Early-life experiences altered the maturation of the lateral habenula in mouse models, resulting in behavioural disorders in adulthood.
Summary: Discovering a specific period in early life when stress sensitivity is high that affects the state of mind after growth in mice.
A research group of Tomoya Nakamura, Assistant Professor, and Hiroyuki Ichijo, Professor, Department of Anatomy and Neuroscience, Faculty of Medicine, University of Toyama, has revealed that stress experiences at a specific period in early life cause maturation changes in neural circuits that control emotions, as well as anxiety and depression-like behaviors in adults. These changes in neuronal circuits are thought to be a mechanism in the brain for the development of anxiety and depression, and are expected to lead to research on prevention and treatment.
- The neural circuits in the lateral habenula, which controls emotion, mature in four stages.
- In mice that were stressed during the maturation of the lateral habenula (postnatal day 10-20; mice were weaned at about postnatal day 20), the maturation of the neural circuits was altered, and the mice exhibited anxiety and depression-like behavior after growth.
- These results indicate that circuit alterations in the lateral habenula are more likely to occur during early life (postnatal 10-20 day), and that experiences during this period are important for emotional maturation. This circuit alteration is thought to be a mechanism in the brain by which anxiety and depression develop. It also suggests that experiences during a particular period of early life are critical in preventing lifelong anxiety and depression. This study will provide the basis for research on the treatment and prevention of anxiety and depression and the effects of early life.
Background and over view
Abnormally high activity in the lateral habenula (LHb) causes anxiety/depression-like behaviors in animal experimental models. It has been also reported in humans that excessive stress in early-life is correlated to the onset of psychiatric disorders in adults. These raise a problem whether LHb maturation is affected under influence of early-life experiences, which could govern behaviors throughout life.
LHb maturation was examined in mice based on neuronal activity marker and plastic components: Zif268/Egr1, parvalbumin (PV), and perineuronal nets. The effect of early-life stress was examined by using repeated maternal deprivation.
First, a transient highly sensitive period of the LHb under the stresses was found. LHb matured through four stages: the first (postnatal day 1-9, i.e. P1-9), second (P10-20), third (around P35), and fourth (after P35). In P10-20, LHb was highly sensitive to the stresses. Second, experience-dependent LHb maturation was shown. Only mice exposed to chronic stress during P10-20 exhibited LHb-specific changes at P60: abnormally high-stress reactivity shown by Zif268/Egr1 and fewer PV neurons. These mice showed anxiety/depression-like behaviors in the light-dark box test/forced swim test.
The early-life stress in P10-20 resulted in the late effects in adulthood: hyperactivity in the LHb and anxiety/depression, indicating differences in neuronal plasticity between stages of LHb maturation.
Early-life experiences altered the maturation of the lateral habenula in mouse models, resulting in behavioural disorders in adulthood
Tomoya Nakamura, Kohei Kurosaki, Munenori Kanemoto, Masakiyo Sasahara, Hiroyuki Ichijo.
Journal of Psychiatry and Neuroscience 4;46(4):E480-E489. 2021.