Biology subjects

van Dijk, M.

Publications and source records attributed to van Dijk, M..

4 recordsLinked to original sources

bioRxiv2025

Sociability is a multidimensional trait in Drosophila melanogaster

Sociability--the propensity of an individual to engage in group activities--is a trait present in all social species. In humans and many animals, sociability varies between individuals yet remains consistent across contexts, qualifying it as a personality trait. Sociability influences health and physiology, but the mechanisms underlying sociability and its inter-individual variation remain poorly understood. The genetically tractable fruit fly, Drosophila melanogaster, is increasingly used to study social behavior and exhibits a wide range of sociability phenotypes. However, previous studies have relied on distinct behavioral paradigms, limiting cross-context comparisons and motivating a more extensive characterization of sociability in this species. Here, we quantified sociability in D. melanogaster using a multidimensional approach encompassing three paradigms that capture engagement in group activities across contexts: (1) preference for communal versus solitary egg-laying, (2) egg-laying latency in a group, and (3) frequency and duration of spontaneous social interactions and interindividual distance. We assessed these behaviors in 105 lines of the Drosophila Genetic Reference Panel and observed substantial variation in responses to conspecific presence across paradigms. Sociability-related behaviors differed between genetically distinct lines, indicating a genetic component. However, the three sociability traits were uncorrelated, demonstrating that sociability in D. melanogaster is multidimensional. These findings suggest that sociability is not governed by a single central mechanism, but instead arises from multiple context-dependent pathways.

animal behavior and cognition↗

bioRxiv2022

Phencyclidine disrupts neural coordination and cognitive control by dysregulating translation

BackgroundPhencyclidine (PCP) causes psychosis, is abused with increasing frequency, and was extensively used in antipsychotic drug discovery. PCP discoordinates hippocampal ensemble action potential discharge and impairs cognitive control in rats, but how this uncompetitive N-methyl-D-aspartate receptor (NMDAR) antagonist impairs cognition remains unknown. MethodsThe effects of PCP were investigated i) on hippocampal CA1 ensemble action potential discharge in vivo in urethane-anesthetized rats and during awake behavior in mice; ii) on synaptic responses in ex vivo mouse hippocampus slices; iii) in mice on a hippocampus-dependent active place avoidance task that requires cognitive control; and iv) on activating the molecular machinery of translation in acute hippocampus slices. Mechanistic causality was assessed by comparing the PCP effects to the effects of inhibitors of protein synthesis, group-1-type metabotropic glutamate receptors (mGluR1/5), and subunit-selective NMDARs. ResultsConsistent with ionotropic actions, PCP discoordinated CA1 ensemble action potential discharge. PCP caused hyperactivity, and impaired active place avoidance, despite learning the task before PCP. Consistent with metabotropic actions, PCP exaggerated protein-synthesis dependent DHPG-induced mGluR1/5-stimulated long-term synaptic depression (LTD). Pretreatment with anisomycin or the mGluR1/5-antagonist MPEP, both of which repress translation, prevented the PCP-induced discoordination, and the cognitive and sensorimotor impairments. PCP as well as the NR2A-containing NMDAR-antagonist NVP-AAM077 unbalanced translation that engages the AKT, mTOR and 4EBP1 translation machinery and increased protein synthesis, whereas the NR2B-containing antagonist Ro25-6981 did not. ConclusionsPCP dysregulates translation, acting through NR2A-containing NMDAR subtypes, recruiting mGluR1/5 signaling pathways, leading to the neural discoordination that is central to the cognitive and sensorimotor impairments.

neuroscience↗

bioRxiv2020

Breast cancer dormancy is associated with a 4NG1 state and not senescence

Reactivation of dormant cancer cells can lead to cancer relapse, metastasis and patient death. Dormancy is a non-proliferative state and is linked to late relapse and death. No targeted therapy is currently available to eliminate dormant cells, highlighting the need for a deeper understanding and reliable models. Here, we thoroughly characterize the dormant D2.OR and proliferative D2A1 breast cancer cell line models in vivo and in vitro, and assess if there is overlap between a dormant and a senescent phenotype. We show that D2.OR but not D2A1 cells become dormant in the liver of an immunocompetent model. In vitro, we show that D2.OR cells are polyploid ER+/Her2+ cells, and in response to a 3D environment are growth arrested in G1, of which a subpopulation resides in a 4NG1 state. The dormancy state is reversible, and not associated with a senescence phenotype. This will aid future research on breast cancer dormancy.

cell biology↗

bioRxiv2017

On how the dentate gyrus contributes to memory discrimination

SummaryThe dentate gyrus (DG) is crucial for behaviorally discriminating similar spatial memories, predicting that dentate gyrus place cells change (\"remap\") spatial tuning (\"place fields\") for memory discrimination. This prediction was never tested, although DG place cells remap across similar environments without memory tasks. We confirm this prior finding, then demonstrate that DG place fields do not remap across spatial tasks that require DG-dependent memory discrimination. Instead of remapping, place-discriminating discharge is observed transiently amongst DG place cells, particularly where memory discrimination is most necessary. The DG network signals memory discrimination by expressing distinctive sub-second network patterns of co-firing amongst principal cells at memory discrimination sites. This is accompanied by increased coupling of discharge from excitatory principal cells and inhibitory interneurons. Instead of remapping, these findings identify that memory discrimination is signaled by sub-second patterns of correlated discharge within the dentate network.\n\neTOC blurbvan Dijk and Fenton report that dentate gyrus place cells signal memory discrimination not by remapping, but by variable sub-second patterns of coordinated place cell network discharge and enhanced discharge coupling between excitatory and inhibitory neurons, at sites of memory discrimination.\n\nHighlightsO_LIDentate gyrus-dependent memory discrimination does not require place cell remapping\nC_LIO_LIDentate neural correlates of pattern discrimination are transient, lasting seconds\nC_LIO_LISub-second dentate network discharge correlations signal memory discrimination\nC_LIO_LIDentate excitatory-inhibitory coupling is increased at memory discrimination sites\nC_LI

neuroscience↗