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NSC 312: Seminar in Neuroscience: General Anesthesia, Spring 2011


Meetings: Tuesday 1.00-2.50pm
Instructor: Adam Hall: x3467, Ford Hall 202A, ahall@smith.edu
Office Hours: Friday 3-4pm, or by appointment.

 



Course Description:

This seminar will explore the history of general anesthesia, current anesthetic practices and primarily focus on the molecular mechanisms of anesthetic actions in the mammalian brain. Prerequisite: either BIO 202, 200, 300 or 310. Enrollment limited to 12. 4 credits.


Syllabus

 

Jan 25th Pharmacology of General Anesthesia
   
Feb 8th History of Anesthesia and Anesthetic Practice, Surgery suite tour
   
Feb 15th Meyer-Overton, MAC and the Protein-Lipid Debate
   
March 1st Intro to modulation of ion channels by volatiles
   
March 8th Anesthetic modulation of voltage-gated channels
Presentation #1+2
   
March 15th SPRING RECESS
   
March 22nd Modulation of excitatory ligand-gated ion channels
Presentation #3+4
   
March 29th Anesthetic action at postsynaptic GABAA receptors
Presentation #5+6
   
April 5th Field trip to Boston to visit Mt. Auburn Cemetery and Mass. Gen. Hosp
   
April 12th Long-term effects of anesthetics, toxicity and pre-conditioning
   
April 19th ACH away at BNA meeting
   
April 26th Term Paper presentations
   

 

Assigned Readings

Feb 1st
(1) The Development of Concepts of Mechanisms of Anesthesia, Chapter 1, Neural Mechanisms of Anesthesia, D. Caton and Antognini, (2003).

(2) “ Clinical Anesthesia and Practice” Kirby et al. Chapter 30, Pharmacologic Considerations and anesthetic administration, Volckmar & Eckenhoff

(3)“ Clinical Anesthesia and Practice” Kirby et al. Chapter 33, Intravenous Anesthetic Agents, Rogers

(4) “ Clinical Anesthesia and Practice” Kirby et al. Chapter 34, Inhalation Agents, Seropian, & Stevens

Feb 8th
(1) Ether Day , J.M. Fenster, (2002).

Feb 22th
(1) “Basic Pharmacology of volatile anesthetics” Chapter 1, J.P. Dilger in ‘Molecular Bases of Anesthesia’ Moody and Skolnick, (2001).

March 1st (1) Chapters 11, 12 and 13 of “Essentials of neural science and behavior” Kandel, Schwartz and Jessell (only if requiring this background).

(2) “ Which molecular targets are most relevant to general anesthesia?” N.P. Franks and W. Lieb, Toxicology Letters, 100-101, 1-8 (1998).

(3) Molecular and cellular mechanisms of general anesthesia, N.P. Franks and W. Lieb, Nature, 367, 607-614 (1994).

(4) General anesthetic actions on ligand-gated ion channels, M. Krasowski and N. Harrison, Cellular and Molecular Life Sciences, 55, 1278-1303, (1999).


March 8th
(1) ‘Volatile anesthetics significantly suppress central and peripheral mammalian sodium channels’, D.S. Duch, B. Rehberg, T.N. Vysotskaya, Toxicology Letters, 100-101, 255-263 (1998)

(2) ‘ Volatile anesthetic effects on Calcium Channels’ H.C. Hemmings, Chapter 6 in ‘Molecular Bases of Anesthesia’ Moody and Skolnick, (2001).

March 22th
(1) ‘Volatile anesthetic effects at excitatory amino acid receptors’ J.E. Dildy-Mayfield and R.A. Harris, Chapter 9 in ‘Molecular Bases of Anesthesia’ Moody and Skolnick, (2001).

(2) ‘Effects of volatile anesthetics at nicotinic acetylcholine receptors’ P. Flood, Chapter 13 in ‘Molecular Bases of Anesthesia’ Moody and Skolnick, (2001).


March 29th
(1) ‘Effects of volatile anesthetics on GABAA receptors: electrophysiologic studies’ R.A. Pearce, Chapter 10 in ‘Molecular Bases of Anesthesia’ Moody and Skolnick, (2001).

April 12th
(1) Inhalational anesthetics as preconditioning agents in ischemic brain. Wang et al., 2008, Current Opinion in Pharmacology 8, 104-110

(2) General Anesthetics and long-term neurotoxicity, M. Perouansky from ‘Modern Anesthetics’ Handbook of Experimental Pharmacology.

