Biology subjects

Franke, F.

Publications and source records attributed to Franke, F..

11 recordsLinked to original sources

bioRxiv2026

Magel2 deficiency drives microglial synaptic engulfment and alters neuron-microglia interactions in Prader-Willi syndrome

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder characterized by hypothalamic dysfunction, developmental delay, hyperphagia, and cognitive impairment, yet the cellular mechanisms underlying circuit abnormalities remain unclear. Here, we show that loss of the imprinted gene Magel2 remodels microglial state and function in a mouse model of PWS. Three-dimensional morphometric analysis of hypothalamic microglia revealed reduced structural complexity and contracted territorial domains, emerging early in development and largely independent of obesity. Single-nucleus RNA sequencing of hypothalamic brain tissue identified extensive transcriptional reprogramming involving immune signaling, cellular communication, ribosome function, synaptic organization, and protein translation, with stronger effects in females. Magel2 deficiency also increased microglia-neuron contacts and synaptic engulfment, accompanied by reduced synaptic marker density, suggesting aberrant refinement of hypothalamic circuits. Analyses of human post-mortem hypothalamic tissue from individuals with PWS confirmed microglial structural alterations and increased complement engagement. Ligand-receptor inference further revealed reorganization of microglia-centered communication networks, including altered adhesion, trophic, and immune signaling consistent with enhanced phagocytic states. Together, these findings identify microglial remodeling and increased synaptic engagement as central features of Magel2 deficiency, implicate microglia in hypothalamic circuit dysfunction in PWS, and highlight excessive synaptic pruning as a novel dysfunctional mechanism of PWS.

neuroscience↗

bioRxiv2026

Rapid estimation of receptive fields across stages of the early visual system

Estimating receptive fields in large neural populations is often limited by experimental time: stimuli with theoretically favorable statistics for receptive-field estimation may, in practice, evoke too few informative spikes in neurons with high specificity for structured features, requiring impracticably long recordings. Therefore, we asked whether a structured stimulus could broadly engage neural populations across stages of the early visual system while permitting a tractable and interpretable reverse-correlation analysis. To address this question, we developed "reverse correlation against stimulus elements (RCASE)", an analysis framework for stimuli that can be represented frame by frame through the presence or absence of specific stimulus elements. We then designed such a stimulus consisting of random moving objects (RMO) and compared RMO/RCASE with conventional spike-triggered averaging using a dense binary white noise (WN/STA) stimulus across different stages of the early visual system of the mouse, namely the retina, the nucleus of the optic tract, the superior colliculus and the primary visual cortex, and in the primate retina. To distinguish the contributions of spatial and temporal scales, motion, stimulus structure, and analysis choice, we additionally compared against WN/STA with different square sizes and frame rates, spike-triggered covariance analysis, as well as random static objects and spatially correlated cloud stimuli. RMO evoked stronger and more reliable responses than WN in the mouse retina and across the investigated mouse visual areas. RMO/RCASE yielded discernible receptive fields for a substantially larger proportion of neurons and in a fraction of the recording time. Although the stimulus objects featured localized moving contrast edges, this advantage was not restricted to direction-selective cell populations. In the primate retina, in contrast, WN/STA approached the performance of RMO/RCASE. RMO/RCASE also supported simultaneous estimation of stimulus direction, speed, and color tuning. Our approach enables rapid and interpretable functional characterization of large populations of visual neurons, enabling to simultaneously recover receptive fields and feature tuning, whenever a low-dimensional feature space can be specified beforehand.

neuroscience↗

bioRxiv2026

Mice and humans use ambiguous local motion to stabilize gaze

Animals need to infer properties of the environment that are only ambiguously encoded by neurons in the sensory periphery. In vision, local edge motion seen through small receptive fields does not uniquely specify the direction of global or object motion. Can these ambiguous local motion signals drive behavior directly, or must the ambiguity first be resolved? We addressed this question in reflexive gaze stabilization by tracing motion signals from the retina through the nucleus of the optic tract (NOT) to eye movements, combining retinal and in vivo electrophysiology, computational modelling, and eye tracking in mice and humans. By using stimuli that dissociate local edge motion from global, object motion, we found that NOT cell responses were strongly biased towards local motion and were largely explained by linear pooling of retinal inputs. This effect propagated to behavior: eye movements followed local motion, to the point that changing the edge orientation of vertically moving objects produced horizontal eye movements. Humans showed a qualitatively similar bias, which increased when central vision was masked. Thus, ambiguous local motion signals can drive effective behavior; a conserved sensorimotor strategy in which visually guided behavior relies on a heuristic rather than an accurate reconstruction of the external world.

neuroscience↗

bioRxiv2025

Direction-selective retinal ganglion cells encode motion direction uniformly, despite having discretely distributed cardinal preferences

