Biology subjects

Schwarz, M. K.

Publications and source records attributed to Schwarz, M. K..

8 recordsLinked to original sources

bioRxiv2026

Millisecond-scale detection of mouse ultrasonic vocalizations enables closed-loop experiments

Mouse ultrasonic vocalizations (USVs) provide a rapidly evolving readout of social interaction but are typically analysed only after acquisition. Here we introduce DeepFisFis, a waveform-based neural network that detects USVs while they are being produced. DeepFisFis classifies consecutive 5 ms audio segments directly from the waveform with high accuracy, processing each segment in approximately 2.5 ms and therefore faster than the incoming audio stream. This enables ongoing vocalizations to guide experimental interventions in real time. In a deployed closed-loop system, detections triggered an external stimulus, demonstrating online control of ongoing vocal behaviour. DeepFisFis also enables event-triggered data acquisition: gating storage around detected calls preserved more than 99% of vocalization time while retaining only approximately 22% of the continuous recording. DeepFisFis thus transforms USVs from a retrospective behavioural readout into a real-time experimental signal for selective acquisition and closed-loop causal interrogation of vocal communication and its underlying neural circuits.

neuroscience↗

bioRxiv2026

In vitro programming and pseudounipolarization of human iPSC-derived sensory neurons

Ectopic expression of NGN1, BRN3A and ISLET1 (NBI) from a safe harbor locus in induced pluripotent stem cells (iPSCs) yielded robust differentiation into functional sensory neurons (iNBI-SNs) within seven days. Single nucleus transcriptomics identified peripheral sensory neuron profiles of nociceptors and mechanoreceptors. Electrophysiological studies showed that more than 98 % of iNBI-SNs display TTX-resistant sodium currents and that they establish functional connections to excitatory CNS neurons. iNBI-SNs derived from patients with inherited erythromelalgia, a pain disorder associated with gain-of-function mutations in the Nav1.7 sodium channel showed pathologically increased firing rates which could be partially rescued with a Nav1.7 inhibitor. Notably, iNBI-SNs acquire a characteristic pseudounipolar morphology upon co-culture with embryonic rodent DRG cells. Taken together, NBI-based forward programming of iPSCs represents a robust approach for the generation of human sensory neurons suitable for developmental, disease- and therapy-related studies.

neuroscience↗

bioRxiv2025

Nanoscale dendritic shaft constrictions shape synaptic integration in fine caliber principal neuron dendrites

Traditionally, theoretical studies typically described dendritic morphology as optimized for efficient synaptic voltage transfer from spines to the soma, implemented as a tubular design respecting Ralls 3/2 rule for impedance matching at branch points. Here, we reveal that this view is an oversimplification. Using three high-resolution imaging techniques, we demonstrate that dendrites in cortical and hippocampal neurons contain nanoscale constrictions, comparable in diameter to spine necks. We provide theoretical and experimental evidence that these constrictions partition the dendrite into distinct electrical compartments, significantly shaping dendritic integration of synaptic potentials.

neuroscience↗

bioRxiv2022

A-SOiD, an active learning platform for expert-guided, data efficient discovery of behavior

To identify and extract naturalistic behavior, two schools of methods have become popular: supervised and unsupervised. Each approach carries its own strengths and weaknesses, which the user must weigh in on their decision. Here, a new active learning platform, A-SOiD, blends these strengths and, in doing so, overcomes several of their inherent drawbacks. A-SOiD iteratively learns user-defined groups and can considerably reduce the necessary training data while attaining expansive classification through directed unsupervised classification. In socially-interacting mice, A-SOiD outperformed other methods and required 85% less training data than was available. Additionally, it isolated two additional ethologically-distinct mouse interactions via unsupervised classification. Similar performance and efficiency were observed using non-human primate 3D pose data. In both cases, the transparency in A-SOiDs cluster definitions revealed the defining features of the supervised classification through a game-theoretic approach. Lastly, we show the potential of A-SOiD to segment a large and rich variety of human social and single-person behaviors with 3D position keypoints. To facilitate use, A-SOiD comes as an intuitive, open-source interface for efficient segmentation of user-defined behaviors and discovered sub-actions.

animal behavior and cognition↗

bioRxiv2021

Imaging Three-Dimensional Brain Organoid Architecture from Meso- to Nanoscale across Development

