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 ASD-like 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.
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| http://dx.doi.org/10.1016/j.neuron.2014.07.040 | DOI Listing |
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Article Synopsis
- Developmental plasticity is key to understanding how the brain adapts and changes structure during learning, but current neural network compression methods inadequately mimic these biological processes.
- A new method called developmental plasticity-inspired adaptive pruning (DPAP) is introduced, which mimics biological pruning mechanisms in the brain and optimizes network structure dynamically during learning.
- Experiments demonstrate that the DPAP approach significantly enhances performance and speed in compressed deep artificial neural networks and spiking neural networks, achieving state-of-the-art results in certain tasks.
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