Age- and sex-dependent effects of stressors on activity of the nucleus reuniens of the thalamus

Abstract

Background

Stress is a significant socio-environmental risk factor for schizophrenia, with its impact varying with age and sex. Male rats are more vulnerable to the long-term effecct of stress during early adolescence, whereas females are more affected during late adolescence, with both demonstrating a stress-induced hyperdopaminergic state and ventral hippocampal hyperexcitability. The nucleus reuniens of the thalamus (RE) plays a crucial role in modulating hippocampal-prefrontal connectivity and dopamine activity. This study investigated the effect of stress during neurodevelopment on RE activity in both sexes.

Study design

Sprague-Dawley rats were subjected to a 10-day footshock and restraint stress protocol during early adolescence (Post-natal day [PD] 31–40) or late adolescence (PD41–50) periods. Electrophysiological RE recordings were conducted 1–2 and 5–6 weeks post-stress.

Study results

Early adolescence stress did not affect the number of spontaneously active RE neurons in males and females after 1–2 or 5–6 weeks, but it increased the proportion of RE neurons firing in bursts in females. Late adolescence stress increased the number of spontaneously active RE neurons in females at both 1–2 and 5–6 weeks. Females had fewer active RE neurons than males starting earlier in adulthood but not at a younger age (PD47–54). This shows an age-dependent effect on female RE activity.

Conclusion

Stress had sex-specific effects on RE neuron activity of females, with late adolescence stress increasing the number of spontaneous RE neurons, while early adolescence stress influenced burst firing. Therefore, stress-induced changes in RE activity during adolescence may contribute to females' vulnerability to neuropathology.