Organoids are human stem cell-derived three-dimensional cultures offering a new avenue to model human development and disease. Brain organoids allow studying various aspects of human brain development in the finest details in vitro in a tissue-like context. However, spatial relationships of subcellular structures such as synaptic contacts between distant neurons are hardly accessible by conventional light microscopy. This limitation can be overcome by systems that quickly image the entire organoid in three dimensions and in super-resolution. To that end we have developed a setup combining tissue expansion and light sheet fluorescence microscopy for imaging and quantifying diverse spatial parameters during organoid development. This technique enables zooming from a mesoscopic perspective into super-resolution within a single imaging session, thus revealing cellular and subcellular structural details in three spatial dimensions, including unequivocal delineation of mitotic cleavage planes as well as the alignment of pre- and postsynaptic proteins. We expect light sheet fluorescence expansion microscopy (LSFEM) to facilitate qualitative and quantitative assessment of organoids in developmental and disease-related studies. Summary statementThe combination of light sheet fluorescence and expansion microscopy enables imaging of mature human brain organoids in toto and down to synaptic resolution

neuroscience↗

bioRxiv2020

The diagonal band of broca continually regulates olfactory-mediated behaviors by modulating odor-evoked responses within the olfactory bulb

Sensory perception is modulated in a top-down fashion by higher brain regions to regulate the strength of its own input resulting in the adaptation of behavioral responses. In olfactory perception, the horizontal diagonal band of broca (HDB), embedded in the basal forebrain modulates olfactory information processing by recruiting olfactory bulb (OB) interneurons to shape excitatory OB output. Currently, little is known about how specific HDB to OB top-down signaling affects complex olfactory-mediated behaviors. Here we show that the olfactory bulb is strongly and differentially innervated by HDB projections. HDB-silencing via tetanus toxin light chain led to reduced odor-evoked Ca2+-responses in glomeruli of the OB, underscoring HDBs role in odor response modulation. Furthermore, selective, light-mediated silencing of HDB to OB afferents completely prevented olfactory-mediated habituation and discrimination behaviors. Notably, also social habituation and discrimination behaviors were affected. Mono-transsynaptic tracing studies indicated a robust HDB innervation from the paraventricular nucleus (PVN). Here we provide evidence for a novel tri-synaptic PVN-HDB-OB axis responsible for modulating these types of behavior. Thus, HDB to OB projections constitute a central top-down pathway for olfactory-mediated habituation and discrimination behaviors.

neuroscience↗

bioRxiv2019

DeepLabStream: Closing the loop using deep learning-based markerless, real-time posture detec-tion

In general, animal behavior can be described as the neuronal-driven sequence of reoccurring postures through time. Current technologies enable offline pose estimation with high spatio-temporal resolution, however to understand complex behaviors, it is necessary to correlate the behavior with neuronal activity in real-time. Here we present DeepLabStream, a highly versatile, closed-loop solution for freely moving mice that can autonomously conduct behavioral experiments ranging from behavior-based learning tasks to posture-dependent optogenetic stimulation. DeepLabStream has a temporal resolution in the millisecond range, can operate with multiple devices and can be easily tailored to a wide range of species and experimental designs. We employ DeepLabStream to autonomously run a second-order olfactory conditioning task for freely moving mice and to deliver optogenetic stimuli based on mouse head-direction.

animal behavior and cognition↗

bioRxiv2017

Chronic silencing of corticothalamic layer 6 pyramidal cells affects cortical excitability and tactile behavior

Cortical projections originating in layer 6 (L6) in mouse primary somatosensory cortex have an important function controlling both cortical and sub-cortical activity. To study cortical plasticity and communication between somatosensory and motor cortex, L6-Ntsr1 cells were chronically silenced using tetanus toxin and the effect this had on cortical activity and behavior was investigated. A 2 Hz stimulation protocol was used to potentiate whisker evoked local field potentials (LFP) in a layer-dependent manner in both cortices. Silencing L6 pyramidal cells, the LFP potentiation in both cortices was affected without a change in the spontaneous multi-unit activity. Animals with L6 chronically silenced used more low-amplitude whisks, which presumably compensates for a reduction in cortical excitability. These results suggest that L6 is not only an important cortical output layer that modulates sub-cortical circuits, but also that it controls cortical dynamics.

neuroscience↗