Luis De Lecea
Stanford University, CA·Neuroscience
Sleep is not a passive state: specific small groups of brain cells actively push us toward wakefulness or hold us in sleep, and the chemical messengers they release decide how stable a night of sleep is. Work in this lab centers on those arousal-controlling circuits — how they are wired, what makes them fire, and what happens when they malfunction.
- Fields
Neuroscience
Physiology
Medicine & Clinical Research
- Topics
sleep
arousal
hypocretin
- Grants
- 2 known grants, through Apr 2028
What they work on
- Monitor the activity of wake-promoting hypocretin and locus coeruleus neurons in amyloid precursor protein knockin and APP/PS1 mouse models of Alzheimer's disease, and test in slice recordings whether amyloid-beta alters their intrinsic electrical properties.
- Determine whether amyloid-beta changes the activity of neurons active during non-REM and REM sleep and their capacity to maintain normal sleep architecture in Alzheimer's model mice.
- Test whether enhancing sleep pharmacologically or with optogenetics — light-driven control of targeted neurons — delays amyloid-beta accumulation and improves cognitive performance in two mouse models of Alzheimer's disease.
- Map, using viral tracing in NPS-IRES-cre mice, whether the five clusters of Neuropeptide S neurons are interconnected and how they relate anatomically to established arousal circuits.
- Record each Neuropeptide S neuron cluster with fiber photometry across the sleep/wake cycle and during stress and positive stimuli, while controlling for locomotion and body temperature as confounds of arousal.
- Test whether individual Neuropeptide S clusters are necessary for sleep/wake and anxiety behavior using optogenetic and chemogenetic silencing, plus CRISPR-based mutation of the NPS gene in single clusters.
More about the research
Two projects share that focus: one asks how these circuits break down in Alzheimer's disease, and the other dissects a wake-promoting neuropeptide whose circuit mechanisms are largely unknown. Both use mouse genetics plus tools for recording and controlling neural activity.
Why it matters
Fragmented sleep in older adults and in Alzheimer's disease places a heavy burden on patients and caregivers, and poor sleep may itself accelerate disease. Showing that stabilizing arousal circuits slows amyloid accumulation could point to drugs that improve sleep quality and slow decline. Mapping how Neuropeptide S promotes wakefulness and reduces anxiety may identify targets for insomnia, excessive sleepiness and anxiety disorders.
Known grants
From NIH and NSF research grants. Labs often have other funding we can't see.
Closest labs
Qi Wang
Columbia University, NY·Neuroscience
Determine whether long-term chemogenetic stimulation of the locus coeruleus, the brain's main norepinephrine source, delays memory decline and improves synaptic plasticity in amyloid and tau mouse models of Alzheimer's disease.
Kim Dore
University of California-San Diego, CA·Neuroscience
Measure PSD-95 palmitoylation, the fatty tag that anchors this scaffold protein in synapses, across brain regions differently affected by Alzheimer's in APP/PS1 model mice and postmortem human brain samples.
Todd Stincic
Appalachian State University, NC·Neuroscience
Test whether estrogen enhances the activity of dorsomedial orexin neurons, the group linked to arousal, while reducing signaling of lateral neurons tied to food reward, in the mouse hypothalamus.
The school
Stanford University: 87 labs on PI Pages, $1.6B a year on research, 739 research doctorates a year.
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