1. Neuronal circuits underly sleep-wake behaviors.

The ventral basal ganglia play a crucial role in regulating arousal and related motivation. We established causal connections between the activity of dopamine D1 receptor-positive neurons in the Nucleus accumbens (NAc) and specific behaviors such as sleep-wake cycles, locomotion, and feeding behaviors (Nat Commun, 2018). Notably, both NAc D1R and D2R neurons project to the ventral pallidum (VP). Further investigations revealed that GABAergic neurons in the VP are involved in regulating arousal related to motivation through their connections with the ventral tegmental area (Mol Psychiatry, 2021). Additionally, we discovered that VP glutamatergic neurons have a distinct role in modulating cortical activity and influencing low motivation (iScience, 2023). These findings provide valuable insights into the complex neural circuits underlying arousal, motivation, and related behaviors, shedding light on potential therapeutic targets for conditions involving dysregulation in these processes.

2. Circuit-modified adult hippocampal neurogenesis activity dependently regulates memory and emotion.

Adult hippocampal neurogenesis is a crucial process that plays a significant role in memory and emotional processing. It is dynamically regulated by neural circuit activity. However, it remained uncertain whether manipulating neural circuit activity could produce substantial neurogenic effects capable of influencing behavior. Our research has shed light on this matter. We discovered that the hypothalamic supramammillary nucleus (SuM) synchronizes with the dentate gyrus (DG) to modulate spatial memory retrieval by releasing glutamate (eLife, 2020). Subsequently, we identified a pivotal hypothalamic circuit that links novelty signals to the generation and maturation of adult-born neurons (ABNs). This finding emphasizes the role of activity-dependent modifications in circuit-connected ABNs in regulating behavior (Nature Neuroscience, 2022). Building on these insights, we proposed that a multi-faceted approach to enhance adult-born neurons, encompassing their numbers, properties, and activity levels, is essential for improving behavioral outcomes (Curr Opin Neurobiol, 2023). We then applied this strategy to rescue cognitive and emotional deficits in Alzheimer's disease and conducted a functional dissection of the underlying mechanism by which ABNs activity-dependently regulate memory (Cell Stem Cell, 2023). These findings hold promise for developing novel interventions to address cognitive and emotional impairments in Alzheimer's disease and advance our understanding of the role of adult-born neurons in memory regulation.

3. sleep disorders and cognitive deficits in in Alzheimer’s disease

Alzheimer's disease (AD) patients commonly experience sleep disorders, alongside cognitive deficits, particularly in memory functions. Our research focuses on addressing these disturbances in sleep-wake patterns and memory impairment by targeting the affected brain regions. Additionally, we aim to delve into the intricate cellular and molecular mechanisms underlying these memory-related brain regions to develop potential therapeutic interventions.

4. Neurocircuit mechanisms of chronic pain-induced sleep disorders

Chronic pain often leads to the development of sleep disturbances. However, the precise neural circuit mechanisms responsible for sleep disorders in chronic pain have remained largely unknown. Our research identifies pyramidal neurons (PNs) in the anterior cingulate cortex (ACC) specifically control chronic-pain-induced insomnia via enhanced activity and plasticity of ACC-dorsal medial striatum (DMS) dopamine D1R neuron synapses (Neuron, 2024). These findings address a long-standing gap in the understanding of how chronic pain induces sleep disorders and shed light on potential therapeutic targets for chronic-pain-induced sleep disorders.