Neuronal glutamate transporters regulate glial excitatory transmission.
In the CNS, excitatory amino acid transporters (EAATs) localized to neurons and glia terminate the actions of synaptically released glutamate. Whereas glial transporters are primarily responsible for maintaining low ambient levels of extracellular glutamate, neuronal transporters have additional roles in shaping excitatory synaptic transmission. Here we test the hypothesis that the expression level of the Purkinje cell (PC)-specific transporter, EAAT4, near parallel fiber (PF) release sites controls the extrasynaptic glutamate concentration transient following synaptic stimulation. Expression of EAAT4 follows a parasagittal banding pattern that allows us to compare regions of high and low EAAT4-expressing PCs. Using EAAT4 promoter-driven eGFP reporter mice together with pharmacology and genetic deletion, we show that the level of neuronal transporter expression influences extrasynaptic transmission from PFs to adjacent Bergmann glia (BG). Surprisingly, a twofold difference in functional EAAT4 levels is sufficient to alter signaling to BG, although EAAT4 may only be responsible for removing a fraction of released glutamate. These results demonstrate that physiological regulation of neuronal transporter expression can alter extrasynaptic neuroglial signaling.
Department of Neurobiology and Evelyn McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Ming-Chi
MC
Tsai
Kohichi
K
Tanaka
Linda
L
Overstreet-Wadiche
Jacques I
JI
Wadiche
D027322:Amino Acid Transport System X-AG / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000187:drug effects / Q000502:physiology; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D050581:Excitatory Amino Acid Transporter 4 / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009924:Organ Culture Techniques; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D027322:Amino Acid Transport System X-AG; D018683:Excitatory Amino Acid Agents; D050581:Excitatory Amino Acid Transporter 4; C493390:Slc1a6 protein, mouse