Neuronal Circuits of NREM Sleep Control in the Basal Forebrain and Midbrain
- Author(s): Chang, Wei-Cheng
- Advisor(s): Dan, Yang
- et al.
Sleep is a fundamental behavior in the animal kingdom. It is essential for optimal cognition,
general health, immune function and neuronal plasticity. Irregular or insufficient sleep may
cause emotional disturbances, abnormal homeostasis of physiological functions. About 30%
adults in the US suffered from insomnia. Therefore, understanding of the sleep‐wake circuit will
contribute to the cure of not only sleep disorders, but also other psychiatric diseases. A crucial
step in understanding the neural circuits controlling sleep is to identify the sleep neurons. In my
thesis, I used transgenic Cre mouse lines, virus‐mediated circuit tracing, and optogenetic
manipulation to identify the sleep‐promoting neurons and dissect the neural circuits for
controlling sleep and arousal.
In chapter 2: The basal forebrain (BF) contains a spatially intermingled diverse population of
neurons that play key roles in multiple brain functions, including sleep‐wake regulation,
attention, and learning/memory. For sleep‐wake regulation, the cholinergic, glutamatergic, and
parvalbumin‐expressing (PV) GABAergic neurons have been shown to promote wakefulness,
whereas the somatostatin‐expressing (SOM) GABAergic neurons promote NREM sleep. To
understand how these cell types in the same area have different functions in sleep‐wake
regulation, we used rabies virus ‐mediated monosynaptic retrograde tracing to label the inputs
and adeno‐associated virus to trace axonal projections. We identified numerous brain areas
connected to the BF. These results reveal the long‐range wiring diagram of the BF circuit with
highly convergent inputs and divergent outputs and point to both functional commonality and
specialization of different BF cell types.
In chapter3: We identified the neurotensin (NTS) neurons in the preoptic area, posterior
thalamus (pTh), and ventrolateral periaqueductal gray (vlPAG) as NREM sleep‐promoting
neurons based on optogenetic manipulation. Using rabies virus‐mediated monosynaptic
retrograde tracing combined with fluorescent in situ hybridization (FISH) experiment, we also
showed that cholecystokinin (CCK) and calcitonin gene‐related peptide alpha (Calca) neurons in
the EW (CCKEW), and NTS neurons in the vlPAG (NTSvlPAG) form reciprocal connections to each
other. These cell types may cooperate to promote NREM sleep.