PTEN knockdown alters dendritic spine/protrusion morphology, not density
Michael E Haws1, Thomas C Jaramillo, Felipe Espinosa
1Department of Neurology & Neurotherapeutics, The University of Texas Southwestern Medical Center, Dallas, Texas, 75390-8813; Neuroscience Graduate Program, The University of Texas Southwestern Medical Center, Dallas, Texas, 75390-8813.
The Journal of Comparative Neurology
|November 23, 2013
Summary
Loss of PTEN in amygdala neurons decreases total spine density but increases mature mushroom spine function, suggesting synaptic maturation rather than new spine growth. This may not cause anxiety-related behaviors.
Area of Science:
- Neuroscience
- Molecular Biology
- Synaptic Plasticity
Background:
- Mutations in Phosphatase and Tensin Homolog deleted on chromosome 10 (PTEN) are linked to neuropsychiatric disorders.
- Previous research indicated PTEN knockdown increases neuronal spine density and synaptic activity.
Purpose of the Study:
- To investigate the effects of PTEN knockdown on synaptic structure and function in basolateral amygdala (BLA) neurons.
- To reconcile conflicting findings regarding PTEN's role in spinogenesis and synaptic activity.
Main Methods:
- Utilized shRNA to knock down PTEN in BLA neurons.
- Employed fluorescent dye confocal imaging to analyze dendritic spine density and morphology.
- Conducted electrophysiological recordings to measure miniature excitatory postsynaptic current (mEPSC) frequency and amplitude.
- Performed behavioral analyses to assess anxiety-related behaviors.
Main Results:
- PTEN knockdown in BLA neurons significantly decreased total dendritic spine density but increased mEPSC frequency and amplitude.
- Spine morphology analysis revealed an increase in mushroom spine density and size, with a decrease in thin protrusion density.
- Loss of PTEN in the dentate gyrus decreased thin protrusions and increased mature mushroom spines, without altering total dendritic protrusions.
- BLA-specific PTEN knockdown did not induce increased anxiety-related behaviors.
Conclusions:
- PTEN knockdown promotes synaptic maturation, increasing the number and function of mature spines, rather than inducing de novo spinogenesis.
- Synaptic changes in the BLA due to PTEN loss may not be sufficient to alter anxiety-related behaviors.
- PTEN plays a critical role in regulating spine morphology and synaptic function, with region-specific effects.
