Biology subjects

Ehmann, N.

Publications and source records attributed to Ehmann, N..

5 recordsLinked to original sources

bioRxiv2025

Stabilized ion selectivity corrects activation drift in kalium channelrhodopsins

Effective optogenetic inhibition of neuronal activity requires tools that can reliably silence neurons across diverse conditions and cell types. Potassium-selective channelrhodopsins (KCRs) have emerged as promising alternatives to chloride-conducting channels for optogenetic inhibition of cellular excitability, but they exhibit dynamic ion selectivity shift under prolonged or intense illumination, causing activation. This inhibition to activation transition limits their utility for silencing circuits. Through behavioral and electrophysiological analyses in Drosophila, and C. elegans, we found that the C29D variant of KCR1 maintains the most stable potassium selectivity among tested variants. While other KCR variants showed excitation defects, KCR1-C29D consistently provided robust in vivo inhibition across cell types, illumination conditions, and species. Electrophysiological recordings revealed that while most KCRs show declining PK/PNa ratios during illumination, KCR1-C29D maintains stable ion selectivity, consistent with its robust silencing capability. This work resolves a key limitation of KCR optogenetics and shows that KCR1-C29D is a superior tool for reliable inhibition. Our findings offer valuable mechanistic and practical insights for the design of next generation optogenetic inhibitors.

neuroscience↗

bioRxiv2023

Rab3 mediates cyclic AMP-dependent presynaptic plasticity and olfactory learning

Presynaptic forms of plasticity occur throughout the nervous system and play an important role in learning and memory but the underlying molecular mechanisms are insufficiently understood. Here we show that the small GTPase Rab3 is a key mediator of cyclic AMP (cAMP)-induced presynaptic plasticity in Drosophila. Pharmacological and optogenetic cAMP production triggered concentration-dependent alterations of synaptic transmission, including potentiation and depression of evoked neurotransmitter release, as well as strongly facilitated spontaneous release. These changes correlated with a nanoscopic rearrangement of the active zone protein Unc13A and required Rab3. To link these results to animal behaviour, we turned to the established role of cAMP signalling in memory formation and demonstrate that Rab3 is necessary for olfactory learning. As Rab3 is dispensable for basal synaptic transmission, these findings highlight a molecular pathway specifically dedicated to tuning neuronal communication and adaptive behaviour.

neuroscience↗

bioRxiv2021

Molecular Mechanisms of Neurotransmitter Release Control Distinct Features of Sensory Coding Reliability

To survive, animals must recognize reoccurring stimuli. A key requirement for repeated identification of stimuli is reliable representation by the neural code on each encounter. Synaptic transmission underlies neural codes propagation between brain regions. A hallmark of chemical synapses is their plasticity, which enables signal transfer to be modified in an activity-dependent manner. Despite many decades of intense research on synapses, it remains unclear how the plastic features of synaptic transmission can maintain reliable neural coding. By studying the olfactory system of Drosophila melanogaster, we aimed to obtain a deeper mechanistic understanding of how synaptic function shapes neural coding reliability in the live, behaving animal. We show that the properties of the active zone (AZ), the presynaptic site of neurotransmitter release, are critical for generating a reliable neural code. Reducing neurotransmitter release probability specifically at AZs of olfactory sensory neurons disrupted both neural coding and behavioral reliability. Strikingly, these defects were rescued within a day by target-specific synaptic plasticity, whereby a homeostatic increase in the number of AZs compensated the drop in release probability. These findings demonstrate an important role for synaptic plasticity in maintaining neural coding reliability and are of pathophysiological interest by uncovering an elegant mechanism through which the neural circuitry can counterbalance perturbations.

neuroscience↗

bioRxiv2020

Antinociceptive modulation by the adhesion-GPCR CIRL promotes mechanosensory signal discrimination

Adhesion-type G protein-coupled receptors (aGPCRs) participate in a vast range of physiological processes. Correspondingly, these receptors are associated with diverse human diseases, such as developmental disorders, defects of the nervous system, allergies and cancer. Several aGPCRs have recently been linked to mechanosensitive functions suggesting that processing of mechanical stimuli may be a common feature of this receptor family. CIRL (ADGRL/Latrophilin, LPHN), one of the oldest members of the aGPCR family, sensitizes sensory responses of larval Drosophila to gentle touch and sound by amplifying mechanosensory signal transduction in low-threshold mechanoreceptors (Scholz et al., 2015; 2017). In the present study, we show that Cirl is also expressed in high-threshold mechanical nociceptors where it adjusts nocifensive behaviour under physiological and pathophysiological conditions. Optogenetic in vivo experiments indicate that CIRL quenches cAMP levels in both mechanosensory submodalities. However, contrasting its effect in touch sensitive neurons, CIRL dampens the response of nociceptors to mechanical stimulation. Consistent with this finding, rat nociceptors display a drop in Cirl1 expression during allodynia. Taken together, these results demonstrate that CIRL exerts opposing modulatory functions in low-threshold mechanosensors and high-threshold nociceptors. This intriguing bipolar action likely facilitates the separation of mechanosensory signals carrying different physiological information.

physiology↗

bioRxiv2018

Complexin cooperates with Bruchpilot to tether synaptic vesicles to the active zone cytomatrix

Information processing by the nervous system depends on the release of neurotransmitter from synaptic vesicles (SVs) at the presynaptic active zone. Molecular components of the cytomatrix at the active zone (CAZ) regulate the final stages of the SV cycle preceding exocytosis and thereby shape the efficacy and plasticity of synaptic transmission. Part of this regulation is reflected by a physical association of SVs with filamentous CAZ structures. However, our understanding of the protein interactions underlying SV tethering by the CAZ is far from complete. The very C-terminal region of Bruchpilot (Brp), a key component of the Drosophila CAZ, participates in SV tethering. Yet so far, no vesicular or cytoplasmic molecules have been reported to engage in an interaction with Brps C-terminus. Here, we carried out an in vivo screen for molecules that link the Brp C-terminus to SVs. This strategy identified the conserved SNARE (soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein receptor) regulator Complexin (Cpx) as a vesicular interaction partner of Brp. We show that Brp and Cpx interact genetically and functionally. Interfering with Cpx targeting to SVs mirrored distinctive features of a C-terminal Brp truncation: impaired SV recruitment to the CAZ and enhanced short-term synaptic depression. Extending the study beyond Drosophila synapses, we interrogated active zones of mouse rod bipolar cells. Here, too, we collected evidence for an evolutionarily conserved role of Cpx upstream of SNARE complex assembly where it participates in SV tethering to the CAZ.

neuroscience↗