Biology subjects

Reinhard, K.

Publications and source records attributed to Reinhard, K..

15 recordsLinked to original sources

bioRxiv2026

Visual field position shapes input sampling and output routing in the superior colliculus

Animals use the location of visual stimuli to select appropriate actions1-5, and the upper and lower visual field often carry different ecological and behavioral meaning6-9. In mice, the superior colliculus is a key central hub that transforms visual input into orienting, defensive, and approach behaviors3,10-13. Its superficial layers receive retinotopically organized input from the retina and contain genetically defined cell types with distinct downstream projections, including wide-field neurons that project to the lateral posterior thalamus and narrow-field neurons that target the parabigeminal nucleus and deeper collicular layers14-18. These features raise the question of whether circuits of the superior colliculus are repeated across visual space or exhibit visual-field-dependent specializations. Here, we show that the mouse superficial superior colliculus contains visual-field-dependent circuit modules. Dual-color rabies tracing revealed that wide-field and narrow-field neurons receive input from a largely shared set of brain regions, whereas upper- and lower-field domains differ in how they sample those inputs. Some source regions preferentially innervate one visual-field domain, producing biased regional input strength, while others contain topographically segregated projecting neurons that target upper- or lower-field domains. MAPseq showed that most superficial collicular neurons project to single downstream targets, with upper- and lower-field populations differing in target probability. Two-photon calcium imaging further showed that wide-field neurons in upper- and lower-field domains differ in stimulus selectivity. Together, these findings reveal a visual-field-dependent wiring logic that biases how the superior colliculus samples inputs and routes signals to downstream pathways. HighlightsO_LIWide- and narrow-field neurons receive broadly overlapping inputs C_LIO_LIUpper- and lower-field domains differ in input strength and topographic organization C_LIO_LIMost superficial collicular neurons project to a single target C_LIO_LIVisual field position biases downstream target probability C_LI

neuroscience↗

bioRxiv2026

Prion Protein Deficiency Results in Synaptic, Neural Network and Behavioral Alterations

The cellular form of the prion protein (PrPC) is known for its involvement in the pathogenesis of prion diseases. Recent research implicates the physiological isoform of PrP in neuronal development, excitability, and synaptic plasticity, as well as in other biological processes. However, its precise function in the development and function of neurons remains poorly understood. Here, we investigated its role during different developmental stages, both in vitro and in vivo, using different PrP knock-out (KO) mouse lines (Prnp-/-). Prion protein KO neurons cultured on microelectrode arrays (MEAs) displayed altered network dynamics compared to wild type cultures, comprising reduced burst frequency, and abnormal spike patterns, indicative of impaired maturation of the synaptic circuitry. These functional alterations were associated with a reduced expression of key presynaptic and postsynaptic proteins, including elements of the SNARE complex and regulators of excitation-inhibition balance. Similar molecular changes were also confirmed in a second Prnp-/- model, suggesting that PrPC is directly involved in these mechanisms regardless of genetic backgrounds. Alterations in neuronal networks were traceable into adulthood: in vivo recordings in adult Prnp-/- mice revealed increased neuronal responses to visual danger stimuli, which correlated with behaviorally increased fear responses to those stimuli. Together, our findings support a critical role for PrPC in the establishment and maintenance of functional neuronal networks, from early developmental stages in vitro to behaviorally mature relevant circuits in vivo, beyond genomic background. These results indicate that PrPC acts as a key regulator of synaptic development and function both in physiological and pathological conditions.

molecular biology↗

bioRxiv2025

The SAFE Labs Handbook: community-driven commitments for group leaders to improve lab culture

Creating positive and equitable lab environments has become a growing priority for the scientific community and funders of scientific research. Research institutions typically respond to this need by providing mandatory or optional training opportunities for their staff. However, there is no established resource for group leaders to improve their lab culture with concrete action points for implementation. Here, we introduce the SAFE Labs Handbook: a collection of thirty "commitments" which can be verifiably actioned without requiring institutional support. These commitments were collaboratively developed by thirteen group leaders in life sciences, from institutions across eight countries, instigated through the 2024 SAFE Labs workshop. The importance of each commitment has been scored by more than 200 researchers, at various career stages, from more than twenty countries. Even though all commitments were rated as significantly important by scientists from all career stages, implementation rates were notably low (< 25%). Lab members reported higher importance scores than group leaders, with large divergences indicating where group leaders may underestimate the potential impact on lab culture. Indeed, the overall implementation rate was correlated with importance score for group leaders, but not lab members. Strikingly, more than 95% of group leaders said they would consider implementing the handbook commitments. Given the high importance-scores and low-implementation rates, the SAFE Labs Handbook represents a unique, community-driven tool with significant potential to improve lab culture on a global scale.

