The Waking Brain team – NEURAL CIRCUITS FOR AROUSAL AND SLEEP
Our research aims to unravel the brain circuits of arousal and sleep to understand how their interaction generates unique behavioral and cognitive abilities, and how they contribute to mental illness.
Levels of arousal can describe different states of wakefulness on the spectrum from sleep, or drowsiness, to wake states of alertness, sustained attention or motivated behaviors. Instability in the regulation of arousal is commonly observed in neuropsychiatric disorders, particularly in affective disorders such as depression or attention deficit hyperactivity disorder (ADHD) subserving comorbid symptoms of generalized anxiety or addiction.
Our group employs a multidisciplinary approach in mouse models focusing on the brain circuits involved in the regulation of arousal using optogenetics, neural circuit tracing and in vivo electrophysiological and imaging techniques to find mechanistic explanations for what controls the boundaries between arousal, hypoarousal and hyperarousal, and the impacts of maladaptive arousal on sleep and behavior contributing to cognitive and emotional impairments.
The GABAergic Gudden’s dorsal tegmental nucleus: a new relay for serotonergic regulation of sleep-wake behavior in the mouse.
Chazalon M., Dumas S., Bernard J.-F., Sahly I., Tronche F., deKerchove d’Exaerde A., Hamon M., Adrien J., Fabre V.*, Bonnavion P.* Neuropharmarcology, 138:315-30, 2018. *co-last authors.
Identification of a new circuit underlying serotonergic arousing effects through the GABAergic Gudden dorsal tegmental nucleus directly connected to wake centers in the posterior hypothalamus.
Hypothalamic Tuberomammillary Nucleus Neurons: Electrophysiological Diversity and Essential Role in Arousal Stability.
Fujita A.*, Bonnavion P.*#, Wilson M.H., Mickelsen L.E., Bloit J., de Lecea L., Jackson A.C. Journal of Neuroscience, 37: 9574-92, 2017. *co-first, #co-corresponding authors.
Proof-of-concept that TMN histamine neurons are necessary for arousal maintenance and that their inhibition is sufficient to elicit sleep.
Antagonistic interplay between hypocretin and leptin in the lateral hypothalamus regulates stress responses.
Bonnavion P., Jackson A.C., Carter M.C., de Lecea L. Nature Communication. 6: 6266, 2015.
Sustained activation of hypothalamic hypocretin system in metabolic disbalance drives aversive hyperarousal and generalized stress controlled by a local GABAergic circuit involving leptin brain signaling. Relevance to new therapeutic strategies involving hypocretin and leptin in anxiety-related eating disorders and panic attacks (NARSAD Young Investigator prize).
A mechanism for Hypocretin-mediated sleep-to-wake transitions.
Carter M.E., Brill J., Bonnavion P.,Huguenard J.R., Huerta R., de Lecea L. Proceedings of the National Academy of Sciences. USA. 109(39): 2635-44, 2012.
LC noradrenergic neurons activation by hypothalamic hypocretin is necessary to promote and maintain arousal.
Heterogeneous distribution of the 5-HT1A receptor mRNA in chemically identified neurons of the mouse rostral brainstem.
Bonnavion P., Bernard J.-F., Hamon M., Adrien J., Fabre V. Journal of Comparative Neurology. 518(14): 2744-70, 2010.
Evidence that waking serotonergic raphe nuclei are highly heterogeneous targeting predominantly pontine GABAergic cells and demonstrating that, contrary to the canonical dogma, 5-HT neuronal subsets are differentially regulated by negative feedback loop (Albert Sezary Prize).
Book Chapters & Reviews:
Serotonin and Sleep.
Fabre, V., Krystal, A. & Bonnavion, P. Principles and Practice of Sleep Medicine, 7th edition. Dement, W.C., Kryger M.H., Roth T. (Eds). Elsevier. (in press)
It takes two to tango: Dorsal direct and indirect pathways orchestration of motor learning and behavioral flexibility.
Bonnavion, P., Pozuelo Fernandez, E., Varin, C., de Kerchove d’Exaerde, A. Neurochemistry international, 124, 200-214, 2019.
Pharmacosynthetic Deconstruction of Sleep-Wake Circuits in the Brain.
Varin, C. & Bonnavion, P. Handbook of experimental pharmacology, 253, 153-206, 2019.
Hubs and spokes of the lateral hypothalamus: cell types, circuits and behaviour.
Bonnavion, P., Mickelsen, L. L., Fujita, A., De Lecea, L., & Jackson, A. A. (2016). Journal of physiology, 594(22), 6443-6462, 2016.