Abstract
Amphetamines modify the brain and alter behavior through mechanisms generally attributed to their ability to regulate extracellular dopamine concentrations. However, the actions of amphetamine are also linked to adaptations in glutamatergic signaling. We report here that when amphetamine enters dopamine neurons through the dopamine transporter, it stimulates endocytosis of an excitatory amino acid transporter, EAAT3, in dopamine neurons. Consistent with this decrease in surface EAAT3, amphetamine potentiates excitatory synaptic responses in dopamine neurons. We also show that the process of internalization is dynamin- and Rho-mediated and requires a unique sequence in the cytosolic C terminus of EAAT3. Introduction of a peptide based on this motif into dopamine neurons blocks the effects of amphetamine on EAAT3 internalization andits action on excitatory responses. These data indicate that the internalization of EAAT3 triggered byamphetamine increases glutamatergic signaling and thus contributes to the effects of amphetamine on neurotransmission.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 404-416 |
| Number of pages | 13 |
| Journal | Neuron |
| Volume | 83 |
| Issue number | 2 |
| DOIs | |
| State | Published - Jul 16 2014 |
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ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Amphetamine Modulates Excitatory Neurotransmission through Endocytosis of the Glutamate Transporter EAAT3 in Dopamine Neurons. / Underhill, Suzanne M.; Wheeler, David S.; Li, Minghua; Watts, Spencer D.; Ingram, Susan; Amara, Susan G.
In: Neuron, Vol. 83, No. 2, 16.07.2014, p. 404-416.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Amphetamine Modulates Excitatory Neurotransmission through Endocytosis of the Glutamate Transporter EAAT3 in Dopamine Neurons
AU - Underhill, Suzanne M.
AU - Wheeler, David S.
AU - Li, Minghua
AU - Watts, Spencer D.
AU - Ingram, Susan
AU - Amara, Susan G.
PY - 2014/7/16
Y1 - 2014/7/16
N2 - Amphetamines modify the brain and alter behavior through mechanisms generally attributed to their ability to regulate extracellular dopamine concentrations. However, the actions of amphetamine are also linked to adaptations in glutamatergic signaling. We report here that when amphetamine enters dopamine neurons through the dopamine transporter, it stimulates endocytosis of an excitatory amino acid transporter, EAAT3, in dopamine neurons. Consistent with this decrease in surface EAAT3, amphetamine potentiates excitatory synaptic responses in dopamine neurons. We also show that the process of internalization is dynamin- and Rho-mediated and requires a unique sequence in the cytosolic C terminus of EAAT3. Introduction of a peptide based on this motif into dopamine neurons blocks the effects of amphetamine on EAAT3 internalization andits action on excitatory responses. These data indicate that the internalization of EAAT3 triggered byamphetamine increases glutamatergic signaling and thus contributes to the effects of amphetamine on neurotransmission.
AB - Amphetamines modify the brain and alter behavior through mechanisms generally attributed to their ability to regulate extracellular dopamine concentrations. However, the actions of amphetamine are also linked to adaptations in glutamatergic signaling. We report here that when amphetamine enters dopamine neurons through the dopamine transporter, it stimulates endocytosis of an excitatory amino acid transporter, EAAT3, in dopamine neurons. Consistent with this decrease in surface EAAT3, amphetamine potentiates excitatory synaptic responses in dopamine neurons. We also show that the process of internalization is dynamin- and Rho-mediated and requires a unique sequence in the cytosolic C terminus of EAAT3. Introduction of a peptide based on this motif into dopamine neurons blocks the effects of amphetamine on EAAT3 internalization andits action on excitatory responses. These data indicate that the internalization of EAAT3 triggered byamphetamine increases glutamatergic signaling and thus contributes to the effects of amphetamine on neurotransmission.
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UR - http://www.scopus.com/inward/citedby.url?scp=84904315691&partnerID=8YFLogxK
U2 - 10.1016/j.neuron.2014.05.043
DO - 10.1016/j.neuron.2014.05.043
M3 - Article
VL - 83
SP - 404
EP - 416
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 2
ER -