Biology subjects

Kohl, J.

Publications and source records attributed to Kohl, J..

9 recordsLinked to original sources

bioRxiv2025

Overnight circuit remodelling drives juvenile alloparental care

Parental care is critical for the survival of altricial young and is mediated by neural circuits that are well characterised in adult rodents. Although adults can exhibit caregiving even before becoming parents, the developmental origins of this so-called alloparental behaviour remain unclear. Here, we show that alloparental behaviour in mice emerges abruptly between postnatal day (P)14 and 15, independently of prior social experience. This behavioural transition coincides with the onset of pup-specific activity in galanin-expressing medial preoptic area (MPOAGal) neurons, which are essential for parental behaviour in adulthood. Chemogenetic silencing of MPOAGal neurons abolishes caregiving in juveniles, suggesting that similar circuits control parenting across life stages. Viral trans-synaptic tracing and whole-cell recordings reveal extensive input remodelling of MPOAGal neurons between P14 and 15, marking a rapid transition from a highly connected, immature network to a sparser, adult-like circuit configuration. We identify microglia as key mediators of this process, as their ablation prevents both synaptic reorganisation and the emergence of alloparenting. Together, these findings uncover a previously unrecognised, microglia-dependent developmental switch that enables caregiving in juveniles through rapid circuit reconfiguration.

neuroscience↗

bioRxiv2024

Integration of hunger and hormonal state gates infant-directed aggression

Social behaviour is profoundly shaped by internal physiological states. While significant progress has been made in understanding how individual states such as hunger, stress, or arousal modulate behaviour, animals experience multiple states at any given time. The neural mechanisms that integrate such orthogonal states--and how this integration affects behaviour--remain poorly understood. Here we report how hunger and estrous state converge on neurons in the medial preoptic area (MPOA) to shape infant-directed behaviour. We find that hunger promotes pup-directed aggression in normally non-aggressive virgin female mice. This behavioural switch occurs through inhibition of MPOA neurons, driven by the release of neuropeptide Y (NPY) from Agouti-related peptide-expressing neurons in the arcuate nucleus (ArcAgRP neurons). The propensity for hunger-induced aggression is set by reproductive state, with MPOA neurons detecting changes in progesterone (P4) to estradiol (E2) ratio across the estrous cycle. Hunger and estrous state converge on HCN (hyperpolarization-activated cyclic nucleotide-gated) channels, which sets the baseline activity and excitability of MPOA neurons. Using micro-endoscopic imaging, we confirm these findings in vivo, revealing that MPOA neurons encode a state for pup-directed aggression. This work thus provides a mechanistic understanding of how multiple physiological states are integrated to flexibly control social behaviour.

neuroscience↗

bioRxiv2023

Brain-wide activity-identity mapping of neural networks associated with prosocial motivation in rats

A prosocial response to others in distress is an important driver of behavior across social species. To investigate the neurobiological mechanism leading to prosocial behavior, we use a helping behavior test wherein rats may release a trapped conspecific by opening a restrainer door. To ensure rats were not acting for social interaction, a separation divider prevented post-release contact ("separated" test). Despite the divider, most rats consistently opened the restrainer, demonstrating prosocial motivation. Brain-wide c-Fos analysis conducted via our opensource software "Brainways", revealed activity in empathy-related regions, including the anterior cingulate and insular cortices. Nucleus accumbens activity, previously recorded during helping, was not significant in the "separated" test. Chemogenetic manipulations of the accumbens did not prevent helping, suggesting that its activity reflects contact seeking. Mapping of oxytocin and dopamine receptors on active cells revealed region-specific recruitment of these subpopulations, depending on the social context. Network connectivity analysis highlights context-dependent functional subcircuits.

neuroscience↗

bioRxiv2023

From amplicons to strains: The limitations of metabarcoding as criterium in the selection process of biocontrol strains against the pome fruit pathogen Neonectria ditissima

European canker, caused by the fungal pathogen Neonectria ditissima, causes severe economic losses in apple production and conventional control measures are not sufficiently effective. Recently, parts of the endophyte community have been suggested to play a role in the response of the host to the pathogen, potentially leading to higher resistance of apple cultivars to disease outbreaks. In addition, advances on biologically controlling the disease have been booked by the application of fungi isolated at the boundary of cankered and healthy wood tissue. In this study we sought to evaluate if and how metabarcoding analysis can support decisions on selection of biological control agents in a two-steps process: first we profiled fungal and bacterial taxa using Illumina MiSeq sequencing on branches of potted apple trees that had been inoculated with either water or a suspension of N. ditissima spores. We combined the knowledge on the metataxonomic profile with quantitative data on the N. ditissima branch colonisation (with relative abundances and absolute TaqMan qPCR concentrations) to identify taxa that show negative or positive correlations with N. ditissima DNA concentration. Secondly, we compared our fungal metataxonomic profile to the ITS amplicons of fungal isolates that had been tested for biocontrol potential in bioassays in a previous study. The aim was to possibly link fungal taxa with proven efficacy against the pathogen to the microbiome composition. The only ASVs showing a consistent negative correlation to relative and absolute N. ditissima abundance belonged to the bacterial genera Kineococcus and Hymenobacter. For fungal taxa only N. ditissima itself positively correlated to its increasing abundance, albeit only by rank and neither linearly nor beta binomially. Sequences belonging to the most promising antagonists from the study by Elena et al. (2022) could not be detected in the fungal microbiome profile at all. In addition, the combination of short reads length and high conservation within the chosen amplicon resulted in insufficient resolution to differentiate between a range of different efficacies of isolates belonging to the same genus (i.e. Aureobasidium).

microbiology↗

bioRxiv2022

Targeting C5aR1 signaling reduced neutrophil extracellular traps and ameliorates COVID-19 pathology

Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that complement component 5a (C5a), through its cellular receptor C5aR1, has potent proinflammatory actions, and plays immunopathological roles in inflammatory diseases, we investigated whether C5a/C5aR1 pathway could be involved in COVID-19 pathophysiology. C5a/C5aR1 signaling increased locally in the lung, especially in neutrophils of critically ill COVID-19 patients compared to patients with influenza infection, as well as in the lung tissue of K18-hACE2 Tg mice (Tg mice) infected with SARS-CoV-2. Genetic and pharmacological inhibition of C5aR1 signaling ameliorated lung immunopathology in Tg-infected mice. Mechanistically, we found that C5aR1 signaling drives neutrophil extracellular trap (NET)s-dependent immunopathology. These data confirm the immunopathological role of C5a/C5aR1 signaling in COVID-19 and indicate that antagonist of C5aR1 could be useful for COVID-19 treatment.

immunology↗

bioRxiv2022

A low-cost device for cryoanesthesia of neonate rodents

Studying the development of neural circuits in rodent models requires surgical access to the neonatal brain. Since commercially available stereotaxic and anesthetic equipment is designed for use in adults, reliable targeting of brain structures in such young animals can be challenging. Hypothermic cooling (cryoanesthesia) has been used as a preferred anesthesia approach in neonates. This commonly involves submerging neonates in ice, an approach that is poorly controllable. We have developed an affordable, simple to construct device - CryoPup - that allows for fast and robust cryoanesthesia of rodent pups. CryoPup consists of a microcontroller controlling a Peltier element and a heat exchanger. It is capable of both cooling and heating, thereby also functioning as a heating pad during recovery. Importantly, it has been designed for size compatibility with common stereotaxic frames. We validate CryoPup in neonatal mice, demonstrating that it allows for rapid, reliable and safe cryoanesthesia and subsequent recovery. This open-source device will facilitate future studies into the development of neural circuits in the postnatal brain. Specifications table O_TBL View this table: org.highwire.dtl.DTLVardef@de1fdorg.highwire.dtl.DTLVardef@16fde69org.highwire.dtl.DTLVardef@172f48corg.highwire.dtl.DTLVardef@15454forg.highwire.dtl.DTLVardef@79676e_HPS_FORMAT_FIGEXP M_TBL C_TBL

neuroscience↗

bioRxiv2020

Immunogenomic profile of colorectal cancer response to immune checkpoint blockade

Colorectal cancers (CRCs) show variable response to immune checkpoint blockade, which can only partially be explained by the variability of tumour mutational burden. To dissect the cellular and molecular determinants of response we performed a multi-omic screen of 721 cancer regions from patients treated with Pembrolizumab (KEYNOTE 177 clinical trial) or Nivolumab. Multi-regional whole exome, RNA and T-cell receptor sequencing show that, within hypermutated CRCs, response to both anti-PD1 agents is not positively associated with tumour mutational burden but with high clonality of immunogenic mutations, expanded T cells, low activation of the WNT pathway and active immune escape mechanisms. Coupling high-dimensional imaging mass cytometry with multiplexed immunofluorescence and computational spatial analysis, we observe that responsive hypermutated CRCs are rich in cytotoxic and proliferating PD1-expressing CD8 cells interacting with high-density clusters of PDL1-expressing antigen presenting macrophages. We propose that anti-PD1 agents release the PD1-PDL1 interaction between CD8 T cells and macrophages thus promoting cytotoxic anti-tumour activity.

cancer biology↗

bioRxiv2019

Perifornical Area Urocortin-3 Neurons Promote Infant-directed Neglect and Aggression

While recent studies have uncovered dedicated neural pathways mediating the positive control of parenting, the regulation of infant-directed aggression and how it relates to adult-adult aggression is poorly understood. Here we show that urocortin-3 (Ucn3)-expressing neurons in the hypothalamic perifornical area (PeFAUcn3) are activated during infant-directed attacks in males and females, but not other behaviors. Functional manipulations of PeFAUcn3 neurons demonstrate the role of this population in the negative control of parenting in both sexes. PeFAUcn3 neurons receive input from areas associated with vomeronasal sensing, stress, and parenting, and send projections to hypothalamic and limbic areas. Optogenetic activation of PeFAUcn3 axon terminals in these regions triggers various aspects of infant-directed agonistic responses, such as neglect, repulsion and aggression. Thus, PeFAUcn3 neurons emerge as a dedicated circuit component controlling infant-directed neglect and aggression, providing a new framework to understand the positive and negative regulation of parenting in health and disease.

neuroscience↗

bioRxiv2018

Functional and Anatomical Specificity in a Higher Olfactory Centre

Most sensory systems are organized into parallel neuronal pathways that process distinct aspects of incoming stimuli. For example, in insects, second order olfactory projection neurons target both the mushroom body, which is required for learning, and the lateral horn (LH), which has been proposed to mediate innate olfactory behavior. Mushroom body neurons encode odors in a sparse population code, which does not appear stereotyped across animals. In contrast the functional principles of odor coding in the LH remain poorly understood. We have carried out a comprehensive anatomical analysis of the Drosophila LH, counting ~1400 neurons; combining genetic driver lines, anatomical and functional criteria, we identify 165 LHN cell types. We then show that genetically labeled LHNs have stereotyped odor responses across animals for 33 of these cell types. LHN tuning can be ultra-sparse (1/40 odors tested), but on average single LHNs respond to three times more odors than single projection neurons. This difference can be rationalized by our observation that LHNs are better odor categorizers, likely due to pooling of input projection neurons responding to different odors of the same category. Our results reveal some of the principles by which a higher sensory processing area can extract innate behavioral significance from sensory stimuli.

neuroscience↗