Glutamate transporters are involved in direct inhibitory synaptic transmission in the vertebrate retina

Open Biol. 2024 Jul;14(7):240140. doi: 10.1098/rsob.240140. Epub 2024 Jul 31.

Abstract

In the central nervous system of vertebrates, glutamate serves as the primary excitatory neurotransmitter. However, in the retina, glutamate released from photoreceptors causes hyperpolarization in post-synaptic ON-bipolar cells through a glutamate-gated chloride current, which seems paradoxical. Our research reveals that this current is modulated by two excitatory glutamate transporters, EAAT5b and EAAT7. In the zebrafish retina, these transporters are located at the dendritic tips of ON-bipolar cells and interact with all four types of cone photoreceptors. The absence of these transporters leads to a decrease in ON-bipolar cell responses, with eaat5b mutants being less severely affected than eaat5b/eaat7 double mutants, which also exhibit altered response kinetics. Biophysical investigations establish that EAAT7 is an active glutamate transporter with a predominant anion conductance. Our study is the first to demonstrate the direct involvement of post-synaptic glutamate transporters in inhibitory direct synaptic transmission at a central nervous system synapse.

Keywords: glutamate; inhibitory; synaptic; transmission; transporters; vertebrates.

MeSH terms

  • Amino Acid Transport System X-AG* / genetics
  • Amino Acid Transport System X-AG* / metabolism
  • Animals
  • Glutamic Acid / metabolism
  • Mutation
  • Retina* / metabolism
  • Retinal Bipolar Cells / metabolism
  • Synaptic Transmission*
  • Zebrafish Proteins* / genetics
  • Zebrafish Proteins* / metabolism
  • Zebrafish* / metabolism

Substances

  • Amino Acid Transport System X-AG
  • Zebrafish Proteins
  • Glutamic Acid