Integrators of Physiological Functions

  • Luis de Lecea
  • J. Gregor Sutcliffe

Table of contents

  1. Front Matter
    Pages i-xxiii
  2. Discovery of the Hypocretins/Orexins and Their Receptors

    1. Front Matter
      Pages 1-1
    2. Luis de Lecea, J. Gregor Sutcliffe
      Pages 3-11
    3. Takeshi Sakurai
      Pages 13-23
  3. Animal Models in the Study of the Hypocretinergic System

    1. Front Matter
      Pages 25-25
    2. Takeshi Sakurai, Masashi Yanagisawa, Michihiro Mieda
      Pages 27-38
    3. Seiji Nishino
      Pages 39-58
  4. Detailed Anatomy of the Hypocretinergic System and Related Hypothalamic Circuits

    1. Front Matter
      Pages 59-59
    2. Teresa L. Steininger, Thomas S. Kilduff
      Pages 61-75
    3. Tamas L. Horvath
      Pages 77-93
  5. Physiological Consequences of Hypocretin Activation

    1. Front Matter
      Pages 121-121
    2. Anthony N. van den Pol
      Pages 123-136
    3. Gary Aston-Jones, J. Patrick Card, Yan Zhu, Mónica González, Elizabeth Haggerty
      Pages 137-152
    4. Christopher S. Leonard, Christopher J. Tyler, Sophie Burlet, Shigeo Watanabe, Kristi A. Kohlmeier
      Pages 153-168
    5. Oliver Selbach, Helmut L. Haas
      Pages 169-189
    6. Evelyn K. Lambe, George K. Aghajanian
      Pages 191-202
  6. Pharmacology of the Hypocretins and Drug Design

    1. Front Matter
      Pages 203-203
    2. Jyrki P. Kukkonen, Karl E. O. Åkerman
      Pages 221-231
  7. The Hypocretins in Narcolepsy and Arousal

    1. Front Matter
      Pages 233-233
    2. Wynne Chen, Jamie M. Zeitzer, Emmanuel Mignot
      Pages 235-254
    3. Patrice Bourgin, Yves Dauvilliers
      Pages 263-277
    4. Gert Jan Lammers, Sebastiaan Overeem
      Pages 279-290
    5. Barbara E. Jones, Michel Muhlethaler
      Pages 291-303
  8. The Hypocretins in Feeding and Energy Balance

    1. Front Matter
      Pages 305-305
    2. Katherine E. Wortley, Sarah F. Leibowitz
      Pages 307-314
  9. The Hypocretins in Addiction and Hyperarousal

    1. Front Matter
      Pages 315-315
    2. Benjamin Boutrel, Paul J. Kenny, Athina Markou, George F. Koob
      Pages 317-326
    3. Ralph J. DiLeone
      Pages 327-337
    4. Ariel Y. Deutch, Jim Fadel, Michael Bubser
      Pages 339-351
    5. Craig W. Berridge, Rodrigo A. España
      Pages 353-367
  10. Role of Hypocretins on Peripheral Systems

    1. Front Matter
      Pages 369-369
    2. Willis K. Samson, Meghan M. Taylor, Alastair V. Ferguson
      Pages 371-383
    3. Annette L Kirchgessner, Erik Näslund
      Pages 385-393
    4. Miguel López, Manuel Tena-Sempere, Tomás García-Caballero, Rosa Señarís, Carlos Diéguez
      Pages 395-423
    5. Tetsuro Shirasaka, Hiroshi Kannan
      Pages 425-435
  11. Back Matter
    Pages 437-441

About this book


The first report that rapid eye movements occur in sleep in humans was published in 1953. The research journey from this point to the realization that sleep consists of two entirely independent states of being (eventually labeled REM sleep and non-REM sleep) was convoluted, but by 1960 the fundamental duality of sleep was well established including the description of REM sleep in cats associated with “wide awake” EEG patterns and EMG suppression. The first report linking REM sleep to a pathology occurred in 1961 and a clear association of sleep onset REM periods, cataplexy, hypnagogic hallucinations and sleep paralysis was fully established by 1966. When a naïve individual happens to observe a full-blown cataplexy attack, it is both dramatic and unnerving. Usually the observer assumes that the loss of muscle tone represents syncope or seizure. In order to educate health professionals and the general public, Christian Guilleminault and I made movies of full-blown cataplectic episodes (not an easy task). We showed these movies of cataplexy attacks to a number of professional audiences, and were eventually rewarded with the report of a similar abrupt loss of muscle tone in a dog. We were able to bring the dog to Stanford University and with this as the trigger, we were able to develop the Stanford Canine Narcolepsy Colony. Breeding studies revealed the genetic determinants of canine narcolepsy, an autosomal recessive gene we termed canarc1. Emmanuel Mignot took over the colony in 1986 and began sequencing DNA, finally isolating canarc1 in 1999.


Hypocretins Integrators Physiological anatomy brain hormone metabolism neurons

Editors and affiliations

  • Luis de Lecea
    • 1
  • J. Gregor Sutcliffe
    • 1
  1. 1.The Scripps Research InstituteLa JollaUSA

Bibliographic information