 

Assignments

1) History of anesthesia essay: “Who discovered general anesthesia?” (10%)
2) Presentations in pairs (20%)
3) Annotated Bibliography (10%)
4) Term paper on the molecular basis of anesthetic action in the brain (30%)
5) Term Paper Presentation (10%)
6) Class participation (20%)

HISTORY OF ANESTHESIA ESSAYAfter our discussion of the key players in the discovery of anesthesia, and after reading ‘Ether Day’ by Julie Fenster, write a short essay (3 page maximum) entitled “Who discovered general anesthesia?”. You must decide which historical character you determine was the most influential in introducing general anesthetics into surgical practice. Back up your selection with arguments highlighting their input and the impact it had on the medical and scientific communities. Due on Feb 15th in class.

ARTICLE PRESENTATION After reading background reviews (see assigned reading) and after consultation with AH, pairs will select one article (primary literature only) to present. This presentation should be ~15-20 minutes in length and consist of an in depth explanation of the primary literature article. Give a brief background and explain the methodology as needed to interpret the experiments. Then discuss how the knowledge gained elucidates some aspect of anesthetic action in the mammalian brain. This is a Powerpoint presentation with handouts as needed to clarify the material. Please email AH the Powerpoint slides by 5 p.m the Monday before your presentation.

ANNOTATED BIBLIOGRAPHY
An annotated bibliography is a combination of the complete bibliographic citation along with several sentences (5-10) of concise summary of that article IN YOUR OWN WORDS. This usually includes the most important results and the relevance of the study to the field. The articles you choose will be ones that you are using or have considered for use in your term paper. You should have 5 - 10 references of primary literature in your annotated bibliography. Any reviews cited do not require annotation. Due on Apr 5th in class.

TERM PAPER Choose a class of neuronal molecules (e.g. a receptor type, an ion channel, an enzyme involved in a second messenger cascade) that you know to be affected by the action of general anesthetics. Your term paper will explore how general anesthetics modulate the activity of your chosen class of molecules and how this modulation may explain some aspect of anesthesia (e.g. hypnosis, loss of consciousness, amnesia, emesis) in the mammalian brain. The paper should draw largely from the primary literature, comparing and contrasting the views of researchers in the field.

Coverage: Your discussion of an anesthetic mechanism should include:

1. An abstract of no more than 150 words as the opening page.

2. Definitions of the key molecules (e.g. receptors, channels) involved

3. A brief historical perspective and discussion of the development of our changes in understanding of the role of these molecules in anesthesia.

4. In your own words, a synthesis of the primary literature pertaining to your chosen anesthetic mechanism, comparing and contrasting all the relevant articles.

5. A brief overview of the net effects on the nervous system (e.g. behavioural changes) resulting from the anesthetic modulation of the molecules that you have chosen to study.

Documentation: The use of proper and complete referencing and documentation is important. The references cited should be given in the format given below. Be sure to include all authors. Author, A. B. (complete listing of all authors), Year, Title of the article. Abbreviated Journal Title, Vol.: Complete Pagination.


For example:
Duch, D.S., Rehberg, B., Vysotskaya, T.N. 1998, Volatile anesthetics significantly suppress central and peripheral mammalian sodium channels, Toxicol. Lett., 100-101, 255-263.

Franks, N.P. and Lieb W.R., 1998, Which molecular targets are most relevant to general anesthesia? Toxicol. Lett., 100-101, 1-8.

Within the body of the paper, please refer to the references by author and year within parentheses. For example, this syllabus was prepared at Smith College (Hall, 2009). It has been demonstrated that isoflurane affects GABAA receptors stereoselectively (Hall et al., 1994). Hall et al., (1994) established that the modulation of GABAA receptors by isoflurane was stereoselective…. If you have any questions, please feel free to consult AH.

Optional Draft due: Apr 12th 5.00pm
Completed paper deadline: April 29th Fri by 4.00pm

Format: The paper should be typed on white paper, double-spaced, 12 pitch Times-Roman, paginated and up to 10 pages in length (exclusive of figures and bibliography).

 

TERM PAPER PRESENTATION
This short presentation (maximum of 5 minutes) will consist of a summary describing your chosen molecular mechanism of anesthetic action including reference to the net effects on the mammalian nervous system. No more than five Powerpoint slides may be used. Please email AH the Powerpoint slides on the Monday before the presentation.

FIELD TRIP
There will be a field trip to Massachusetts General Hospital and Mount Auburn Cemetery, Cambridge, MA. We will be traveling in Smith College vans, leaving promptly at 12:00 from Smith to arrive at MGH by 2 pm., then departing around 4pm to return to Smith at approximately 6 pm.

DEADLINES
All work is due on the designated day. If work is handed in late, 5% will be deducted from the grade per day beyond the deadline.

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