Bi/CNS 163

Bi/CNS 163

Final Exam

Handed out: 03-07-2000 @ noon

Due date: 03-14-2000 @ 7pm

Notes:

0. All the people in the group must work on all the problems.

1. There are two parts to this exam.

Part 1 (Fixed menu) consists of a series of textbook questions about sleep. If you paid attention during class, you may be able to answer these questions just without reading any additional material. Alternatively, you can check your notes, the web notes or any other textbooks or journals that you wish. The whole list of suggested books and papers can be found on the Bi/CNS163 web page.

Part 2 (a la carte) has 3 problems but you only have to choose 1 of these questions.

2. You will need to read some scientific papers to answer some of the questions. Be sure to allow yourself time to get, copy and read these papers.

3. Open books, papers, notes.

4. In groups of £ 4 people.

5. You can email an ascii/latex/word (97 or earlier) version of the final. Or you can put a hard copy in my mailbox (139-74) or office (BI 12B).

QUESTIONS? PROBLEMS?

Gabriel Kreiman

gabrielk@caltech.edu

626-395-2879

Caltech 139-74

1. Fixed menu

Answer ALL of the following questions:

a. One of the wrong ideas about sleep (but yet one of the most commonly held ones throughout history) is that sleep is a passive process, where the brain and body "rest and inactivate" and turned on again the next day. Mention at least two pieces of evidence that sleep constitutes an active mechanism and not a shutdown of the brain and body.

b. What happens with body and eye movements during the awake period, slow wave sleep and REM sleep?

c. Which biological species sleep and which ones don't?

d. Metion at least two different proposed functions for sleep and give two arguments for and against it for each.

e. Mention two areas that are activated with respect to the rest of the brain (as evidenced by PET studies or single-neuron electrophysiological studies) during REM sleep. Why do you think these areas are activated during REM sleep?

Suggested reading:

Hobson J. Sleep. New York. Scientific American Library. 1995

Horne J. Why we sleep: The functions of sleep in humans and other mammals. Oxford. Oxford University Press. 1988

See also the bibliography in the class web page www.cns.caltech.edu/~gabriel/sleep2000/bibliography.html

2. A la carte

Choose 1 of the following problems:

A. Patients with Fatal familial insomnia show a progressive decline in the amount of sleep. The pathology is characterized by hyperactivity, hypovigilance, attention deficits and thalamic degeneration. Patients end up dying.

i) Propose a scientific fact-based explanation for why the patients die.

ii) Suggest two experiments to test your theory.

(Be concrete both in the formulation of your hypothesis as well as in your suggested experiments. For example, if you claim that the subjects die because of the month in which they were born and the position of Jupiter at that time, you will not get a very high grade unless you can really prove it).

Suggested reading:

TATEISHI J, BROWN P, KITAMOTO T, et al.

FIRST EXPERIMENTAL TRANSMISSION OF FATAL FAMILIAL INSOMNIA
NATURE 376: (6539) 434-435 AUG 3 1995

COLLINGE J, PALMER MS, SIDLE KCL, et al.

TRANSMISSION OF FATAL FAMILIAL INSOMNIA TO LABORATORY-ANIMALS

LANCET 346: (8974) 569-570 AUG 26 1995

Zerr I, Giese A, Windl O, et al.

Phenotypic variability in fatal familial insomnia (D178N-129M) genotype

NEUROLOGY 51: (5) 1398-1405 NOV 1998

Lugaresi E, Tobler I, Gambetti P, et al.

The pathophysiology of fatal familial insomnia
BRAIN PATHOL 8: (3) 521-526 JUL 1998

Background suggested reading:

Prusiner S.B. Molecular biology of prion diseases. Science 252:1515-1522, (91)

Prusiner S.B. The prion diseases. Sci. Am. 30-37, (95)

Tobler I. and al, e. Altered circadian activity rhythms and sleep in mice devoid of prion protein. Nature 380:639-642, (96)

Tobler I., Deboer, T. and Fischer, M. Sleep and sleep regulation in normal and prion protein-deficient mice. J. Neurosci. 17:1869-1879, (97)

B. Sleep, exactly as we know it, does not occur in every animal (see your answer to the fixed menu questions). However, it is possible that some very related behaviors also take place in different animal species.

i) Mention at least two similarities between sleep and rest in lower animals.: Mention at least two differences between sleep and rest in lower animals.
iii) Read and criticize the paper by Hendricks et al on Neuron (see reference below).

Suggest at least two new experiments to further study the similarities and differences between rest and sleep in lower animals. Be specific, concrete and realistic about how the experiment would be run. An experiment stating that you will send 100 flies to Jupiter to observe whether they sleep there or not will not get a very high grade.

Suggested reading:
Hendricks JC, Finn SM, Panckeri KA, et al.
Rest in Drosophila is a sleep-like state
NEURON 25: (1) 129-138 JAN 2000
KAISER W, STEINERKAISER J: NEURONAL CORRELATES OF SLEEP, WAKEFULNESS AND AROUSAL IN A DIURNAL INSECT; NATURE 301: (5902) 707-709 1983
Background reading:

Evolution of sleep : stages of the formation of the 'wakefulness-sleep' cycle in vertebrates / Ida Gavrilovna Karmanova ; translation from Russian by A.I. Koryushkin and O.P. Uchastkin with editorial assistance by Werner P. Koella Basel ; New York : Karger, c1982


C. Daniel Margoliash (ex-Caltech) published recently a nice experiment suggesting that birds learn new songs while they sleep (see reference below).
Read and criticize the paper by Margoliash (see reference below).

How would you design an experiment to addressed the problems you raised in the previous question? Be specific, concrete and realistic about how the experiment would be run. An experiment suggesting that you will teach birds how to sing songs from the Beatles at 4 am will not get a very high grade.

Mention at least two pieces of evidence that learning/memory related processes may occur duing sleep in rats or mice.

Some researchers have suggested that neurogenesis (formation of new neurons) or recuitment of new neurons is a requirement for song learning (see references by Nottebohm). Assuming for this question that this is proved, suggest an experiment to test whether there is any relationship between sleep and the process of neurogenesis or neuronal recruitment.

Suggested reading: