October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Clinical Center Tours
- Research Festival Committees
- Past Research Festivals
Mechanisms of glutamate transporter trafficking in response to amphetamine
| Wednesday, November 06, 2013 — Poster Session I | |||
|---|---|---|---|
4:00 p.m. – 6:00 p.m. |
FAES Academic Center (Upper-Level Terrace) |
NIMH |
NEURO-38 |
Authors
- S.M. Underhill
- S.G. Amara
Abstract
Amphetamine (AMPH) affects brain activity largely through modifications of the dopamine system; however, there is also a change in levels of extracellular glutamate accompanying AMPH administration. This elevation in extracellular glutamate may be due to increased glutamatergic synaptic activity as well as changes in the efficiency of glutamate buffering and clearance. The excitatory amino acid transporters, EAATs, are responsible for clearing extracellular glutamate and we hypothesized that trafficking of the carrier contributes to AMPH-induced increases in extracellular glutamate. We found that the neuronal glutamate transporter, EAAT3, was selectively sensitive to AMPH. In several model systems, EAAT3 was internalized in response to AMPH. This trafficking was dynamin-dependent and clathrin-independent. Activation of the small GTPase Rho was necessary for EAAT3 internalization as was subsequent activation of the Rho-Kinase. We also identified a cytosolic domain on the EAAT3 that conveys sensitivity to AMPH. Blocking interaction with this domain through mutation or with a small interfering peptide prevented AMPH-mediated EAAT3 internalization. These data indicate a novel mechanism by which AMPH affects glutamate concentrations in the brain.
