Sexual dimorphism in locus coeruleus dendritic morphology: a structural basis for sex differences in emotional...

Stress-related psychiatric disorders, such as depression and anxiety, affect a disproportionate number of women. We previously demonstrated that the major brain norepinephrine (NE)-containing nucleus, locus coeruleus (LC) is more sensitive to stressors and to the stress-related neuropeptide, corticotropin-releasing factor (CRF) in female compared to male rats. Because the LC-NE system is a stress-responsive system that is thought to be dysregulated in affective disorders, sex differences in LC structure or function could play a role in female vulnerability to these diseases. The present study used different approaches to compare LC dendritic characteristics between male and female rats. Immunofluorescence labeling of tyrosine hydroxylase, the norepinephrine synthetic enzyme, revealed that LC dendrites of female rats extend further into the peri-LC region, covering a significantly greater area than those of males. Optical density measurements of dendrites in the peri-LC revealed increased dendritic density in females compared to their male counterparts. Additionally, immunoreactivity for synaptophysin, a synaptic vesicle protein, was significantly greater in the LC in female rats, suggesting an increased number of synaptic contacts onto LC processes. Individual LC neurons were juxtacellularly labeled with neurobiotin in vivo for morphological analysis. LC dendritic trees of females were longer and had more branch points and ends. Consistent with this, Sholl analysis determined that, compared to males, LC dendrites of females had a more complex pattern of branching. The greater dendritic extension and complexity seen in females predicts a higher probability of communication with diverse afferents that terminate in the peri-LC. This may be a structural basis for heightened arousal in females, an effect which may, in part, account for the sex bias in incidence of stress-related psychiatric disorders.