The Role of TSC1 in the Formation and Maintenance of Excitatory Synapses
Abstract
Mutations In the TSC1 or TSC2 tumor suppressor genes lead to Tuberous Sclerosis Complex, a dominant disorder characterized by benign tumors in multiple organ systems. Patients with TSC also display neurological symptoms including epilepsy, autism, and mental retardation of unclear etiology. We induce loss of Tsc1 fraction of differentiated hippocampal pyramidal neurons and demonstrate that the TSC pathway cell-autonomously regulates neuronal structure and function. Loss of Tsc1 or Tsc2, including haploinsufficiency of Tsc1, leads to increases in soma size as well as enlargement and loss of dendritic spines. Functional analysis reveals these morphological changes are accompanied by perturbation of electrophysiological properties, including changes in strength and glutamate receptor composition of excitatory synapses. Our results reveal a role for the TSC pathway in the regulation of neuronal structure and function and suggest that cell-autonomous neuronal defects contribute to the pathogenesis of the neurological symptoms of TSC.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2005
- Accession Number
- ADA437200
Entities
People
- Bernardo L. Sabatini
Organizations
- Harvard Medical School