Serotonin released from amacrine neurons is scavenged and degraded in bipolar neurons in the retina

J Neurochem. 2009 Oct;111(1):1-14. doi: 10.1111/j.1471-4159.2009.06270.x. Epub 2009 Jul 8.


The neurotransmitter serotonin is synthesized in the retina by one type of amacrine neuron but accumulates in bipolar neurons in many vertebrates. The mechanisms, functions and purpose underlying serotonin accumulation in bipolar cells remain unknown. Here, we demonstrate that exogenous serotonin transiently accumulates in a distinct type of bipolar neuron. KCl-mediated depolarization causes the depletion of serotonin from amacrine neurons and, subsequently, serotonin is taken-up by bipolar neurons. The accumulation of endogenous and exogenous serotonin by bipolar neurons is blocked by selective reuptake inhibitors. Exogenous serotonin is specifically taken-up by bipolar neurons even when serotonin-synthesizing amacrine neurons are destroyed; excluding the possibility that serotonin diffuses through gap junctions from amacrine into bipolar neurons. Further, inhibition of monoamine oxidase A prevents the degradation of serotonin in bipolar neurons, suggesting that monoamine oxidase A is present in these neurons. However, the vesicular monoamine transporter 2 is present only in amacrine cells suggesting that serotonin is not transported into synaptic vesicles and reused as a transmitter in the bipolar neurons. We conclude that the serotonin-accumulating bipolar neurons perform glial functions in the retina by actively transporting and degrading serotonin that is synthesized in neighboring amacrine cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amacrine Cells / drug effects
  • Amacrine Cells / metabolism*
  • Animals
  • Animals, Newborn
  • Chickens
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Enzyme Inhibitors / pharmacology
  • Homeodomain Proteins / metabolism
  • Potassium Chloride / pharmacology
  • Retina / cytology*
  • Retinal Bipolar Cells / drug effects
  • Retinal Bipolar Cells / metabolism*
  • Serotonin / metabolism*
  • Serotonin / pharmacology
  • Serotonin Uptake Inhibitors / pharmacology
  • Sertraline / pharmacology
  • Vesicular Monoamine Transport Proteins / genetics
  • Vesicular Monoamine Transport Proteins / metabolism
  • Zimeldine / pharmacology


  • Enzyme Inhibitors
  • Homeodomain Proteins
  • Serotonin Uptake Inhibitors
  • Vesicular Monoamine Transport Proteins
  • Serotonin
  • Zimeldine
  • Potassium Chloride
  • Sertraline