Searching for sleep in all the right places: My career in sleep research.

My research has always focused on sleep, whether monitoring neural activity (microwires, c-Fos, calcium imaging), triggering it with optogenetics or pharmacologically (anandamide, cholinergic agonists), or measuring levels of endogenous sleep agents such as adenosine. A recurring theme of my research is to use new tools to find the sweet spot in the brain where the signal to sleep begins. My goal is to identify the circuit, determine whether it degrades with age or disease, and repair the circuit when it fails.

Role of the Locus Coeruleus Arousal Promoting Neurons in Maintaining Brain Criticality across the Sleep-Wake Cycle.

Sleep control depends on a delicate interplay among brain regions. This generates a complex temporal architecture with numerous sleep-stage transitions and intermittent fluctuations to micro-states and brief arousals. These temporal dynamics exhibit hallmarks of criticality, suggesting that tuning to criticality is essential for spontaneous sleep-stage and arousal transitions.

Most dynorphin neurons in the zona incerta-perifornical area are active in waking relative to non-rapid-eye movement and rapid-eye movement sleep.

Dynorphin is an endogenous opiate localized in many brain regions and spinal cord, but the activity of dynorphin neurons during sleep is unknown. Dynorphin is an inhibitory neuropeptide that is coreleased with orexin, an excitatory neuropeptide. We used microendoscopy to test the hypothesis that, like orexin, the dynorphin neurons are wake-active.

Unilateral optogenetic stimulation of Lhx6 neurons in the zona incerta increases REM sleep.

To determine how a waking brain falls asleep researchers have monitored and manipulated activity of neurons and glia in various brain regions. While imaging Gamma-Aminobutyric Acid (GABA) neurons in the zona incerta (ZI) we found a subgroup that anticipates onset of NREM sleep (Blanco-Centurion C, Luo S, Vidal-Ortiz A, Swank C, Shiromani PJ. Activity of a subset of vesicular GABA-transporter neurons in the ventral ZI anticipates sleep onset.