. Despite the close proximity of EGCs to stem cells, their in vivo role as a stem cell niche is still unclear. By analyzing the mouse and human intestinal mucosa transcriptomes at the single-cell level, we defined the regulation of EGC heterogeneity in homeostasis and chronic inflammatory bowel disease. Ablation of EGC subpopulations revealed that the repair potential of intestinal stem cells (ISCs) is regulated by a specific subset of glial fibrillary acidic protein (GFAP)+ EGCs. Mechanistically, injury induces expansion of GFAP+ EGCs, which express several WNT ligands to promote LGR5+ ISC self-renewal. Our work reveals the dynamically regulated heterogeneity of EGCs as a key part of the intestinal stem cell niche in regeneration and disease.

Starvation-Induced Depotentiation of Bitter Taste in Drosophila.

Nutrient deprivation can lead to dramatic changes in feeding behavior, including acceptance of foods that are normally rejected. In flies, this behavioral shift depends in part on reciprocal sensitization and desensitization of sweet and bitter taste, respectively. However, the mechanisms for bitter taste modulation remain unclear. Here, we identify a set of octopaminergic/tyraminergic neurons, named OA-VLs, that directly modulate bitter sensory neuron output in response to starvation. OA-VLs are in close proximity to bitter sensory neuron axon terminals and show reduced tonic firing following starvation. We find that octopamine and tyramine potentiate bitter sensory neuron responses, suggesting that starvation-induced reduction in OA-VL activity depotentiates bitter taste. Consistent with this model, artificial silencing of OA-VL activity induces a starvation-like reduction in bitter sensory neuron output. These results demonstrate that OA-VLs mediate a critical step in starvation-dependent bitter taste modulation, allowing flies to dynamically balance the risks associated with bitter food consumption against the threat of severe starvation.

Presynaptic gain control drives sweet and bitter taste integration in Drosophila.

The sense of taste is critical in determining the nutritional suitability of foods. Sweet and bitter are primary taste modalities in mammals, and their behavioral relevance is similar in flies. Sweet taste drives the appetitive response to energy sources, whereas bitter taste drives avoidance of potential toxins and also suppresses the sweet response [1, 2]. Despite their importance to survival, little is known about the neural circuit mechanisms underlying integration of sweet and bitter taste. Here, we describe a presynaptic gain control mechanism in Drosophila that differentially affects sweet and bitter taste channels and mediates integration of these opposing stimuli. Gain control is known to play an important role in fly olfaction, where GABAB receptor (GABABR) mediates intra- and interglomerular presynaptic inhibition of sensory neuron output [3-5]. In the taste system, we find that gustatory receptor neurons (GRNs) responding to sweet compounds express GABABR, whereas those that respond to bitter do not. GABABR mediates presynaptic inhibition of calcium responses in sweet GRNs, and both sweet and bitter stimuli evoke GABAergic neuron activity in the vicinity of GRN axon terminals. Pharmacological blockade and genetic reduction of GABABR both lead to increased sugar responses and decreased suppression of the sweet response by bitter compounds. We propose a model in which GABA acts via GABABR to expand the dynamic range of sweet GRNs through presynaptic gain control and suppress the output of sweet GRNs in the presence of opposing bitter stimuli.

Rehabilitating a dialysis patient.

End-stage renal disease (ESRD) patients undergoing dialysis face much stress and have to make adjustments in their lives. To optimize health and improve quality of life, rehabilitation of renal patients is a necessity. Renal rehabilitation includes physical, social, psychological, and vocational elements. We established a renal rehabilitation program--including predialysis education, incenter training, and community rehabilitation--in our regional dialysis unit. The program is organized by a multidisciplinary team of health professionals with the help of a renal-patient support group. A patient who joined the rehabilitation program showed significant lifestyle change.