Variability of axon initial segment geometry and its impact on hippocampal pyramidal cell function DOI Creative Commons
Nikolas A Stevens,

Maximilian Achilles,

Juri Monath

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

ABSTRACT Action potentials, the primary information units of nervous system, are usually generated at axon initial segment (AIS). Changes in length and position AIS associated with alterations neuronal excitability but there is only limited about baseline structural variability AIS. This work provides a comprehensive atlas diversity proximal cell geometries across all anatomical axes murine hippocampus, encompassing dorsal-ventral, superficial-deep, proximal-distal regions. We analyzed morphology 3,936 hippocampal pyramidal neurons 12 animals both sexes, focusing on length, position, their association cellular features such as soma dendritic geometries. Notably, axon-carrying dendrites were significantly more common ventral compared to dorsal areas, suggesting functional adaptation regional demands. Validation this finding human samples confirms translational relevance our model. employed NEURON simulations assess implications variability. Here, variation geometry minimally contributed homeostasis, instead increased heterogeneity response patterns neurons.

Language: Английский

Efficient axonal transport of endolysosomes relies on the balanced ratio of microtubule tyrosination and detyrosination DOI Creative Commons
Anja Konietzny, Yuhao Han, Yannes Popp

et al.

Journal of Cell Science, Journal Year: 2024, Volume and Issue: 137(8)

Published: March 25, 2024

ABSTRACT In neurons, the microtubule (MT) cytoskeleton forms basis for long-distance protein transport from cell body into and out of dendrites axons. To maintain neuronal polarity, axon initial segment (AIS) serves as a physical barrier, separating somatodendritic compartment acting filter axonal cargo. Selective trafficking is further instructed by enrichment MT post-translational modifications, which affect dynamics activity motor proteins. Here, we compared two knockout mouse lines lacking respective enzymes tyrosination detyrosination, found that both knockouts led to shortening AIS. Neurons also showed an increased immobile fraction endolysosomes present in axon, whereas mobile organelles displayed shortened run distances retrograde direction. Overall, our results highlight importance maintaining balance tyrosinated detyrosinated MTs proper AIS length processes.

Language: Английский

Citations

4
Variability of axon initial segment geometry and its impact on hippocampal pyramidal cell function DOI Creative Commons
Nikolas A Stevens,

Maximilian Achilles,

Juri Monath

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

ABSTRACT Action potentials, the primary information units of nervous system, are usually generated at axon initial segment (AIS). Changes in length and position AIS associated with alterations neuronal excitability but there is only limited about baseline structural variability AIS. This work provides a comprehensive atlas diversity proximal cell geometries across all anatomical axes murine hippocampus, encompassing dorsal-ventral, superficial-deep, proximal-distal regions. We analyzed morphology 3,936 hippocampal pyramidal neurons 12 animals both sexes, focusing on length, position, their association cellular features such as soma dendritic geometries. Notably, axon-carrying dendrites were significantly more common ventral compared to dorsal areas, suggesting functional adaptation regional demands. Validation this finding human samples confirms translational relevance our model. employed NEURON simulations assess implications variability. Here, variation geometry minimally contributed homeostasis, instead increased heterogeneity response patterns neurons.

Language: Английский

Citations

0