Biology subjects

Siegenthaler, D.

Publications and source records attributed to Siegenthaler, D..

3 recordsLinked to original sources

bioRxiv2024

Visual objects refine head direction coding

Animals use visual objects to guide navigation-related behaviors, from hunting prey, to escaping predators, to exploring the world. However, little is known about where visual objects are encoded in the mouse brain or how they impact processing in the spatial navigation system. Using functional ultrasound imaging in mice, we conducted a brain-wide screen and identified brain areas that were preferentially activated by images of objects compared to scrambled versions of the same images. While visual cortical areas did not show a significant preference, regions associated with spatial navigation were preferentially activated by visual objects. Electrophysiological recordings in postsubiculum, the primary cortical area of the head direction (HD) system, further confirmed a preference for visual objects, which was present in both HD cells and fast-spiking interneurons. Finally, we found that visual objects dynamically modulated HD cells, selectively increasing firing rates of HD cells aligned with a visual landmarks direction, while decreasing activity in HD cells coding for other directions. These results reveal that visual objects refine population-level coding of head direction.

neuroscience↗

bioRxiv2023

Efficient and sustained optogenetic control of nervous and cardiac systems

Optogenetic control is used to manipulate the activity of specific cell types in vivo for a variety of biological and clinical applications. Here we report ChReef, an improved variant of the channelrhodopsin ChRmine. ChReef offers minimal photocurrent desensitization, a unitary conductance of 80 fS and closing kinetics of 30 ms, which together enable reliable optogenetic control of cells at low light levels with good temporal fidelity and sustained stimulation. We demonstrate efficient and reliable red-light pacing and depolarization-block of ChReef-expressing cardiomyocyte clusters. We used AAV-based gene transfer to express ChReef in retinal ganglion cells, where it restores visual function in blind mice with light sources as weak as an iPad screen. Toward optogenetic hearing restoration, ChReef enables stimulation of the auditory pathway in rodents and non-human primates with nano-Joule threshold, enabling efficient and frequency-specific stimulation by LED-based optical cochlear implants.

biophysics↗

bioRxiv2023

The COMBO window: A chronic cranial implant for multiscale circuit interrogation in mice

Neuroscientists studying the neural correlates of mouse behavior often lack access to the brain-wide activity patterns elicited during a specific task of interest. Fortunately, large-scale imaging is becoming increasingly accessible thanks to modalities such as Ca2+ imaging and functional ultrasound (fUS). However, these and other techniques often involve challenging cranial window procedures, and are difficult to combine with other neuroscience tools. We address this need with an open-source 3D-printable cranial implant - the COMBO (ChrOnic Multimodal imaging and Behavioral Observation) window. The COMBO window enables chronic imaging of large portions of the brain in head-fixed mice while preserving orofacial movements. We validate the COMBO window stability using both brain-wide fUS and multi-site two-photon imaging. Moreover, we demonstrate how the COMBO window facilitates the combination of optogenetics, fUS and electrophysiology in the same animals to study the effects of circuit perturbations at both the brain-wide and single-neuron level. Overall, the COMBO window provides a versatile solution for performing multimodal brain recordings in head-fixed mice.

neuroscience↗