Serotonin transporters are located on the axons beyond the synaptic junctions

Anatomical and functional evidence

Feng Zhou, Jung Hwa Tao-Cheng, Louis Segu, Tushar Patel, Yun Wang

Research output: Contribution to journalArticle

146 Citations (Scopus)

Abstract

The serotonin (5-HT) transporter (5-HTT) is known to play a role in depression and many 5-HT related diseases, and is the target site for drugs of abuse, such as cocaine, MDMA, and methamphetamine. The major role of the 5-HTT has long been considered to be to inactivate serotonin transmission through the elimination of serotonin at release sites. However, immunocytochemistry using an antibody against the N-terminal of the 5-HTT at the light microscopic (LM) level indicates that the 5-HTT is associated not only with 5-HT varicosities but also with axons. Electron microscopy (EM) reveals that the majority of the 5-HTTs exist on the axolemma outside the synaptic junctions. In studying whether axonal 5-HTTs are involved in the uptake of 5-HT, we found with autoradiography that [3H]citalopram bound to all major 5-HT fibers, not only in the terminal regions, but also in 5-HT axonal bundles such as the cingulum bundle and medial forebrain bundle. Furthermore, voltammetry recordings indicated that serotonin axonal bundles were actively engaged in high affinity serotonin uptake. The evidence indicates that 5-HTTs on 5-HT axons away from the synapse are likely to be functional in a manner similar to the terminal 5-HTT for serotonin uptake. It also suggests that the role of the 5-HTT may not only be for the termination of synaptic transmission, but also for the regulation of 5-HT through extrasynaptic (volume) transmission. Our findings may also impact the understanding of the sites of action of selective serotonin reuptake inhibitors and drug entry into serotonin neurons via the numerous axonal sites.

Original languageEnglish
Pages (from-to)241-254
Number of pages14
JournalBrain Research
Volume805
Issue number1-2
DOIs
StatePublished - Sep 14 1998

Fingerprint

Serotonin Plasma Membrane Transport Proteins
Axons
Serotonin
Medial Forebrain Bundle
N-Methyl-3,4-methylenedioxyamphetamine
Citalopram

Keywords

  • Autoradiography
  • Citalopram
  • Cocaine
  • Depression
  • Electron microscopy
  • High-affinity uptake
  • Immunocytochemistry
  • MDMA
  • Methamphetamine
  • Paroxetine
  • Synapse
  • Voltammetry

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Serotonin transporters are located on the axons beyond the synaptic junctions : Anatomical and functional evidence. / Zhou, Feng; Tao-Cheng, Jung Hwa; Segu, Louis; Patel, Tushar; Wang, Yun.

In: Brain Research, Vol. 805, No. 1-2, 14.09.1998, p. 241-254.

Research output: Contribution to journalArticle

Zhou, Feng ; Tao-Cheng, Jung Hwa ; Segu, Louis ; Patel, Tushar ; Wang, Yun. / Serotonin transporters are located on the axons beyond the synaptic junctions : Anatomical and functional evidence. In: Brain Research. 1998 ; Vol. 805, No. 1-2. pp. 241-254.
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