Conditional Knock-Out of Vesicular GABA Transporter Gene from Starburst Amacrine Cells Reveals the Contributions of Multiple Synaptic Mechanisms Underlying Direction Selectivity in the Retina

J Neurosci. 2015 Sep 23;35(38):13219-32. doi: 10.1523/JNEUROSCI.0933-15.2015.

Abstract

Direction selectivity of direction-selective ganglion cells (DSGCs) in the retina results from patterned excitatory and inhibitory inputs onto DSGCs during motion stimuli. The inhibitory inputs onto DSGCs are directionally tuned to the antipreferred (null) direction and therefore potently suppress spiking during motion in the null direction. However, whether direction-selective inhibition is indispensable for direction selectivity is unclear. Here, we selectively eliminated the directional tuning of inhibitory inputs onto DSGCs by disrupting GABA release from the presynaptic interneuron starburst amacrine cell in the mouse retina. We found that, even without directionally tuned inhibition, direction selectivity can still be implemented in a subset of On-Off DSGCs by direction-selective excitation and a temporal offset between excitation and isotropic inhibition. Our results therefore demonstrate the concerted action of multiple synaptic mechanisms for robust direction selectivity in the retina. Significance statement: The direction-selective circuit in the retina has been a classic model to study neural computations by the brain. An important but unresolved question is how direction selectivity is implemented by directionally tuned excitatory and inhibitory mechanisms. Here we specifically removed the direction tuning of inhibition from the circuit. We found that direction tuning of inhibition is important but not indispensable for direction selectivity of DSGCs' spiking activity, and that the residual direction selectivity is implemented by direction-selective excitation and temporal offset between excitation and inhibition. Our results highlight the concerted actions of synaptic excitation and inhibition required for robust direction selectivity in the retina and provide critical insights into how patterned excitation and inhibition collectively implement sensory processing.

Keywords: direction selectivity; retina; starburst amacrine cell; synaptic excitation; synaptic inhibition; vesicular GABA transporter.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / genetics
  • Amacrine Cells / cytology
  • Amacrine Cells / physiology*
  • Animals
  • Choline O-Acetyltransferase / genetics
  • Choline O-Acetyltransferase / metabolism
  • Dendrites / metabolism
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / genetics
  • Light
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Optogenetics
  • Orientation / physiology*
  • Patch-Clamp Techniques
  • Receptors, Dopamine D4 / genetics
  • Receptors, Dopamine D4 / metabolism
  • Retina / cytology
  • Statistics, Nonparametric
  • Synapses / physiology*
  • Vesicular Inhibitory Amino Acid Transport Proteins / deficiency*
  • Vesicular Inhibitory Amino Acid Transport Proteins / genetics
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Drd4 protein, mouse
  • Luminescent Proteins
  • Vesicular Inhibitory Amino Acid Transport Proteins
  • Viaat protein, mouse
  • Receptors, Dopamine D4
  • gamma-Aminobutyric Acid
  • Choline O-Acetyltransferase