Posts classified under: Circadian and Sleep Medicine

Felix Schweizer, Ph.D.

Faculty Member

Professor
Chair, Graduate Interdepartmental Program for Neuroscience

Department of Neurobiology
David Geffen School of Medicine
University of California, Los Angeles

Office
Center for Health Sciences 63-323
650 Charles E Young Dr S,
Los Angeles, CA 90095

 

Biography

Felix E. Schweizer was born in Basel, Switzerland and conducted his graduate research in the laboratory of Prof. Max M. Burger under the direction of Dr. Theo Schafer. He received his PhD degree in biochemistry summa cum laude from the University of Basel in 1989. From 1990 to 1994, he was a post-doctoral fellow in the Department of Molecular and Cellular Physiology at Stanford University in the laboratory of Prof. Richard W. Tsien. From 1994 to 1998, he was postdoctoral fellow in the Department of Neurobiology at Duke University in the laboratory of Professor George J. Augustine. Dr. Schweizer joined the Department of Neurobiology in the David Geffen School of Medicine at UCLA in 1998 as Assistant Professor and was promoted to Full Professor in 2010. Dr. Schweizer’s research interests concern the molecular mechanisms by which neurons communicate, the regulation of communication by neurons and how alterations in neuronal communication might contribute to neuronal diseases. The Schweizer laboratory uses electrophysiological and optical tools to investigate the dynamic molecular mechanisms underlying the regulation of neurotransmitter release. We are particularly interested in the role of protein ubiquitination in regulating neuronal excitability and synaptic transmission. In collaboration with Dr. James Wohlschlegel, we used multiplexed SILAC and identified synaptic proteins that are dynamically regulated. More recently, in collaboration with Dr. David Krantz, we are using pesticides linked to neuro-degenerative disorders as unbiased tools identify novel pathways that might be involved in early signs of degeneration. In addition, we are characterizing transmission at the first synapse of the vestibular system, i.e. between utricular sensory hair cells and primary afferent neurons. In collaboration with Dr. Larry Hoffman we are finding that changing the gravitational load alters synaptic structures. We are now using serial EM and EM tomography in addition to physiology and cell biology to define in more detail the transfer function between head-movement input and afferent nerve-firing output.

Jerome Siegel, Ph.D.

Faculty Member

Professor in Residence
Chief, Neurobiology Research, Sepulveda VA Medical Center
Department of Psychiatry & Biobehavioral Sciences
David Geffen School of Medicine
University of California, Los Angeles

 

Bldg 7, Greater Los Angeles Health System, Sepulveda
16111 Plummer St, North Hills,
Los Angeles, CA 91343

Research:

Our primary interest is in understanding the evolution, function and disorders of sleep. We are analyzing the brainstem-forebrain interactions responsible for the control of muscle tone in waking and across the sleep cycle. This is of importance in understanding REM sleep behavior disorder, cataplexy and sleep apnea. We are studying the phylogeny of sleep by investigating the physiology and neurochemistry of sleep in reptiles, marine mammals and human hunter gatherers.

A major focus of the laboratory is on narcolepsy, its anatomy, pathophysiology and treatment. We found that human narcolepsy is linked to a loss of locus coeruleus and hypocretin neurons as well as changes in other neuronal groups. The loss of locus coeruleus neurons, which project both rostrally as part of the ascending reticular activating system, and caudally to spinal motor systems, can explain the unique symptoms of narcolepsy, sleepiness and cataplexy. The loss of hypocretin (orexin) neurons, which we find are linked to opioid addiction, can explain the elevated incidence of depression in narcolepsy. We are investigating ways of controlling and reversing the symptoms of narcolepsy in narcoleptic animals and in humans.

See two recent publications below:

Thannickal, T.C., Wu, Ming-Fung, Cornford, M.C. and Siegel, Jerome M., Human narcolepsy is linked to degeneration of both locus coeruleus and hypocretin neurons.  Nature Communications [PMID 41904178] 2026. https://doi.org/10.1038/s41467-026-70899-x

McGregor, R., Wu, Ming-Fung, Thannickal, T.C., Siegel, Jerome M. Opioid-induced neuroanatomical, microglial and behavioral changes are blocked by suvorexant without diminishing opioid analgesia. Nature Mental Health. PMCID: PMC11845277  NIHMSID: NIHMS2053716  PMID: 39989723, 2024

Publications

https://www.ncbi.nlm.nih.gov/myncbi/jerome.siegel.1/bibliography/public/

Contrary to some speculation in the media commenting on our recent locus coeruleus paper (above), we see no evidence that the loss of locus coeruleus neurons is responsible for “more severe narcolepsy.” Rather, we conclude that both the sleepiness and cataplexy of narcolepsy are likely due to the loss of locus coeruleus neurons. Locus coeruleus neurons have both ascending projections to the forebrain and descending projections to spinal cord motor neurons (PMID 32943779).
Hypocretin neurons are active in relation to elevated mood (PMID: 36564940: PMID 32963102; PMID: 39989723), not changes in sleepiness or muscle tone, the major symptoms of narcolepsy. The loss of hypocretin neurons may be responsible for the greatly elevated incidence of depression in narcolepsy.