Afferent and efferent projections of the rostral anterior cingulate cortex in young and middle-aged mice

Published on August 17, 2022

Just like mental health issues affecting the young have gained global attention, this study focuses on the rostral anterior cingulate cortex (rACC) and how its neural circuits change with age. By injecting tracer viruses into the rACC of young and middle-aged mice, researchers examined the afferent (incoming) and efferent (outgoing) connections of the rACC at different ages and in both male and female mice. In young and middle-aged mice, they found that the afferents of the rACC come primarily from the amygdala and cerebral cortex, while the efferents mainly project to the thalamus. Interestingly, they discovered that the connection between the amygdala and rACC remains relatively stable throughout life, but the connection between the rACC and thalamus decreases significantly with age in both male and female mice. This comprehensive analysis sheds light on the neural projections of the rACC in mice of different ages and sexes, providing a foundation for future targeted research.

Research shows that across life, the incidence of mental illness is highest in the young. In the context of the COVID-19 pandemic, mental health issues of the young in particular have received global attention. The rostral anterior cingulate cortex (rACC) plays an important role in psychiatric disorders and chronic pain-psychiatric comorbidities. However, it remains unknown whether or how the afferent and efferent circuits of the rACC change with aging. In this study, we microinjected a retrograde tracer virus and an anterograde trans-monosynaptic virus into the rACC of young and middle-aged mice (both male and female), and systematically and quantitatively analyzed the whole-brain afferent and efferent connections of rACC at different ages and sexes. Notably, in young and middle-aged mice, afferents of the rACC belong to four groups of brain structures arising mainly from the amygdala [mainly basolateral amygdaloid nucleus (BLA)] and cerebral cortex (mainly orbital cortex), with a small part originating from the basal forebrain and thalamus. In contrast, efferents of the rACC belong to four groups of brain structures mainly projecting to the thalamus (mainly ventral anterior-lateral/ventromedial thalamic nucleus (VAL/VM)], with a very small part projecting to the amygdala, basal forebrain, and cerebral cortex. Compared with young mice, the BLA-rACC circuit in middle-aged mice (male and female) did not change significantly, while the rACC-VAL/VM circuit in middle-aged mice (male and female) decreased significantly. In conclusion, this study comprehensively analyzed the input-output neural projections of rACC in mice of different ages and sexes and provided preliminary evidence for further targeted research.

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