On-Off direction-selective retinal ganglion cells (DS RGCs) exhibit broad tuning curves, responding robustly to motion aligned with or near their preferred direction. These cells comprise four major subtypes, each tuned to motion along one of the four cardinal axes: nasal, superior, temporal, or inferior. However, natural stimuli can move in any direction, and it remains unclear whether intermediate directions are encoded less effectively, or whether this cardinal organization nevertheless supports uniform direction encoding. Here, we combined previous electrophysiological recordings with an information-theoretic measure, the Stimulus Specific Information, to estimate the directional sensitivity of small populations of recorded neurons. This analysis revealed that DS RGC populations are uniformly sensitive across all directions of motion. We then asked whether the observed homogeneous sensitivity was a consequence of DS RGCs maximizing the average stimulus information. Simulations with artificially modified tuning curve widths revealed that DS cells prioritize avoiding pronounced drops in sensitivity over maximizing the average transmitted Information. Maximizing this minimal sensitivity may therefore be a principle to understand the organization of sensory systems.

neuroscience↗

bioRxiv2025

FOXP1 differentially regulates the development of murine vasopressin and oxytocin magnocellular neurons

The neuropeptides arginine vasopressin (AVP) and oxytocin (OXT) are closely related. As neurohormones, AVP and OXT are mainly produced in magnocellular neurons (MCNs) located in the hypothalamus. Development of both neuron types requires coordinated expression of transcription factors OTP, SIM1, ARNT2 and POU3F2. However, the exact transcription factors involved in the diferential diferentiation of the AVP and OXT lineages are yet unknown. We used a publicly available single-cell RNA-sequencing dataset of the developing mouse hypothalamus to identify gene regulatory networks linked to AVP and OXT neuronal diferentiation. We identified RORA, EBF3, FOXP1, FOXP2, and BCL11B as transcription factors with possible relevance for Avp and Oxt MCN divergence. We then modeled developmental gene expression dynamics using computational cell fate mapping. This revealed enrichment of EBF3 and BCL11B in the Avp lineage, while FOXP1 and FOXP2 are enriched in the Oxt lineage. Next, in silico analysis of Avp and Oxt promoters found predicted binding sites for FOXP1 and FOXP2 in the Oxt promoter, suggesting a role in Oxt MCN diferentiation. Finally, we validated the role of one candidate (FOXP1) with a heterozygous knockout mouse line. Compared to wild-type littermates, we find decreased AVP and OXT neuron abundance, with OXT neurons disproportionally afected.

neuroscience↗

bioRxiv2024

Action potential propagation speed compensates for traveling distance in the human retina

Neural information processing requires accurately timed action potentials arriving from presynaptic neurons at the postsynaptic neuron. However, axons of ganglion cells in the human retina feature low axonal conduction speeds and vastly different lengths, which poses a challenge to the brain for constructing a temporally coherent image over the visual field. Combining results from microelectrode array recordings, human behavioral measurements, transmission electron microscopy, and mathematical modelling of the retinal nerve fiber layer, we demonstrate that axonal propagation speeds compensate for variations in axonal length across the human retina including the fovea. The human brain synchronizes the arrival times of action potentials at the optic disc by increasing the diameters of longer axons, which increases their propagation speeds.

neuroscience↗

bioRxiv2023

A detailed input-output characterization of single neurons reveals the synaptic basis of spontaneous spiking in recurrent networks

Self-sustained recurrent activity in cortical networks is thought to be important for multiple crucial processes, including circuit development and homeostasis. Yet, the precise relationship between synaptic input patterns and the spiking output of individual neurons remains largely unresolved. Here, we developed, validated and applied a novel in vitro experimental platform and analytical procedures that provide - for individual neurons - simultaneous excitatory and inhibitory synaptic activity estimates during recurrent network activity. Our approach combines whole-network high-density microelectrode array (HD-MEA) recordings from rat neuronal cultures with patch clamping and enables a comprehensive mapping and characterization of active incoming connections to single postsynaptic neurons. We found that, during network states with excitation(E)-inhibition(I) balance, postsynaptic spiking often coincided with the maxima of fast fluctuations in the input E/I ratio. These spike-associated E/I ratio escalations were largely due to a rapid bidirectional change in synaptic inhibition that was modulated by the network-activity level. Our approach also uncovered the underlying circuit architecture and we show that individual neurons received a few key inhibitory connections - often from special hub neurons - that were instrumental in controlling postsynaptic spiking. Balanced network theory predicts dynamical regimes governed by small and rapid input fluctuation and featuring a fast neuronal responsiveness. Our findings - obtained in self-organized neuronal cultures - suggest that the emergence of these favorable regimes and associated network architectures is an inherent property of cortical networks in general.

neuroscience↗

bioRxiv2022

Spatial variation in red deer density in relation to forest disturbance and ungulate management in a transboundary forest ecosystem

