Receptor and transmitter release properties set the time course of retinal inhibition

J Neurosci. 2006 Sep 13;26(37):9413-25. doi: 10.1523/JNEUROSCI.2591-06.2006.

Abstract

Synaptic inhibition is determined by the properties of postsynaptic receptors, neurotransmitter release, and clearance, but little is known about how these factors shape sensation-evoked inhibition. The retina is an ideal system to investigate inhibition because it can be activated physiologically with light, and separate inhibitory pathways can be assayed by recording from rod bipolar cells that possess distinct glycine, GABA(A), and GABA(C) receptors (R). We show that receptor properties differentially shape spontaneous IPSCs, whereas both transmitter release and receptor properties shape light-evoked (L) IPSCs. GABA(C)R-mediated IPSCs decayed the slowest, whereas glycineR- and GABA(A)R-mediated IPSCs decayed more rapidly. Slow GABA(C)Rs determined the L-IPSC decay, whereas GABA(A)Rs and glycineRs, which mediated rapid onset responses, determined the start of the L-IPSC. Both fast and slow inhibitory inputs distinctly shaped the output of rod bipolar cells. The slow GABA(C)Rs truncated glutamate release, making the A17 amacrine cell L-EPSCs more transient, whereas the fast GABA(A)R and glycineRs reduced the initial phase of glutamate release, limiting the peak amplitude of the L-EPSC. Estimates of transmitter release time courses suggested that glycine release was more prolonged than GABA release. The time course of GABA release activating GABA(C)Rs was slower than that activating GABA(A)Rs, consistent with spillover activation of GABA(C)Rs. Thus, both postsynaptic receptor and transmitter release properties shape light-evoked inhibition in retina.

Publication types

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

MeSH terms

  • Amacrine Cells / drug effects
  • Amacrine Cells / metabolism
  • Animals
  • Female
  • Glutamic Acid / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neural Pathways / cytology
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neurotransmitter Agents / metabolism*
  • Neurotransmitter Agents / pharmacology
  • Photic Stimulation
  • Reaction Time / drug effects
  • Reaction Time / physiology
  • Receptors, GABA / drug effects
  • Receptors, GABA / metabolism
  • Receptors, Glycine / drug effects
  • Receptors, Glycine / metabolism
  • Receptors, Neurotransmitter / agonists
  • Receptors, Neurotransmitter / antagonists & inhibitors
  • Receptors, Neurotransmitter / metabolism*
  • Retina / cytology
  • Retina / drug effects
  • Retina / metabolism*
  • Retinal Bipolar Cells / drug effects
  • Retinal Bipolar Cells / metabolism
  • Synaptic Membranes / drug effects
  • Synaptic Membranes / metabolism
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*
  • Time Factors
  • Vision, Ocular / drug effects
  • Vision, Ocular / physiology

Substances

  • Neurotransmitter Agents
  • Receptors, GABA
  • Receptors, Glycine
  • Receptors, Neurotransmitter
  • Glutamic Acid