Biology subjects

Semmelhack, J.

Publications and source records attributed to Semmelhack, J..

5 recordsLinked to original sources

bioRxiv2025

Toward Crosstalk-free All-optical Interrogation of Neural Circuits

All-optical interrogation, based on high-resolution two-photon stimulation and imaging, has emerged as a potentially transformative approach in neuroscience, allowing for the simultaneous precise manipulation and monitoring of neuronal activity across various model organisms. However, the unintended excitation of light-gated ion channels such as channelrhodopsin (ChR) during two-photon calcium imaging with genetically encoded calcium indicators (GECIs) introduces artifactual neuronal perturbation and contaminates neural activity measurements. In this study, we propose an active pixel power control (APPC) approach, which dynamically adjusts the imaging laser power at each scanning pixel, to address the challenge. We aim to achieve simultaneous two-photon optogenetic manipulation and calcium imaging with a single femtosecond laser, while minimizing the crosstalk between manipulation and imaging. To study this technologys capabilities, we applied it to the larval zebrafish brain in vivo. Our results demonstrate that the APPC approach preserves GECI signal quality while suppressing optogenetic artifacts significantly. This enhances the accuracy of neural circuit dissection and advances the precision of all-optical interrogation, offering a robust framework for probing neural circuit dynamics and causality in vivo with high fidelity, potentially across various model organisms. Importantly, this technology can be seamlessly integrated with commonly used two-photon microscope systems in laboratories worldwide.

neuroscience↗

bioRxiv2025

Neuropeptide signalling and perineurial barrier generate a persistent stress-induced internal state in Drosophila

Although fear conditioning has elucidated cue-evoked acute fear responses, the mechanisms by which stress experiences induce generalized internal states linked to anxiety are poorly understood. Here, we report that robust stress induces a persistent behavioral change characterized by avoidance of a confined space, claustrophobia-like behavior in Drosophila. Unlike aversive memory formation, the development of claustrophobia-like behavior does not require dopamine receptors. Our neuronal screening determined that neuropeptide signalling via Allatostatin-A inactivates the downstream neurons via its receptor AstA-R1, causally inducing claustrophobia-like behavior. Moreover, gene expression profiling of individual fly heads revealed that immune response activation in perineurial barrier is involved in claustrophobia-like behavior. Our data demonstrate that stress-induced persistent behavioral change would not be related to a canonical mechanism of aversive memory formation, rather involves neuropeptidergic signalling and perineurial barrier, providing the mechanism determining internal states which persistently change behavioral modes.

neuroscience↗

bioRxiv2024

Parental thermal conditions affect the brain activity response to alarm cue in larval zebrafish

With temperature being a crucial factor affecting the physiology of ectothermic animals, global warming will likely impact neural mechanisms aquatic organisms use to perceive their environment over generations. However, exposure to elevated temperature during specific life stages and across generations may confer fish resilience through phenotypic plasticity. In this study, we investigate the effects of developmental and parental temperature on brain activity response to an olfactory cue in the larval zebrafish, Danio rerio. We exposed parents during reproduction and their offspring during development to control (28{degrees}C) or elevated temperature (30{degrees}C) and observed the response of the larval telencephalon to an alarm cue using live calcium imaging. Parental exposure to elevated temperature decreased the time till maximum brain activity response regardless of the offsprings developmental temperature, revealing that parental thermal conditions can affect the excitability of the offsprings neural circuitry. Furthermore, brain activity duration was affected by the interaction between parental and offspring thermal conditions, tending to last longer when either parents or offspring were exposed to elevated temperature, yet more similar to control when elevated temperature was experienced by both parents and offspring. This could represent an anticipatory parental effect influencing the offsprings brain response to match the parental environment, or an early developmental effect occurring within a susceptible short time window post-fertilization. Overall, our results suggest that future predicted warming can alter processes involved in brain transmission and show that parental conditions could aid in the preparation of their offspring to respond to olfactory stimuli in a changing environment.

physiology↗

bioRxiv2023

Warming affects routine swimming activity and novel odour molecular response in larval zebrafish

Temperature is a primary factor affecting the survival, development, and physiology of aquatic ectothermic animals and global warming of water bodies may therefore impact several biological levels of aquatic life. Understanding the effects of near-future predicted temperature changes on the behaviour and the underlying molecular mechanisms of aquatic animals is of particular importance, since behaviour mediates key interactions and, in turn, population dynamics. In this study, we investigate the effects of elevated developmental temperature on locomotor behaviour and olfactory learning in the zebrafish, Danio rerio. We exposed zebrafish from cleavage embryonic stage to either current day control (28{degrees}C) or predicted future elevated temperature (30{degrees}C) for seven days. Overall, warming reduced the total routine swimming distance and caused the upregulation of a small number of genes involved in metabolism and neuron development, suggesting accelerated development at elevated temperature. When fish were exposed to two different olfactory cues, namely catfish cue, a non-alarming but novel odour, and injured conspecifics alarm cue expected to cause a fear reaction, warming differently affected larvae response to the two cues. In particular, a large transcriptional reprogramming was observed at elevated temperature in response to novel odour exposure, with upregulation of cell signalling, neuron development and neuron functioning genes. As this response was coupled with downregulation of genes involved in protein translation and ATP metabolism, it indicates that novel odour recognition in future-predicted thermal conditions will require energetic trade-offs between expensive baseline processes and responsive functions. To also evaluate their learning abilities at both temperatures, 7 days post fertilization (dpf) zebrafish were conditioned with a mixture of injured conspecifics alarm cue and non-alarming catfish cue. Regardless of temperature, no behavioural (freezing) nor gene expression changes were detected, reinforcing our previous findings that warming mainly affects zebrafish molecular response to novel odours. Overall, our results show that future thermal conditions will likely impact developing stages, causing energy trade-offs following olfactory detection of novel substances in the environment.

molecular biology↗

bioRxiv2020

What the Zebrafish's Eye Tells the Zebrafish's Brain: Retinal Ganglion Cells for Prey Capture and Colour Vision

In vertebrate vision, the tetrachromatic larval zebrafish permits non-invasive monitoring and manipulating of neural activity across the nervous system in vivo during ongoing behaviour. However, despite a perhaps unparalleled understanding of links between zebrafish brain circuits and visual behaviours, comparatively little is known about what their eyes send to the brain in the first place via retinal ganglion cells (RGCs). Major gaps in knowledge include any information on spectral coding, and information on potentially critical variations in RGC properties across the retinal surface to acknowledge asymmetries in the statistics of natural visual space and behavioural demands. Here, we use in vivo two photon (2P) imaging during hyperspectral visual stimulation as well as photolabeling of RGCs to provide the first eye-wide functional and anatomical census of RGCs in larval zebrafish. We find that RGCs functional and structural properties differ across the eye and include a notable population of UV-responsive On-sustained RGCs that are only found in the acute zone, likely to support visual prey capture of UV-bright zooplankton. Next, approximately half of RGCs display diverse forms of colour opponency - long in excess of what would be required to satisfy traditional models of colour vision. However, most information on spectral contrast was intermixed with temporal information. To consolidate this series of unexpected findings, we propose that zebrafish may use a novel "dual-achromatic" strategy segregated by a spectrally intermediate background subtraction system. Specifically, our data is consistent with a model where traditional achromatic image-forming vision is mainly driven by long-wavelength sensitive circuits, while in parallel UV-sensitive circuits serve a second achromatic system of foreground-vision that serves prey capture and, potentially, predator evasion.

neuroscience↗