"Silent" NMDA Synapses Enhance Motion Sensitivity in a Mature Retinal Circuit

Neuron. 2017 Dec 6;96(5):1099-1111.e3. doi: 10.1016/j.neuron.2017.09.058. Epub 2017 Nov 5.

Abstract

Retinal direction-selective ganglion cells (DSGCs) have the remarkable ability to encode motion over a wide range of contrasts, relying on well-coordinated excitation and inhibition (E/I). E/I is orchestrated by a diverse set of glutamatergic bipolar cells that drive DSGCs directly, as well as indirectly through feedforward GABAergic/cholinergic signals mediated by starburst amacrine cells. Determining how direction-selective responses are generated across varied stimulus conditions requires understanding how glutamate, acetylcholine, and GABA signals are precisely coordinated. Here, we use a combination of paired patch-clamp recordings, serial EM, and large-scale multi-electrode array recordings to show that a single high-sensitivity source of glutamate is processed differentially by starbursts via AMPA receptors and DSGCs via NMDA receptors. We further demonstrate how this novel synaptic arrangement enables DSGCs to encode direction robustly near threshold contrasts. Together, these results reveal a space-efficient synaptic circuit model for direction computations, in which "silent" NMDA receptors play critical roles.

Keywords: DSGC; E/I balance; NMDA; SBEM; arithmetic; contrast-invariant; retina; silent synapses; starburst.

MeSH terms

  • Acetylcholine / physiology
  • Animals
  • Glutamic Acid / physiology
  • Mice
  • Motion Perception / physiology*
  • N-Methylaspartate / physiology*
  • Patch-Clamp Techniques
  • Receptors, AMPA / physiology
  • Retina / physiology*
  • Retina / ultrastructure
  • Retinal Bipolar Cells / physiology
  • Retinal Bipolar Cells / ultrastructure
  • Retinal Ganglion Cells / physiology
  • Retinal Ganglion Cells / ultrastructure
  • Signal Transduction / physiology
  • Synapses / physiology*
  • Synapses / ultrastructure
  • gamma-Aminobutyric Acid / physiology

Substances

  • Receptors, AMPA
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • N-Methylaspartate
  • Acetylcholine