Biology subjects

Henning, M.

Publications and source records attributed to Henning, M..

3 recordsLinked to original sources

bioRxiv2025

Time-resolved structures of β2-adrenergic receptor modulation by a photoswitchable beta-blocker

G protein-coupled receptors (GPCRs) regulate essential physiological responses and are important drug targets, yet their ligand-induced conformational dynamics remain poorly understood. The {beta}2-adrenergic receptor ({beta}2AR) is a prominent member of the GPCR family. It regulates bronchial and vascular function and is a significant drug target, particularly in respiratory and smooth muscle-related disorders. We employed time-resolved crystallography at X-ray free-electron lasers (XFELs) to capture the conformational dynamics of {beta}2AR bound to photoazolol-1, a beta-blocker derivative developed for photopharmacological applications. Structural snapshots of the receptor bound to trans-photoazolol-1 (pre-photoconversion), a strained intermediate, and the fully photoisomerized cis-photoazolol-1 reveal an intricate interplay between ligand chemistry and receptor plasticity. Isomerization of the azobenzene moiety induces distinct conformational changes within the orthosteric pocket, altering interactions with the extracellular loop 2 and transmembrane helices 5 and 6. Supported by functional assays, these structural shifts suggest that photoazolol-1 transitions from an inverse agonist to a neutral antagonist upon photoactivation. Our findings uncover a mechanism of GPCR modulation reminiscent of rhodopsin activation and offer a framework for designing ligands that harness light-driven transitions to achieve spatiotemporal control of receptor function.

biochemistry↗

bioRxiv2025

Inhibitory columnar feedback neurons are required for motion processing in Drosophila

Visual motion information is essential to guiding the movements of many animals. The establishment of direction-selective signals, a hallmark of motion detection, is considered a core neural computation and has been characterized extensively in primates, mice and fruit flies. In flies, the circuits that produce direction-selective signals rely on feedforward visual pathways that connect peripheral visual inputs to the dendrites of the ON and OFF-direction selective cells. Here we describe a novel role for feedback inhibition in motion computation. Two GABAergic neurons, C2 and C3, connect to neurons upstream of the direction-selective T4 and T5 cells and blocking C2 and C3 affects direction selectivity in T4/T5. In the ON pathway, this is likely achieved by C2-mediated suppression of responses in the major T4 input neuron Mi1. Together, C2 and C3 suppress responses to non-preferred stimuli in both T4 and T5. At the behavioral level, feedback inhibition temporally sharpens responses to ON-moving stimuli, enhancing the flys ability to discriminate visual stimuli that occur in quick succession. GABAergic inhibitory feedback neurons thus constitute an essential component within the circuitry that computes visual motion.

neuroscience↗

bioRxiv2021

An optimal population code for global motion estimation in local direction-selective cells

Nervous systems allocate computational resources to match stimulus statistics. However, the physical information that needs to be processed depends on the animals own behavior. For example, visual motion patterns induced by self-motion provide essential information for navigation. How behavioral constraints affect neural processing is not known. Here we show that, at the population level, local direction-selective T4/T5 neurons in Drosophila represent optic flow fields generated by self-motion, reminiscent to a population code in retinal ganglion cells in vertebrates. Whereas in vertebrates four different cell types encode different optic flow fields, the four uniformly tuned T4/T5 subtypes described previously represent a local snapshot. As a population, six T4/T5 subtypes encode different axes of self-motion. This representation might serve to efficiently encode more complex flow fields generated during flight. Thus, a population code for optic flow appears to be a general coding principle of visual systems, but matching the animals individual ethological constraints.

neuroscience↗