Tuning arousal with optogenetic modulation of locus coeruleus neurons.

Neural activity in the noradrenergic locus coeruleus correlates with periods of wakefulness and arousal. However, whether tonic or phasic activity in these neurons is necessary or sufficient to induce behavioral state transitions and promote long-term arousal is unresolved. We used optogenetic tools in mice to demonstrate a frequency-dependent, causal relationship between locus coeruleus firing, cortical activity, sleep-to-wake transitions, and general locomotor arousal. Surprisingly, we also found that sustained, high-frequency stimulation of the locus coeruleus at frequencies 5 Hz and above caused reversible behavioral arrests. These results suggest that the locus coeruleus is finely tuned to regulate organismal arousal and that bursts of noradrenergic over-excitation cause behavioral attacks similar to those observed in neuropsychiatric disorders.

去甲肾上腺素能蓝斑核的神经活动与清醒和觉醒时期相关。然而，这些神经元的紧张性或相位性活动对于诱导行为状态转变和促进长期觉醒是否必要或充分，仍未得到解决。我们在小鼠中使用光遗传学工具证明了蓝斑核放电、皮质活动、睡眠 - 觉醒转换以及整体运动觉醒之间存在频率依赖性的因果关系。令人惊讶的是，我们还发现，以5赫兹及以上频率对蓝斑核进行持续的高频刺激会导致可逆的行为停滞。这些结果表明，蓝斑核经过精细调节以调控机体的觉醒，并且去甲肾上腺素能过度兴奋的爆发会导致类似于在神经精神疾病中观察到的行为发作。