Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of function of the maternal UBE3A gene. The hippocampus is one of the most prominently affected brain regions in AS model mice, manifesting in severe hippocampal-dependent memory and plasticity deficits. Previous studies in AS mice reported an elongated axon initial segment (AIS) in pyramidal neurons (PNs) of the hippocampal CA1 region. These were the first reports in mammals to show AIS elongation in vivo. Correspondingly, this AIS elongation was linked to enhanced expression of the α1 subunit of Na+/K+-ATPase (α1-NaKA). Recently, it was shown that selective pharmacological inhibition of α1-NaKA by marinobufagenin (MBG) in adult AS mice rescued the hippocampal-dependent deficits via normalizing their compromised activity-dependent calcium (Ca+2) dynamics. In the herein study, we showed that a chronic selective α1-NaKA inhibition reversed the AIS elongation in hippocampal CA1 PNs of adult AS mice, and differentially altered their excitability and intrinsic properties. Taken together, our study is the first to demonstrate in vivo structural plasticity of the AIS in a mammalian model, and further elaborates on the modulatory effects of elevated α1-NaKA levels in the hippocampus of AS mice.
Bibliographical noteFunding Information:
This work was supported by the Israel Science Foundation (grant number 248/20) and by the Angelman syndrome foundation (ASF). The authors declare no competing interests.
© 2020, The Author(s), under exclusive licence to American College of Neuropsychopharmacology.
- Adenosine Triphosphatases
- Angelman syndrome
- Axon Initial Segment
- CA1 Region, Hippocampal
- Pyramidal Cells
ASJC Scopus subject areas
- Psychiatry and Mental health