scientific communication and education↗

bioRxiv2025

Ambient Light Impacts Innate Behaviors of New-World and Old-World Mice

Animals encounter predators and prey under diverse lighting conditions that signal different risks and opportunities1-4, yet how ambient illumination shapes innate approach and avoidance behaviors remains poorly understood. Here we have systematically tested the visually guided behaviors of New-World (North American Peromyscus) and Old-World (Eurasian Mus) mice under conditions mimicking bright daylight or dim moonlit environments. We identified common and species-specific adaptations to the different lighting conditions. Across species, dim light enhanced the speed and vigor of escape responses to predator-like looming stimuli. However, species diverged in their reactions to non-threatening stimuli, with Mus musculus and Peromyscus polionotus increasing aversive behaviors under dim light, while Peromyscus maniculatus showed stronger avoidance under bright conditions. Finally, although ambient light levels had a common effect on exploratory behavior, these changes were not predictive of subsequent visually evoked behaviors. Our findings reveal that ambient lighting profoundly and differentially shapes innate behavioral strategies across species, and demonstrate that these context-specific survival responses are inherited rather than learned.

neuroscience↗

bioRxiv2025

Dendritic Architecture Enables de Novo Computation of Salient Motion in the Superior Colliculus

Dendritic architecture plays a crucial role in shaping how neurons extract behaviorally relevant information from sensory inputs. Wide-field neurons in the superior colliculus integrate visual information from the retina to encode cues critical for visually guided orienting behaviors. However, the principles governing how these neurons filter their inputs to generate appropriate responses remain unclear. Using viral tracing, two-photon calcium imaging, and computational modeling, we show that wide-field neurons receive functionally diverse inputs from twelve retinal ganglion cell types, forming a layered, type-specific organization along their dendrites. This structured arrangement allows wide-field neurons to multiplex salient motion cues, selectively amplifying movement and suppressing static features. Computational models reveal that the spatial organization of dendrites and inputs enables the selective extraction of behaviorally relevant stimuli, including de novo computations. Our findings underscore the critical role of dendritic architecture in shaping sensory processing and neural circuit function.

neuroscience↗

bioRxiv2025

Predicting the Regenerative Potential of Retinal Ganglion Cells Based on Developmental Growth Trajectories

Retinal ganglion cells in the mammalian central nervous system fail to regenerate following injury, with the capacity to survive and regrow varying by cell type. This variability may be linked to differences in developmental programs that overlap with the genetic pathways that mediate regeneration. To explore this correlation, we compared the structural changes in mouse retinal ganglion cells during development with those occurring after axonal injury. The dendritic trees of over 1,000 ganglion cells were reconstructed at different developmental stages, revealing that each cell type follows a distinct timeline. ON-sustained (sON) cells reach maturity by P14, whereas ON-transient (tON) cells achieve their maximum dendritic size by P10. Modeling of the dendritic changes indicate that while sON and tON follow similar growth programs the onset of growth was later in sON. After optic nerve crush, the remodeling of dendritic architecture differed between the two cell-types. sON cells exhibited rapid dendritic shrinkage, while tON cells shrank more gradually with changes in branching features. Following injury, sON cells reverted to an earlier developmental state than tON cells. In addition, after co-deletion of PTEN and SOC3, neurons appeared to regress further back in developmental time. Our results provide evidence that a ganglion cells resilience to injury and regenerative potential is predicted by its maturation timeline. Understanding these intrinsic differences could inform targeted neuroprotective interventions.

neuroscience↗

bioRxiv2025

Exploring the Pathogen Profiles of Ancient Feces

Analysis of ancient desiccated feces - termed paleofeces or coprolites - can unlock insights into the lives of ancient people. We collected desiccated feces from caves in the Rio Zape Valley in Mexico (725-920 CE). First, we extracted DNA with methods previously optimized for paleofeces. Then, we applied highly sensitive modern molecular tools (i.e., PCR pre-amplification followed by multi-parallel qPCR) to assess the presence of 30 enteric pathogens. We detected [≥]1 pathogen associated gene in each of the ten samples and a mean of 3.9 pathogens per sample. The targets detected included Blastocystis spp. (n=7), atypical enteropathogenic E. coli (n=7), Enterobius vermicularis (n=6), Entamoeba spp. (n=5), enterotoxigenic E. coli (n=5), Shigella spp./enteroinvasive E. coli (n=3), Giardia spp. (n=2), and E. coli O157:H7 (n=1). The protozoan pathogens we detected (i.e., Giardia spp. and Entamoeba spp.) have been previously detected in paleofeces via enzyme-linked immunoassay (ELISA), but have not via PCR. This work represents the first detection of Blastocystis spp. atypical enteropathogenic E. coli, enterotoxigenic E. coli, Shigella spp./enteroinvasive E. coli, and E. coli O157:H7 in paleofeces. These results suggest that sensitive modern molecular tools, such as PCR, can be used to evaluate ancient materials for genes of interest.

