Journal
CELL REPORTS
Volume 32, Issue 6, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.107988
Keywords
-
Categories
Funding
- Simons Foundation Autism Research Initiative [529085]
- Patrick Wild Centre
- Medical Research Council UK [MR/P006213/1]
- Shirley Foundation
- R S Macdonald Charitable Trust
- MRC [MR/P006213/1, UKDRI-4001] Funding Source: UKRI
Ask authors/readers for more resources
Cellular hyperexcitability is a salient feature of fragile X syndrome animal models. The cellular basis of hyperexcitability and how it responds to changing activity states is not fully understood. Here, we show increased axon initial segment length in CA1 of the Fmr1(-/y) mouse hippocampus, with increased cellular excitability. This change in length does not result from reduced AIS plasticity, as prolonged depolarization induces changes in AIS length independent of genotype. However, depolarization does reduce cellular excitability, the magnitude of which is greater in Fmr1(-/y) neurons. Finally, we observe reduced functional inputs from the entorhinal cortex, with no genotypic difference in the firing rates of CA1 pyramidal neurons. This suggests that AIS-dependent hyperexcitability in Fmr1(-/y) mice may result from adaptive or homeostatic regulation induced by reduced functional synaptic connectivity. Thus, while AIS length and intrinsic excitability contribute to cellular hyperexcitability, they may reflect a homeostatic mechanism for reduced synaptic input onto CA1 neurons.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available