1. ContextForests in Europe are exposed to increasingly frequent and severe disturbances. The resulting changes in the structure and composition of forests can have profound consequences for the wildlife inhabiting them. Moreover, wildlife populations in Europe are often subjected to differential management regimes as they regularly extend across multiple national and administrative borders. The red deer (Cervus elaphus) population in the Bohemian Forest Ecosystem, straddling the Czech-German border, has experienced forest disturbances, primarily caused by windfalls and bark beetle (Ips typographus) outbreaks during the past decades. To adapt local management strategies to the changing environmental conditions and to coordinate them across the international border, reliable estimates of red deer density and abundance are highly sought-after by policymakers, wildlife managers, and stakeholders. 2. Approach and MethodsCovering a 1081-km2 study area, we conducted a transnational non-invasive DNA sampling study in 2018 that yielded 1578 genotyped DNA samples from 1120 individual red deer. Using spatial capture-recapture models, we estimated total and jurisdiction-specific abundance of red deer throughout the ecosystem and quantified the role of forest disturbance and differential management strategies in shaping spatial heterogeneity in red deer density. We hypothesized that (a) forest disturbances provide favourable habitat conditions (e.g., forage and cover), and (b) contrasting red deer management regimes in different jurisdictions create a differential risk landscape, ultimately shaping density distributions. 3. ResultsOverall, we estimated that 2851 red deer (95% Credible Intervals = 2609 - 3119) resided in the study area, with a relatively even overall sex ratio (1406 females, 1229 - 1612 and 1445 males, 1288 - 1626). The average red deer density was higher in Czechia (3.5 km-2, 1.2 - 12.3) compared to Germany (2 km-2, 0.2 - 11). The effect of forest disturbances on red deer density was context dependent. Forest disturbances had a positive effect on red deer density at higher elevations and a negative effect at lower elevations, which could be explained by partial migration and its drivers in this population. Density of red deer was generally higher in management units where hunting is prohibited. In addition, we found that sex ratios differed between administrative units and were more balanced in the non-intervention zones. 4. Synthesis and applicationsOur results show that the effect of forest disturbances on wild ungulates is modulated by additional factors, such as elevation and ungulate management practices. Overall density patterns and sex ratios suggested strong gradients in density between administrative units. With climate change increasing the severity and frequency of forest disturbances, population-level monitoring and management are becoming increasingly important especially for wide-ranging species as both wildlife and global change transcend administrative boundaries.

ecology↗

bioRxiv2020

Retinal mechanisms of saccadic suppression and their role in processing sequential stimuli

Visual perception remains stable across saccadic eye movements, despite the concurrent strongly disruptive visual flow. This stability is partially associated with a reduction in visual sensitivity, known as saccadic suppression, which already starts in the retina with reduced ganglion cell sensitivity. However, the retinal circuit mechanisms giving rise to such suppression remain unknown. Here, we describe these mechanisms using electrophysiology in mouse, pig, and macaque retina, 2-photon calcium imaging, computational modeling, and human psychophysics. We find that sequential stimuli, such as those that naturally occur during saccades, trigger three independent suppressive mechanisms in the retina. The main suppressive mechanism is triggered by contrast-reversing sequential stimuli and originates within the receptive field center of ganglion cells. It does not involve inhibition or other known suppressive mechanisms such as saturation or adaptation. Instead, it relies on temporal filtering of the inherently slow response of cone photoreceptors coupled with downstream nonlinearities. Two further mechanisms of suppression are present predominantly in ON ganglion cells and originate in the receptive field surround, highlighting a novel disparity between ON and OFF ganglion cells. The mechanisms uncovered here likely play a role in shaping the retinal output following eye movements and other natural viewing conditions where sequential stimulation is ubiquitous.

neuroscience↗

bioRxiv2019

Massively Parallel Microwire Arrays Integrated with CMOS chips for Neural Recording

Multi-channel electrical recordings of neural activity in the brain is an increasingly powerful method revealing new aspects of neural communication, computation, and prosthetics. However, while planar silicon-based CMOS devices in conventional electronics scale rapidly, neural interface devices have not kept pace. Here, we present a new strategy to interface silicon-based chips with three-dimensional microwire arrays, providing the link between rapidly-developing electronics and high density neural interfaces. The system consists of a bundle of microwires mated to large-scale microelectrode arrays, such as camera chips. This system has excellent recording performance, demonstrated via single unit and local-field potential recordings in isolated retina and in the motor cortex or striatum of awake moving mice. The modular design enables a variety of microwire types and sizes to be integrated with different types of pixel arrays, connecting the rapid progress of commercial multiplexing, digitisation and data acquisition hardware together with a three-dimensional neural interface.

neuroscience↗

bioRxiv2019

Saccadic suppression by way of retinal-circuit image processing

Visual sensitivity, probed through perceptual detectability of very brief visual stimuli, is strongly impaired around the time of rapid eye movements. This robust perceptual phenomenon, called saccadic suppression, is frequently attributed to active suppressive signals that are directly derived from eye movement commands. Here we show instead that visual-only mechanisms, activated by saccade-induced image shifts, can account for all perceptual properties of saccadic suppression that we have investigated. Such mechanisms start at, but are not necessarily exclusive to, the very first stage of visual processing in the brain, the retina. Critically, neural suppression originating in the retina outlasts perceptual suppression around the time of saccades, suggesting that extra-retinal movement-related signals, rather than causing suppression, may instead act to shorten it. Our results demonstrate a far-reaching contribution of visual processing mechanisms to perceptual saccadic suppression, starting in the retina, without the need to invoke explicit motor-based suppression commands.

neuroscience↗