microbiology↗

bioRxiv2024

Full-length Cryptochrome 1 in the outer segments of the retinal blue cone photoreceptors in humans and great apes suggests a role beyond transcriptional repression

Mammalian cryptochrome 1 (CRY1) is a central player in the circadian transcription-translation feedback loop, crucial for maintaining a roughly 24-hour rhythm. CRY1 was suggested to also function as blue-light photoreceptor in humans and has been found to be expressed at the mRNA level in various cell types of the inner retina. However, attempts to detect CRY1 at the protein level in the human retina have remained unsuccessful so far. Using various C-terminal specific antibodies recognizing full-length CRY1 protein, we consistently detected selective labelling in the outer segments of short wavelength-sensitive (SWS1, "blue") cone photoreceptor cells across human, bonobo, and gorilla retinae. No other retinal cell types were stained, which is in contrast to what would be expected of a ubiquitous clock protein. Subcellular fractionation experiments in transfected HEK cells using a C-terminal specific antibody located full-length CRY1 in the cytosol and membrane fractions. Our findings indicate that human CRY1 has several different functions including at least one non-clock function. Our results also raise the likely possibility that several different versions of CRY1 exists in humans. We suggest that truncation of the C-terminal tail, maybe to different degrees, may affect the localization and function of human CRY1.

cell biology↗

bioRxiv2023

The neural basis of defensive behaviour evolution in Peromyscus mice

Evading imminent predator threat is critical for survival. Effective defensive strategies can vary, even between closely related species. However, the neural basis of such species-specific behaviours is still poorly understood. Here we find that two sister species of deer mice (genus Peromyscus) show different responses to the same looming stimulus: P. maniculatus, which occupy densely vegetated habitats, predominantly dart to escape, while the open field specialist, P. polionotus, pause their movement. This difference arises from species-specific escape thresholds, is largely context-independent, and can be triggered by both visual and auditory threat stimuli. Using immunohistochemistry and electrophysiological recordings, we find that although visual threat activates the superior colliculus in both species, the role of the dorsal periaqueductal gray (dPAG) in driving behaviour differs. While dPAG activity scales with running speed and involves both excitatory and inhibitory neurons in P. maniculatus, the dPAG is largely silent in P. polionotus, even when darting is triggered. Moreover, optogenetic activation of excitatory dPAG neurons reliably elicits darting behaviour in P. maniculatus but not P. polionotus. Together, we trace the evolution of species-specific escape thresholds to a central circuit node, downstream of peripheral sensory neurons, localizing an ecologically relevant behavioural difference to a specific region of the complex mammalian brain.

neuroscience↗

bioRxiv2022

Pathway-specific inputs to the superior colliculus support flexible triggering of innate behaviors

Behavioral flexibility requires the ability to modify the feedforward transmission of sensory information. The superior colliculus mediates visually guided innate defensive behaviors via cell-type specific projections. However, how brain-wide inputs to the superior colliculus are organized to modulate visual processing and enable flexible behavior remains unknown. To determine these rules, we focused on inhibitory projection (Gad2) neurons. Trans-synaptic tracing and neuronal recordings revealed that Gad2 neurons projecting to the dorsal lateral geniculate nucleus (LGd) and the parabigeminal nucleus (PBG) form two separate anatomical and functional populations, where each circuit received a different set of non-retinal inputs. Inhibiting LGd or PBG projecting Gad2 neurons resulted in opposing effects on behavior; increasing freezing or escape probability to visual looming stimuli, respectively. These data suggest that projection-specific sampling of brain-wide inputs provide a circuit design principle that enables feed-forward transfer of visual threat to be independently adjusted to produce context specific behavior.

neuroscience↗

bioRxiv2020

Brain-wide mapping of neural activity mediating collicular-dependent behaviors

Neuronal cell-types are arranged in brain-wide circuits to guide behavior. In mice, the superior colliculus is comprised of a set of cell-types that each innervate distinct downstream targets. Here we reveal the brain-wide networks downstream of four collicular cell-types by combining functional ultrasound imaging (fUSi) with optogenetics to monitor neural activity at a resolution of ~100 m. Each neuronal group triggered different behaviors, and activated distinct, partially overlapping sets of brain nuclei. This included regions not previously thought to mediate defensive behaviors, e.g. the posterior paralaminar nuclei of the thalamus (PPnT), that we show to play a role in suppressing habituation. Electrophysiological recordings support the fUSi findings and show that neurons in the downstream nuclei preferentially respond to innately threatening visual stimuli. This work provides insight into the functional organization of the networks governing defensive behaviors and demonstrates an experimental approach to explore the whole-brain neuronal activity downstream of targeted cell-types.

