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Biology subjects

Lundt, F.

Publications and source records attributed to Lundt, F..

2 recordsLinked to original sources

Memory consolidation and representational drift

Memory consolidation is the process by which temporary, malleable memories are transformed into more stable, longer-lasting forms. On a coarse anatomical scale, consolidation redistributes memories in the brain, but it remains poorly understood how these changes manifest themselves on the finer, cellular scale of neuronal engrams and how they relate to the cognitive level. In this study, we developed a phenomenological model of engram dynamics under systems consolidation. The model describes consolidation as a brain-wide phenomenon, where memories deterministically follow a trajectory through a space of patterns distributed among brain regions. It captures a broad range of features of memory consolidation, including selective consolidation, semantization, and power-law forgetting. In the model, consolidation is accompanied by population-level changes in neuronal representations that resemble the widely observed phenomenon of representational drift. When only a subset of neurons is observed, the deterministic dynamics of the model can appear stochastic, and a readout of task features deteriorates over time even when a stable readout exists for the full system. Our model offers a dynamical systems perspective on memory consolidation as a distributed process, moving beyond the classic region-centered view, and provides a functional interpretation of drift as a means of redistributing engrams for improved memory retention.

neuroscience↗

Endocardial primary cilia and blood flow are required for regulation of EndoMT during endocardial cushion development

Blood flow is critical for heart valve formation, and cellular mechanosensors are essential to translate flow into transcriptional regulation of development. Here, we identify a role for primary cilia in vivo in the spatial regulation of cushion formation, the first stage of valve development, by regionally controlling endothelial to mesenchymal transition (EndoMT) via modulation of Kruppel-like Factor 4 (Klf4). We find that high shear stress intracardiac regions decrease endocardial ciliation over cushion development, correlating with KLF4 downregulation and EndoMT progression. Mouse embryos constitutively lacking cilia exhibit a blood-flow dependent accumulation of KLF4 in these regions, independent of upstream left-right abnormalities, resulting in impaired cushion cellularization. snRNA-seq revealed that cilia KO endocardium fails to progress to late-EndoMT, retains endothelial markers and has reduced EndoMT/mesenchymal genes that KLF4 antagonizes. Together, these data identify a mechanosensory role for endocardial primary cilia in cushion development through regional regulation of KLF4.

developmental biology↗