title: PTEN knockdown alters dendritic spine/protrusion morphology, not density.
abstract: Mutations in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) are implicated in neuropsychiatric disorders including autism. Previous studies report that PTEN knockdown in neurons in vivo leads to increased spine density and synaptic activity. To better characterize synaptic changes in neurons lacking PTEN, we examined the effects of shRNA knockdown of PTEN in basolateral amygdala neurons on synaptic spine density and morphology by using fluorescent dye confocal imaging. Contrary to previous studies in the dentate gyrus, we find that knockdown of PTEN in basolateral amygdala leads to a significant decrease in total spine density in distal dendrites. Curiously, this decreased spine density is associated with increased miniature excitatory postsynaptic current frequency and amplitude, suggesting an increase in number and function of mature spines. These seemingly contradictory findings were reconciled by spine morphology analysis demonstrating increased mushroom spine density and size with correspondingly decreased thin protrusion density at more distal segments. The same analysis of PTEN conditional deletion in the dentate gyrus demonstrated that loss of PTEN does not significantly alter total density of dendritic protrusions in the dentate gyrus, but does decrease thin protrusion density and increases density of more mature mushroom spines. These findings suggest that, contrary to previous reports, PTEN knockdown may not induce de novo spinogenesis, but instead may increase synaptic activity by inducing morphological and functional maturation of spines. Furthermore, behavioral analysis of basolateral amygdala PTEN knockdown suggests that these changes limited only to the basolateral amygdala complex may not be sufficient to induce increased anxiety-related behaviors.
authors.affiliation: Department 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.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Haws
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Jaramillo
authors.forename: Felipe
authors.initials: F
authors.lastname: Espinosa
authors.forename: Allie J
authors.initials: AJ
authors.lastname: Widman
authors.forename: Garret D
authors.initials: GD
authors.lastname: Stuber
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Sparta
authors.forename: Kay M
authors.initials: KM
authors.lastname: Tye
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Russo
authors.forename: Luis F
authors.initials: LF
authors.lastname: Parada
authors.forename: Mihaela
authors.initials: M
authors.lastname: Stavarache
authors.forename: Michael
authors.initials: M
authors.lastname: Kaplitt
authors.forename: Antonello
authors.initials: A
authors.lastname: Bonci
authors.forename: Craig M
authors.initials: CM
authors.lastname: Powell
mesh_terms: D000679:Amygdala / Q000166:cytology*; D000818:Animals; D001007:Anxiety / Q000235:genetics; D001522:Behavior, Animal / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology; D049229:Dendritic Spines / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D008124:Locomotion / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D055369:Miniature Postsynaptic Potentials / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D009474:Neurons / Q000648:ultrastructure*; D051058:Oncogene Protein v-akt / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D013216:Reflex, Startle / Q000235:genetics; D014161:Transduction, Genetic
chemical_list: D049452:Green Fluorescent Proteins; D051058:Oncogene Protein v-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D010751:Phosphopyruvate Hydratase
keywords: AKT; PTEN; amygdale; dendrite; dentate gyrus; mTOR; spine