CIG – NEWS

Cold Spring Harb Protoc. 2022 Nov 29. doi: 10.1101/pdb.prot108063. Online ahead of print.

Recording from Fly Olfactory Sensilla

Richard Benton ¹, Anupama Dahanukar ²

Abstract

Olfactory systems detect and discriminate an enormous diversity of volatile environmental stimuli and provide important paradigms to investigate how sensory cues are represented in the brain. Key stimulus-coding events occur in peripheral olfactory sensory neurons, which typically express a single olfactory receptor-from a large repertoire encoded in the genome-with a defined ligand-response profile. These receptors convert odor ligand recognition into spatial and temporal patterns of neural activity that are transmitted to, and interpreted in, central brain regions. Drosophila provides an attractive model to study olfactory coding because it possesses a relatively simple peripheral olfactory system that displays many organizational parallels to those of vertebrates. Moreover, nearly all olfactory sensory neurons have been molecularly characterized and are accessible for physiological analysis, as they are exposed on the surface of sensory organs (antennae and maxillary palps) housed in specialized hairs called sensilla. This protocol describes how to perform recordings of odor-evoked activity from Drosophila olfactory sensilla, covering the basics of sample preparation, setting up the electrophysiology rig, assembling an odor stimulus-delivery device, and data analysis. The methodology can be used to characterize the ligand-recognition properties of most olfactory sensory neurons and the role of olfactory receptors (and other molecular components) in signal transduction.

• PMID: 36446530
• DOI: 10.1101/pdb.prot108063

Cold Spring Harb Protoc. 2022 Nov 29. doi: 10.1101/pdb.prot108064. Online ahead of print.

Recording from Fly Taste Sensilla

Anupama Dahanukar ¹, Richard Benton ²Affiliations expand

Abstract

Gustatory systems sense chemicals upon contact and provide a model to investigate how these stimuli are encoded to inform various behavioral decisions including choice of foods, egg-laying sites, and mating partners. Multiple organs in the body house peripheral gustatory sensory neurons, the axons of which project to discrete regions in the subesophageal zone and ventral ganglion, representing both the location and quality of the taste stimulus. Taste neurons are broadly divided into subpopulations associated with either positive or negative behavioral valence, each expressing combinations of taste receptors-in some cases, more than 30 receptors-encoded by one or more chemosensory gene families that together determine their chemical response properties. Drosophila provides a powerful model to study gustatory coding because a majority of the taste sensory units (sensilla) are present in external taste organs (labellum and legs) and are accessible for electrophysiological analysis of tastant-evoked responses. Moreover, a large body of work on the basic characteristics of individual taste neurons housed in a sensillum, as well as on functional surveys of entire taste organs, provides a foundation for investigating further questions about taste coding, adaptability, and evolution. This protocol describes how to perform recordings of stimulus-evoked activity from Drosophila taste sensilla covering the basics of setting up the electrophysiology rig and stimulus-delivery device, sample preparation, and performing and analyzing the recordings.

• PMID: 36446534
• DOI: 10.1101/pdb.prot108064

Pharmacol Res. 2022 Nov 23;187:106578. doi: 10.1016/j.phrs.2022.106578. Online ahead of print.

A positive feedback loop between AMPK and GDF15 promotes metformin antidiabetic effects

David Aguilar-Recarte ¹, Emma Barroso ¹, Meijian Zhang ¹, Patricia Rada ², Javier Pizarro-Delgado ¹, Lucía Peña ¹, Xavier Palomer ¹, Ángela M Valverde ², Walter Wahli ³, Manuel Vázquez-Carrera ⁴

Abstract

Background and aims: Metformin, the most prescribed drug for the treatment of type 2 diabetes mellitus, has been recently reported to promote weight loss by upregulating the anorectic cytokine growth differentiation factor 15 (GDF15). Since the antidiabetic effects of metformin are mostly mediated by the activation of AMPK, a key metabolic sensor in energy homeostasis, we examined whether the activation of this kinase by metformin was dependent on GDF15.

Methods: Cultured hepatocytes and myotubes, and wild-type and Gdf15^-/- mice were utilized in a series of studies to investigate the involvement of GDF15 in the activation of AMPK by metformin.

Results: A low dose of metformin increased GDF15 levels without significantly reducing body weight or food intake, but it ameliorated glucose intolerance and activated AMPK in the liver and skeletal muscle of wild-type mice but not Gdf15^-/- mice fed a high-fat diet. Cultured hepatocytes and myotubes treated with metformin showed AMPK-mediated increases in GDF15 levels independently of its central receptor GFRAL, while Gdf15 knockdown blunted the effect of metformin on AMPK activation, suggesting that AMPK is required for the metformin-mediated increase in GDF15, which in turn is needed to sustain the full activation of this kinase independently of the CNS.

Conclusion: Overall, these findings uncover a novel mechanism through which GDF15 upregulation by metformin is involved in achieving and sustaining full AMPK activation by this drug independently of the CNS.

Keywords: AMPK; GDF15; Glucose tolerance; Metformin.

• PMID: 36435271
• DOI: 10.1016/j.phrs.2022.106578

Eur J Hum Genet. 2022 Dec 1. doi: 10.1038/s41431-022-01241-4. Online ahead of print.

Reply to Letter by Tellier et al., ‘Scientific refutation of ESHG statement on embryo selection’

Francesca Forzano ¹, Olga Antonova ², Angus Clarke ³, Guido de Wert ⁴, Sabine Hentze ⁵, Yalda Jamshidi ⁶, Yves Moreau ⁷, Markus Perola ⁸, Inga Prokopenko ^9 10 11, Andrew Read ¹², Alexandre Reymond ¹³, Vigdis Stefansdottir ¹⁴, Carla van El ¹⁵, Maurizio Genuardi ^16 17, Executive Committee of the European Society of Human Genetics; Public and Professional Policy Committee of the European Society of Human Genetics

No abstract available

• PMID: 36450798
• DOI: 10.1038/s41431-022-01241-4