Application of optical calcium imaging in revealing the neural circuit mechanism of stress-promoting sleep and alleviating anxiety emotion

The rapid increase in the concentration of glucocorticoids in the blood caused by acute stress is conducive to the body's rapid response to environmental threats

The ventral tegmental area (VTA) of the midbrain regulates reward, aversive, and goal-motivated behaviors

On July 1, 2022, the joint research team of William Wisden of Imperial College London and Dong Hailong of Air Force Military Medical University revealed the neural circuit mechanism of acute stress-promoting sleep and relieving anxiety

Figure 1: SDS Acute Stress Flowchart

Sleep is divided into non-rapid eye movement (NREM) and rapid eye movement (REM) sleep

Figure 2: SDS-related sleep-promoting effects relieve anxiety

Experiencing social frustration stress (SDS) can induce anxiety-like behavior in mice, but can significantly reduce anxiety after returning to sleep

Figure 3: Reactivation of SDS-associated VTA inhibitory neurons promotes sleep

Activation of inhibitory neurons in the VTA region by virus-specific labeling of SDS with the c-Fos tool and subsequent reactivation of these activated neurons by chemogenetic techniques reduced sleep latency and increased sleep time in NERM and REM

Even SDS stress did not promote sleep in mice after inhibiting these activated inhibitory neurons

Inhibitory neurons in the VTA region project to multiple brain regions.

Further retrograde tracing of the virus revealed that SDS-activated inhibitory neurons in the VTA region received input from the lateral preoptic area, the paraventricular nucleus of the hypothalamus, and the periaqueductal gray area

Figure 4: Fiber optic calcium imaging recorded the activity of different types of inhibitory neurons in the VTA region

42% of the inhibitory neurons in the VTA region were somatostatin (SST) neurons and 10% were parvalbumin (PV) neurons

Fiber optic calcium imaging revealed increased activity of SST neurons in the VTA region during sleep in NERM and REM, while PV-ergic neurons were activated during wakefulness

After the virus induced apoptosis of SST neurons in the VTA region, the sleep-promoting effect of SDS could be blocked, and the anxiety state was still maintained

Figure 5: Dynamic changes of CRF in the brain recorded by CRF fluorescent probes

After injection of a fluorescent probe encoding corticotropin-releasing factor (CRF) (probe developed by Li Yulong's group at Peking University School of Life Sciences), the fluorescence intensity of CRF in the paraventricular nucleus of the hypothalamus increased after SDS stress, but the fluorescence intensity of CRF in the paraventricular nucleus of the hypothalamus increased after VTA inhibition.

Overall, this paper reveals that acute stress induces anxiety and simultaneously activates SST neurons in the VTA region to promote sleep through the VTA-LH loop, thereby relieving anxiety

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