Biology subjects

Meinhardt, M.

Publications and source records attributed to Meinhardt, M..

4 recordsLinked to original sources

bioRxiv2026

Preliterate symbolic language processing sets the neural stage for learning to read

Formal writing is evolutionarily recent, yet the brains of literate adults contain regions - the OTS-words subregions - that respond more strongly to written text than other stimuli. We tested a novel solution to this multi-disciplinary paradox: Does symbolic language processing, which emerged early in human history, lay the neural foundation for reading? In a longitudinal fMRI study, we followed 17 children through their first year of literacy training and related neural responses to text, symbolic language processing, and emerging reading skills over time. We found that middle OTS-words is engaged in symbolic language processing before children learn to read, and that this early engagement predicts later text selectivity and reading ability. These findings suggest that literacy builds on a pre-existing neural scaffold linking vision and language.

neuroscience↗

bioRxiv2022

Less is more - loss of EGFL7 improves memory by upregulation of VEGF-D

Neural stem cells reside in a specialized neurogenic niche of the hippocampus termed the subgranular zone. Throughout life, they give rise to adult-born neurons in the dentate gyrus thereby contributing to learning and memory. Here, we report that neurons together with neural stem and precursor cells secrete the neurovascular protein epidermal growth factor-like protein 7 (EGFL7) to shape this niche. EGFL7 knock-out in vivo promoted adult neurogenesis generating neurons forming additional spines which permanently integrated into the neural circuit until old age. RNA-sequencing identified the cytokine VEGF-D as a major molecular driver of this process in vivo. In behavioral studies EGFL7 knock-out mice displayed stronger maintenance of memory suggesting longer-lasting spatial memory and improved memory consolidation in the hippocampus by modulation of pattern separation in young and aged mice. Taken together, EGFL7 is an upstream regulator of the VEGF-D in adult neurogenesis and a key regulator of learning and memory.

neuroscience↗

bioRxiv2020

Adverse Social Experiences in Adolescent Rats Results in Persisting Sex-Dependent Effects on Alcohol-Seeking Behavior

BackgroundAccumulating clinical evidence suggests women with prior exposure to adverse childhood experiences are more susceptible to alcohol relapse and other health-related issues. Yet, preclinical studies investigating sex-dependent effects of adolescent adverse social experiences (ASEs) on later alcohol-seeking behavior are lacking. This is mainly due to a lack of valid animal models and a shortage of studies comparing sexes. Therefore, we sought to investigate the sex-dependent effects of ASE on adult alcohol-seeking behavior, locomotion and reward sensitivity in both male and female rats. MethodsWe recently developed a rat model for adolescent peer-rejection which allows us to study the long-term consequences of ASEs. Peer-rejection interferes with adolescent rats ability to engage in adequate and reciprocal play behaviors that result in persistent dysregulation of social and pain-related behavior. Adolescent Wistar rats were reared from postnatal day (pd) 21 to pd 50 either within a group of Fischer 344 rats (ASE) or with Wistar rats (control). Adult male and female rats were tested in the reinstatement paradigm for cue-induced alcohol-seeking behavior, circadian locomotor activity, and sucrose consumption in adulthood long-after the termination of the peer-rejection condition. ResultsPeer-rejection induced persistent sex-dependent changes to cue-induced reinstatement. Females showed an increased reinstatement effect while peer-rejected males demonstrated a decrease. No differences were observed in circadian locomotor activity or reward sensitivity to sucrose. ConclusionsPeer-rejection has lasting sex-dependent consequences on alcohol-seeking behavior without affecting locomotion or sweet reward sensitivity. Our results suggest that peer-rejected female rats represent a vulnerable population to study relapse-like behaviors similar to clinical findings. While males seem to buffer the peer-rejection effect and demonstrate resilience to later-life alcohol-seeking behaviors, measured by the reinstatement effect. Finally, we provide a novel approach to investigate the molecular and neurobiological underpinnings of ASEs on alcohol and other drug-seeking behaviors.

neuroscience↗

bioRxiv2017

Deep Sequencing Reveals Transient Segregation of T Cell Repertoires in Splenic T Cell Zones During an Immune Response

Immunological differences between hosts, such as diverse T-cell receptor (TCR) repertoires, are widely credited for reducing the risk of pathogen spread and adaptation in a population. Within-host immunological diversity might likewise be important for robust pathogen control, but to what extent naive TCR repertoires differ across different locations in the same host is unclear. T-cell zones (TCZs) in secondary lymphoid organs provide secluded micro-environmental niches. By harboring distinct TCRs, such niches could enhance within-host immunological diversity. On the other hand, rapid T cell migration is expected to dilute such diversity. Here, we combined tissue micro-dissection and deep sequencing of the TCR {beta} chain to examine the extent to which TCR repertoires differ between TCZs in murine spleens. In the absence of antigen, we found little evidence for differences between different TCZs of the same spleen. Yet, three days after immunization with sheep red blood cells, we observed a >10-fold rise in the number of clones that appeared to localize to individual zones. Remarkably, these differences largely disappeared at 4 days after immunization, when hallmarks of an ongoing immune response were still observed. These data suggest that in the absence of antigen, any repertoire differences observed between TCZs of the same host can largely be attributed to random clone distribution. Upon antigen challenge, segregated TCR compartments appear and disappear within days. Such \"transient mosaic\" dynamics could be an important barrier for pathogen adaptation and spread during an immune response.

immunology↗