Journal
NEURON
Volume 83, Issue 5, Pages 1131-1143Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2014.07.040
Keywords
-
Categories
Funding
- Simons Foundation
- DOD TSCRP [TS110056]
- Parkinson's Disease Foundation from NIMH [K01MH096956]
- JPB Foundation from NIMH [K01MH096956]
- AHA
- NIMH [MH64168]
- NIH [DP2OD001674-01, NS049442]
Ask authors/readers for more resources
Developmental alterations of excitatory synapses are implicated in autism spectrum disorders (ASDs). Here, we report increased dendritic spine density with reduced developmental spine pruning in layer V pyramidal neurons in postmortem ASD temporal lobe. These spine deficits correlate with hyperactivated mTOR and impaired autophagy. In Tsc2+/- ASD mice where mTOR is constitutively overactive, we observed postnatal spine pruning defects, blockade of autophagy, and ASD-like social behaviors. The mTOR inhibitor rapamycin corrected ASDlike behaviors and spine pruning defects in Tsc2+/ mice, but not in Atg7(CKO) neuronal autophagy-deficient mice or Tsc2+/- : Atg7(CKO) double mutants. Neuronal autophagy furthermore enabled spine elimination with no effects on spine formation. Our findings suggest that mTOR-regulated autophagy is required for developmental spine pruning, and activation of neuronal autophagy corrects synaptic pathology and social behavior deficits in ASD models with hyperactivated mTOR.
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