Ultrastructural analysis of sex differences in nucleus accumbens synaptic connectivity

Anne Marie Wissman, Renee M. May, Catherine S. Woolley*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


Despite robust sex differences in behavioral responses to drugs of abuse, relatively little is known about structural sex differences in synaptic connectivity of reward circuits such as in the nucleus accumbens (NAc). Previously, we showed that distal dendritic spine density on medium spiny neurons in the NAc is higher in females than males, suggesting that sex differences in NAc excitatory synapses could play a role in differential behavioral responses to drugs. In the current study, we used electron microscopy and stereological counting methods to evaluate dendritic spine and shaft synapses, as well as tyrosine hydroxylase-immunoreactive (TH-IR) profiles, in the NAc core of male and female rats. We found an unanticipated rostro-caudal gradient in spine synapse density in females but not males, resulting in a sex difference favoring females in the caudal NAc core. The volume of the NAc was not different between males and females. We also found that the percentage of spines with large spine heads was greater in females in the rostral core. The density of shaft synapses was low compared to spine synapses, and sex differences were minor. The density of TH-IR profiles was not different between males and females, but females had a higher proportion of spines with large heads near TH suggesting a potential sex difference in dopaminergic modulation of large spine synapses. These findings underscore the importance of including both males and females in studies of reward circuitry, and of considering variation along the rostro-caudal axis of the NAc in future studies.

Original languageEnglish (US)
Pages (from-to)181-190
Number of pages10
JournalBrain Structure and Function
Issue number2
StatePublished - Apr 2012


  • Dendritic spine
  • Dopamine
  • Electron microscopy
  • Glutamate
  • Stereology
  • Synapse

ASJC Scopus subject areas

  • Anatomy
  • Neuroscience(all)
  • Histology


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