neuroscience↗

bioRxiv2019

CoproID predicts the source of coprolites and paleofeces using microbiome composition and host DNA content

Shotgun metagenomics applied to archaeological feces (paleofeces) can bring new insights into the composition and functions of human and animal gut microbiota from the past. However, paleofeces often undergo physical distortions in archaeological sediments, making their source species difficult to identify on the basis of fecal morphology or microscopic features alone. Here we present a reproducible and scalable pipeline using both host and microbial DNA to infer the host source of fecal material. We apply this pipeline to newly sequenced archaeological specimens and show that we are able to distinguish morphologically similar human and canine paleofeces, as well as non-fecal sediments, from a range of archaeological contexts.

microbiology↗

bioRxiv2019

What your eye tells your brain

The retinal output is the sole source of visual information for the brain. Studies in non-primate mammals estimate that this information is carried by several dozens of retinal ganglion cell types, each informing the brain about different aspects of a visual scene. Even though morphological studies of primate retina suggest a similar diversity of ganglion cell types, research has focused on the function of only a few cell types. In human retina, recordings from individual cells are anecdotal or focus on a small subset of identified types. Here, we present the first systematic ex-vivo recording of light responses from 342 ganglion cells in human retinas obtained from donors. We find a great variety in the human retinal output in terms of preferences for positive or negative contrast, spatio-temporal frequency encoding, contrast sensitivity, and speed tuning. Some human ganglion cells showed similar response behavior as known cell types in other primates, while we also recorded light responses that have not been described previously. This first extensive description of the human retinal output should facilitate interpretation of primate data and comparison to other mammalian species, and it lays the basis for the use of ex-vivo human retina for in-vitro analysis of novel treatment approaches.

neuroscience↗

bioRxiv2019

The Prevotella copri complex comprises four distinct clades that are underrepresented in Westernised populations

Prevotella copri is a common inhabitant of the human gut. Interest in P. copri has gathered pace due to conflicting reports on whether it is beneficial or detrimental to health. In a cross-continent meta-analysis exploiting >6,500 available metagenomes supported by new isolate sequencing and recovery of high-quality genomes from metagenomes, we obtained >1,000 P. copri genomes. This 100-fold increase over existing isolate genomes allowed the genetic and global population structure of P. copri to be explored at an unprecedented depth. We demonstrate P. copri is not a monotypic species, but encompasses four distinct clades (>10% inter-clade vs. <4% intra-clade average single nucleotide variants) for which we propose the name P. copri complex, comprising clades A, B, C and D. We show the complex is near ubiquitous in non-Westernised populations (95.4% versus 29.6% in Westernised populations), where all four clades are typically co-present within an individual (61.6% of the cases), in contrast to Westernised populations (4.6%). Genomic analysis of the complex reveals substantial and complementary functional diversity, including the potential for utilisation of complex carbohydrates, suggestive that multi-generational dietary modifications may be a driver for the reduced P. copri prevalence in Westernised populations. Analysis of ancient stool microbiomes highlights a similar pattern of P. copri presence consistent with modern non-Westernised populations, allowing us to estimate the time of clade delineation to pre-date human migratory waves out of Africa. Our analysis reveals P. copri to be far more diverse than previously appreciated and this diversity appears to be underrepresented in Western-lifestyle populations.

microbiology↗

bioRxiv2018

Target specific routing of visual information by the superior colliculus

Using sensory information to trigger different behaviours relies on circuits that pass-through brain regions. However, the rules by which parallel inputs are routed to different downstream targets is poorly understood. The superior colliculus mediates a set of innate behaviours, receiving input from ~30 retinal ganglion cell types and projecting to behaviourally important targets including the pulvinar and parabigeminal nucleus. Combining transsynaptic circuit tracing with in-vivo and ex-vivo electrophysiological recordings we observed a projection specific logic where each collicular output pathway sampled a distinct set of retinal inputs. Neurons projecting to the pulvinar or parabigeminal nucleus uniquely sampled 4 and 7 cell types, respectively. Four others innervated both pathways. The visual response properties of retinal ganglion cells correlated well with those of their disynaptic targets. These findings suggest that projection specific sampling of retinal inputs forms a mechanistic basis for the selective triggering of visually guided behaviours by the superior colliculus.

neuroscience↗