Neuroscience Graduate Group

Pathophysiology of Sleep and Sleep Disorders

Thursdays 10/23/08-12/4/08 2:30-5:30 pm except for the Thanksgiving week, when we will meet on Tuesday 11/25.

Course Summary

This is a 7-week seminar course where literature involving the neurobiology of sleep and sleep disorders will be discussed. The format will consist of a round table discussion of 4-7 primary papers, distributed to students the previous week. Each session will begin with a 10-30 minute introductory lecture by a either Drs Pack or Raizen or by another member of the faculty with relevant expertise. This will be followed by discussion of the papers, which will be led by the students with faculty input.
The goals of this course are:
  1. To teach students some of the outstanding questions in sleep science and sleep medicine.
  2. To guide students through the reading of influential papers in the sleep research field.
  3. To introduce students to some of the methodological approaches in sleep science. To learn the relative merits and weaknesses of various approaches.
  4. To help student gain an appreciation for the difference between circadian rhythms and sleep and the overlapping roles of genes in circadian and sleep regulation.

The course will be opened to post docs, fellows and advanced undergraduate students in addition to graduate students. Students or post-docs who audit the course with the instructors' permission are required to read all the papers and to participate in the discussion. i.e. expectation of auditors will be no different from expectation of credit students.

FACULTY: Along with Dr. David Raizen and Dr. Allan Pack, other faculty with expertise relevant to the topic under discussion will be invited to specific classes.

REQUIREMENTS AND GRADING: Students will be graded on attendance and participation in the discussion. Each student will be expected to read all assigned papers each week and in addition will prepare and then lead a detailed discussion on one of these papers. Papers should be read critically and should be approached as one approaches a journal club paper. While in general, papers under discussion will be scientifically sound and carry important conclusions, one should critically read all aspects of the papers including methods, results, the writing, and the conclusions. Some background reading may be required to fully understand some of the papers. Course instructors will be available to help if questions arise while reading the papers during the week before class.

Course Sessions - Fall 2008

Topic Additional Faculty Date Papers (preliminary list)
Overview of sleep disorders and Sleep Regulation: Phenomenology Maislin 10/23 1. Borbely: The 2-process model
2. Franken et al J. Neurosci 2001: Process S buildup in mice
3. Tobler: Mice lacking SCN still have homeostatic regulation.
4. Dijk and Czeisler: Forced desynchony and constant routine to study circadian and homeostatic regulation of human sleep.
5. Van Dongen et al Sleep 2003: using chronic partial sleep deprivation to challenge 2-process model.
6. Kim et al and Turek PNAS '07: using chronic partial sleep deprivation to challenge 2-process model; allostasis
Sleep regulation 1: Circuitry Veasey 10/30 c-fos staining:
1. Saper: ID of VLPO using c-fos
2. Shiromani: lesion paper calling into question individual wake-promoting nuclei.
3. Aston-Jones paper showing role of locus coeruleus in vigilance.
4. Paper mapping projections of HCRT neurons.
5. De Lecea paper Nature paper showing optogenetic control of arousal
Sleep regulation 2: Signal transduction pathways and molecules TBA 11/6 EGF signaling
1. Kramer et al, Science '01: EGF in mouse sleep/quiescence
2. Foltenyi et al, Nature Neurosci '07: EGF in fly sleep.
3. Van Buskirk, Nature Neurosci '07: EGF in worm Quiesc.
cAMP and adenosine signaling
4. Hendricks et al, Nature Neurosci '01: cAMP in flies.
5. Graves and Abel, J. Neurophys '03: CREB in mice.
6. Porka-Heiskanen and McCarley Science '97: adenosine in basal forebrain
Circadian regulation and circadian sleep disorders Sehgal 11/13 1. Konopka and Benzer ('71)
2. Takahashi cloning of CLOCK.
3. Ptacek Cell paper modeling FASPS in mice, Cell '07
4. McNight science paper on NPAS2 or Saper recent paper on DMH clock role in restricted feeding clock.
5. A paper on the role of clock genes in sleep homeostasis? Perhaps a paper on cry-1,2.
Sleep Function Frank 11/20 or 11/18 (Society for Neuroscience meeting) 1. Rechschtaffen et al, Sleep '02: review of sleep deprivation experiments in rat.
2. Tu and McNight Logic of Yeast Metabolic Cycle.
3. Frank review on the purpose of sleep
4. Stickgold implicit learning in humans paper
5. Frank Neuron '02: kitten ocular dominance columns?
6. Cirelli and Tononi: Nature Neurosci paper supporting synaptic homeostasis model
Narcolepsy and Restless Leg Syndrome Cantor 11/25 1. Mignot 8/99 Cell paper.
2. Yanigasawa 8/99 Cell paper.
3. Mignot low CSF hypocretin paper.
4. Restless Leg Syndrome iron autopsy study in Neurology
5. Winkelmann RLS GWA study '07.
Sleep Deprivation Naidoo 12/4 1. Neurocognitive consequences of sleep deprivation?
2. Meta-analysis of studies looking at relationship between total sleep time and obesity/diabetes (Sleep April '08)
3. Van Cauter Lancet '99: Endocrinological consequences of acute sleep deprivation.
4. Cirelli and Tononi study in rat showing evidence of ER stress, plasticity, etc during wakefulness, and perhaps synaptic down scaling during sleep.