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Biology subjects

Garthe, A.

Publications and source records attributed to Garthe, A..

3 recordsLinked to original sources

Co-option of CENP-A for activity-induced neuronal plasticity

Neuronal activation drives activity-dependent gene expression that underlies experience-associated synaptic modifications, learning and memory. Here we show that the histone variant CENP-A, best known for specifying centromere identity, is dynamically regulated by synaptic activity at both the RNA and protein levels in postmitotic neurons. Neuronal activation increases a non-centromeric nuclear pool of CENP-A while leaving centromeric CENP-A levels unchanged. Downregulation of CENP-A selectively reduces the activity-associated non-centromeric pool, impairs activity-dependent induction of immediate-early genes such as FOS and ARC, and disrupts hippocampus-dependent learning and memory. Furthermore, we find that activity-dependent neuronal responses in human embryonic stem cell-derived forebrain organoids similarly require CENP-A. Our results reveal a mitosis-independent, conserved role of CENP-A for driving plasticity in mammalian neurons.

neuroscience↗

Adult-born neurons promote cognitive flexibility by improving memory precision and indexing

The dentate gyrus (DG) of the hippocampus is fundamental for cognitive flexibility and has the extraordinary ability to generate new neurons throughout life. Recent evidence suggested that adult-born neurons differentially modulate input to the DG during the processing of spatial information and novelty. However, how this differential regulation by neurogenesis is translated into different aspects contributing cognitive flexibility is unclear. Here, we increased adult-born neurons by a genetic expansion of neural stem cells and studied their influence during navigational learning. We found that increased neurogenesis improved memory precision, indexing and retention and that each of these gains was associated with a differential activation of specific DG compartments and better separation of memory representations in the DG-CA3 network. Our results highlight the role of adult-born neurons in promoting memory precision in the infrapyramidal and indexing in the suprapyramidal blade of the DG and together contributing to cognitive flexibility. One sentence summaryNeurogenesis improves memory precision and indexing.

neuroscience↗

Rtrack: a software package for reproducible automated water maze analysis

Rtrack is an open-source software package for the analysis of spatial exploration data from behavioural tests such as the Morris water maze. The software provides an easy-to-use interface for data import, analysis and visualisation. A parameter-free machine learning model allows rapid and reproducible classification of spatial search strategies. We also propose a standard export format to enable cross-platform data sharing for the first time in the field.

animal behavior and cognition↗