Christopher S. Leonard, Ph.D.
Professor of Physiology
Department of Physiology
Basic Sciences Building
New York Medical College
Valhalla, NY 10595
My lab is interested in the neural mechanisms underlying arousal, sleep and motivated states. Indeed, how and why we sleep are central unsolved questions in medicine and nearly 40 million people in the United States are estimated to experience chronic or intermittent sleep disorders such as narcolepsy, sleep apnea, restless leg syndrome and insomnia. We are particularly interested in understanding the cellular, synaptic and circuit changes that give rise to these disorders. We utilize whole-cell patch clamp recordings and simultaneous Ca2+ imaging methods in brain slices from normal and transgenic mice in order to understand how neurons involved with regulating wakefulness and sleep integrate their synaptic inputs and encode these into action potential firing. We have worked extensively on defining the functions of muscarinic, nicotinic and orexin receptors using both pharmacology and knockout approaches in mesopontine cholinergic and serotonergic neurons and we have significant experience working on the specialized firing properties of fast-spiking neocortical GABA neurons. At the circuit level, we are utilizing optogenetic and chemogenetic probes expressed by viral vectors and reporter mice to identify and study the operation of circuits regulating sleep and motivation. At the behavioral level, we are using optogenetics and receptor knockouts to investigate the function of specific cell populations in regulating waking and sleep states. Thus, we hope to advance our understanding of the biological underpinnings of sleep, arousal and their associated disorders..
Post Graduate Studies: 1988 - NIH Post-Doctoral Fellow, Dept. of Physiology & Biophysics, NYU Medical Ctr, NY (Rodolfo Llinás, mentor)
Graduate Degree: 1986 - Ph.D. Physiology & Biophysics
Graduate Degree Institution: New York University, NY
Undergraduate Institution: 1978 - B.S. (with Honors) Psychology, Northeastern University, Boston
- Ishibashi M, Gumenchuk I, Miyazaki K, Inoue T, Ross WN, Leonard CS.: Hypocretin/Orexin Peptides Alter Spike Encoding by Serotonergic Dorsal Raphe Neurons through Two Distinct Mechanisms That Increase the Late Afterhyperpolarization. (2016) Journal of Neuroscience, 2016 Sep 28;36(39):10097-115. doi: 10.1523/JNEUROSCI.0635-16.2016. Epub 2016 Sep 28.
- Ishibashi, M., Gumenchuk, I., Kang, B., Steger, C., Lynn, E., Molina, N. E., Eisenberg, L.M. and Leonard, C.S. : Orexin receptor activation generates gamma band input to cholinergic and serotonergic arousal system neurons and drives an intrinsic Ca(2+)-dependent resonance in LDT and PPT cholinergic neurons. (2015) Frontiers in Neurology, 6, 120. http://doi.org/10.3389/fneur.2015.00120
- Kohlmeier, K.A., Tyler, C.J., Kalogiannis, M., Ishibashi, M. Kristensen, M.P., Gumenchuk, I, Chemelli, R.M., Kisanuki, Y., Yanagisawa, M. and Leonard, C.S.: Differential actions of orexin receptors in brainstem cholinergic and monoaminergic neurons revealed by receptor knockouts: implications for orexinergic signaling in arousal and narcolepsy. (2013) Frontiers in Neuroscience. doi: 10.3389/fnins.2013.00246
- Leonard, C.S. and Kukkonen, J.P.: Orexin/hypocretin receptor signaling: A functional perspective. British Journal of Pharmacology, (2014) doi: 10.1111/bph.12296.
- Kohlmeier, K.A., Ishibashi, M, Wess, J., Bickford, M.E. and Leonard, C.S.: Knockouts reveal overlapping functions of M2 and M4 muscarinic receptors and evidence for a local glutamatergic circuit in the laterodorsal tegmental nucleus. Journal of Neurophysiology 108(10), 2751–2766. (2012) doi:10.1152/jn.01120.2011
- Kalogiannis, M., Hsu, E., Willie, J, Chemelli, R.M., Kisanuki, Y.Y., Yanagisawa, M. and Leonard, C.S.: Cholinergic modulation of narcoleptic attacks in double orexin receptor knockout mice. PLoS One 6(4): e18697. (2011) doi:10.1371/journal.pone.0018697.
- Ishibashi, M, Leonard, C.S. and Kohlmeier, K.A.: Nicotinic activation of laterodorsal tegmental neurons: implications for addiction to nicotine. Neuropsychophamacology 34, 2529–2547 (2009) doi 10.1038/npp.2009.82
- Huitron-Resendiz, S.*, Kristensen, M.P.*, Clark,S.D., Sánchez-Alavez, M., Tyler, C.J.,Nothacker, H-P., Civelli, O., Henriksen, S.J., Criado, J.R. Leonard, C.S. and de Lecea, L.: Urotensin II modulates REM sleep through activation of brainstem cholinergic neurons. Journal of Neuroscience, 25(23):5465-5474 (2005) *Equal contribution
- Goldberg, E.M., Watanabe, S., Chang, S., Leonard, C.S. and Rudy, B. Specific functions of synaptically-localized potassium channels in synaptic transmission at the neocortical GABAergic fast-spiking cell synapse. Journal of Neuroscience, 25(21):5230-5235 (2005)
- Willie, J.T., Chemelli, R.M., Sinton, C.M., Tokita, S., Williams, S.C., Kisanuki, Y., Marcus, J.N., Lee, C., Elmquist, J.K., Kohlmeier, K.A., Leonard, C.S., Richardson, J.A., Hammer, R.E., Yanagisawa, M.: Distinct narcolepsy syndromes in orexin receptor-2 and orexin null mice: Molecular genetic dissection of non-REM and REM regulatory processes. Neuron 38:715-730 (2003)
- Burlet, S., Tyler, C. J. and Leonard, C. S.: Direct and indirect excitation of laterodorsal tegmental neurons by Hypocretin/Orexin peptides: Implications for wakefulness and narcolepsy. Journal of Neuroscience 22(7): 2862-2872, 2002.
- Erisir, A., Lau, D., Rudy, B. and Leonard, C. S.: The function of specific K+ channels in sustained high frequency firing of fast-spiking neocortical interneurons. Journal of Neurophysiology; 82: 2476-2489, 1999.
See a complete bibliography for Christopher S. Leonard, Ph.D.