Cortical synaptic and dendritic spine abnormalities in a presymptomatic TDP-43 model of amyotrophic lateral sclerosis

Fogarty, Matthew J., Klenowski, Paul M., Lee, John D., Drieberg-Thompson, Joy R., Bartlett, Selena E., Ngo, Shyuan T., Hilliard, Massimo A., Bellingham, Mark C. and Noakes, Peter G. (2016) Cortical synaptic and dendritic spine abnormalities in a presymptomatic TDP-43 model of amyotrophic lateral sclerosis. Scientific Reports, 6 . doi:10.1038/srep37968


Author Fogarty, Matthew J.
Klenowski, Paul M.
Lee, John D.
Drieberg-Thompson, Joy R.
Bartlett, Selena E.
Ngo, Shyuan T.
Hilliard, Massimo A.
Bellingham, Mark C.
Noakes, Peter G.
Title Cortical synaptic and dendritic spine abnormalities in a presymptomatic TDP-43 model of amyotrophic lateral sclerosis
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2016-11-29
Sub-type Article (original research)
DOI 10.1038/srep37968
Open Access Status Not yet assessed
Volume 6
Total pages 13
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Collection year 2017
Language eng
Abstract Layer V pyramidal neurons (LVPNs) within the motor cortex integrate sensory cues and co-ordinate voluntary control of motor output. In amyotrophic lateral sclerosis (ALS) LVPNs and spinal motor neurons degenerate. The pathogenesis of neural degeneration is unknown in ALS; 10% of cases have a genetic cause, whereas 90% are sporadic, with most of the latter showing TDP-43 inclusions. Clinical and experimental evidence implicate excitotoxicity as a prime aetiological candidate. Using patch clamp and dye-filling techniques in brain slices, combined with high-resolution confocal microscopy, we report increased excitatory synaptic inputs and dendritic spine densities in early presymptomatic mice carrying a TDP-43 Q331K mutation. These findings demonstrate substantive alterations in the motor cortex neural network, long before an overt degenerative phenotype has been reported. We conclude that increased excitatory neurotransmission is a common pathophysiology amongst differing genetic cases of ALS and may be of relevance to the 95% of sporadic ALS cases that exhibit TDP-43 inclusions.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

 
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