scholarly journals Altered A-type potassium channel function impairs dendritic spike initiation and temporoammonic long-term potentiation in Fragile X syndrome

2021 ◽  
pp. JN-RM-0082-21
Author(s):  
Gregory J. Ordemann ◽  
Christopher J. Apgar ◽  
Raymond A. Chitwood ◽  
Darrin H. Brager
Keyword(s):  
Potassium Channel ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Long Term Potentiation ◽  
Channel Function ◽  
Term Potentiation ◽  
Dendritic Spike ◽  
Spike Initiation

scholarly journals Altered A-type potassium channel function impairs dendritic spike initiation and temporammonic long-term potentiation in Fragile X syndrome

2021 ◽  
Author(s):  
Gregory J. Ordemann ◽  
Christopher J. Apgar ◽  
Raymond A. Chitwood ◽  
Darrin H Brager
Keyword(s):  
Fragile X Syndrome ◽  
Fragile X ◽  
Long Term Potentiation ◽  
Autism Spectrum ◽  
K Channels ◽  
Spike Threshold ◽  
Type K ◽  
Term Potentiation ◽  
Dendritic Spike

Fragile X syndrome (FXS) is the leading monogenetic cause of cognitive impairment and autism spectrum disorder. Area CA1 of the hippocampus receives current information about the external world from the entorhinal cortex via the temporoammonic (TA) pathway. Given its role in learning and memory, it is surprising that little is known about TA long-term potentiation (TA-LTP) in FXS. We found that TA-LTP was impaired in fmr1 KO mice. Furthermore, dendritic Ca2+ influx was smaller and dendritic spike threshold was depolarized in fmr1 KO mice. Dendritic spike threshold and TA-LTP were restored by block of A-type K+ channels. The impairment of TA-LTP coupled with enhanced Schaffer collateral LTP may contribute to spatial memory alterations in FXS. Furthermore, as both of these LTP phenotypes are attributed to changes in A-type K+ channels in FXS, our findings provide a potential therapeutic target to treat cognitive impairments in FXS.

scholarly journals Age-Dependent Long-Term Potentiation Deficits in the Prefrontal Cortex of theFmr1Knockout Mouse Model of Fragile X Syndrome

2015 ◽  
Vol 26 (5) ◽  
pp. 2084-2092 ◽  
Author(s):  
Henry G. S. Martin ◽  
Olivier Lassalle ◽  
Jonathan T. Brown ◽  
Olivier J. Manzoni
Keyword(s):  
Prefrontal Cortex ◽  
Mouse Model ◽  
Fragile X Syndrome ◽  
Fragile X ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
Age Dependent

Long-term potentiation in the hippocampus of fragile X knockout mice

1996 ◽  
Vol 64 (2) ◽  
pp. 246-251 ◽  
Author(s):  
Jean-Marie Godfraind ◽  
Edwin Reyniers ◽  
Kristel De Boulle ◽  
Rudi D'Hooge ◽  
Peter P. De Deyn ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Fragile X ◽  
Long Term Potentiation ◽  
Term Potentiation

scholarly journals Glycogen Synthase Kinase-3 Inhibitors Reverse Deficits in Long-term Potentiation and Cognition in Fragile X Mice

2014 ◽  
Vol 75 (3) ◽  
pp. 198-206 ◽  
Author(s):  
Aimee V. Franklin ◽  
Margaret K. King ◽  
Valle Palomo ◽  
Ana Martinez ◽  
Lori L. McMahon ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Fragile X ◽  
Long Term Potentiation ◽  
Glycogen Synthase Kinase ◽  
Glycogen Synthase Kinase 3 ◽  
Term Potentiation

scholarly journals Early Postnatal Plasticity in Neocortex of Fmr1 Knockout Mice

2006 ◽  
Vol 96 (4) ◽  
pp. 1734-1745 ◽  
Author(s):  
Niraj S. Desai ◽  
Tanya M. Casimiro ◽  
Stephen M. Gruber ◽  
Peter W. Vanderklish
Keyword(s):  
Knockout Mice ◽  
Developmental Plasticity ◽  
Fragile X ◽  
Long Term Potentiation ◽  
Receptor Activation ◽  
Spike Timing ◽  
Term Potentiation ◽  
Spine Abnormalities ◽  
Intrinsic Plasticity

Fragile X syndrome is produced by a defect in a single X-linked gene, called Fmr1, and is characterized by abnormal dendritic spine morphologies with spines that are longer and thinner in neocortex than those from age-matched controls. Studies using Fmr1 knockout mice indicate that spine abnormalities are especially pronounced in the first month of life, suggesting that altered developmental plasticity underlies some of the behavioral phenotypes associated with the syndrome. To address this issue, we used intracellular recordings in neocortical slices from early postnatal mice to examine the effects of Fmr1 disruption on two forms of plasticity active during development. One of these, long-term potentiation of intrinsic excitability, is intrinsic in expression and requires mGluR5 activation. The other, spike timing-dependent plasticity, is synaptic in expression and requires N-methyl-d-aspartate receptor activation. While intrinsic plasticity was normal in the knockout mice, synaptic plasticity was altered in an unusual and striking way: long-term depression was robust but long-term potentiation was entirely absent. These findings underscore the ideas that Fmr1 has highly selective effects on plasticity and that abnormal postnatal development is an important component of the disorder.

Sign in / Sign up

Export Citation Format

Share Document