NBIO 75b - Neurobiology of Stress
Course Introduction: All organisms experience stress - from nematodes facing nutrient deprivation to humans studying for final exams. The stress response is a highly dynamic process which sometimes results in increased cognitive function (for example, needing to be just a little stressed out to write that final paper) but can also result in profound deficits and even contribute to neuropsychiatric diseases, such as anxiety disorders and PTSD. This course will provide a comprehensive survey of the neurobiology of stress by taking a molecules-to-organisms approach with such topics as hormone action in the brain, neuronal morphology and connectivity, learning and memory, sex differences in stress responsivity, and stress-related human disorders.
Instructors: Sarah Richards and Daniel Powell
Email: srichard@brandeis and
Office Location and Hours: Office hours will be held in Volen 301 on Monday at 1pm (Dan) and Thursdays at 3:30pm (Sarah), or by appointment.
Communication: All communication for this course will be made through the Latte class mailing list. Specific questions can be addressed to either instructor via email.
Prerequisites: NBIO 140b or BIOL 42a
Course Materials: Course readings will consist of readings from the assigned textbook as well as primary literature articles and literature review articles. All articles from the primary literature will be available on Latte. The required textbook is:
George Fink. Stress: neuroendocrinology and neurobiology. Handbook of stress, volume 2. Elsevier, 2017
Learning Goals: Students will gain experience with reading primary literature and oral presentation skills through extensive in-class discussion of this material and a final poster presentation. Students will also develop written scientific communication skills through three writing assignments requiring mastery of scientific literature. The neurobiology of stress presents a unique opportunity to explore the interactions among complex biological systems, the endocrine and nervous system, to develop a more holistic view of brain/body interactions.
Course Format: Class time will primarily be divided between short lectures (about 30 minutes) and longer instructor-facilitated discussions of course readings, including primary literature articles, review articles, and textbook readings.
Example Class:
(35 minutes) Discussion: Facilitated discussion of assigned readings
(5 minutes) Transition: Last minute questions and break before lecture
(35 minutes) Lecture: Introduction to new material for discussion next class
(5 minutes) Wrap-Up: Reminders of upcoming assignments, last-minute questions
Evaluation: Students are expected to work toward mastery of course readings and demonstrate their knowledge through both written and oral communication. No late assignments will be accepted without documented extenuating circumstances.
In class Discussion: Students will primarily be assessed on thoughtful discussion of course readings during in-class discussions. In these discussions, students will be assessed on effort to master course readings, engagement with the material, and critical thinking. Participation in these discussions is essential for success in the course. Students will be scored on attendance (1pt) and contribution to discussion (1pt) for each class period. For classes without a discussion component, scoring will be based on attendance alone (2pts).
Writing Assignments: Students will prepare two papers (between 1500 and 2500 words each) that focus on comprehension of and critical thinking about primary research articles.
The first assignment asks students to choose a review article from the course readings and research work being completed in the author’s lab within 5 years after the review was published. Students will summarize the lab’s current work and reflect on the connection of this work to the review article. For example, students may focus on whether this work supports the data in the chosen review, refutes that data, or takes a new direction entirely. Assessment will be based on understanding of the review article (6pts), comprehensive review of the labs current work (6pts), commentary on that work (6pts), writing quality (6pts) and appropriate corrections from the first draft (6pts). The second assignment focuses on learning to summarize and critique a peer-reviewed journal article. Students will choose one article from a curated list of 2-3 recent articles and compose a paper that is approximately ⅓ summary of that work and and ⅔ analysis, including critique of the data and conclusions. Assessment will be based on accurate summary (6pts), relevant critique (6pts), use of outside sources (6pts), writing quality (6pts), and appropriate corrections from the first draft (6pts).
For each writing assignment, students will be given the opportunity to revise their work to address instructor comments. Final grades will be assigned based on both the submitted draft and re-submitted papers.
Pre-Discussion Questions: Prior to each in-class discussion, students will have the opportunity to submit responses to five pre-discussion questions. The purpose of these questions is to help students reflect on their understanding of the material, prepare to participate in discussion, and highlight any difficult portions of the reading. Responses will be used to help facilitate the in-class discussion and make sure that students are able get help with any difficult material - even if they don’t feel comfortable asking a particular question in class. Students must complete 15 assignments (4pts each) by 6am on the day of the discussion to get full credit for this portion of the course. Assessment will be based on completion.
Final Presentations: Each student will select one area of study within the stress field and prepare a poster presentation focusing on a recent finding in that field. Students will be expected to synthesize knowledge from several primary sources to give context to the article(s) that they use as a basis for their poster. Posters are expected to include an introduction, a succinct summary of the findings, analysis of the methods and conclusions, and ideas for future directions. Before each student presents, they are expected to participate in an in-class workshop day, during which peers and instructors review posters and offer suggestions. Generally, grades will be assessed based on understanding of the material, use of outside sources, feasible future directions, presentation quality, readability of final poster, and participation in the workshop day. Detailed rubrics will be provided well in advance of the presentations and workshop day.
Summary:
Activity / Points / % TotalIn-Class Discussion / 100 (4pts X 25 days) / 25%
Writing Assignments / 60 (30pts X 2 papers) / 15%
Pre-Discussion Questions / 60(4pts X 15 responses) / 15%
Poster Presentations / 180* / 45%
Total / 200 / 100%
*see written description
Outside of Class: Success in this four-credit course is based on the expectation that students will spend a minimum of 9 hours of study time per week in preparation for class (readings, papers, discussion sections, preparation for exams, etc.).
Disabilities: If you are a student with a documented disability on record at Brandeis University and wish to have a reasonable accommodation made for you in this class, please contact either Sarah or Daniel immediately.
Academic Integrity: Collaboration is incredibly important when learning new and difficult material and we encourage students to work together whenever possible. However, each student is required to submit written assignments that have been independently created and include proper citations for all sources. Please ask your instructors if you are unsure of how to cite a source appropriately or consult the LTS - Library Guides: Academic integrity is of the utmost importance in this course and we encourage students to review the Brandeis Rights and Responsibilities document ( before completing assignments. Any cases of academic dishonesty will be taken seriously and forwarded to the Director of Academic Integrity.
Course Plan
Introduction to Stress and Background Information
Jan 11 – Course introduction – Course structure, Syllabus overview, and Brief Introduction
●What is stress?
●Introduction to autonomic nervous system (sympathetic/parasympathetic) and relevant organ systems.
For Next Class:
●Chapter 17 from textbook
●Review information about action potentials and synaptic transmission from Principles of Neuroscience
●YouTube video:
●Optional resource: Goldstein 2010 (Adrenal response to stress, general overview)
Jan 16 – Autonomic Nervous System - Sympathetic and Parasympathetic Activation
●Introduce anatomical and chemical underpinnings of these two systems
●Fast and slow transmission in the ANS – fast synaptic transmission, medium to fast modulation, slow hormone release/endocrine system
●Introduce time scales of responses, both time of signal release/reception and duration of response vs signal molecule presence.
●Discussion: How do people view stress on a biological level?
For Next Class:
●Read p. 99 - 110 of Principles of Neurobiology, Lou text
●Bockaert 2006 (Review of 5HT receptors and metabotropic pathways)
Jan 23 – Homeostasis - From synapses to organisms
●What is neurotransmission and how does it work?
●How synaptic transmission is terminated - reuptake, degradation, and recycling.
●What is homeostasis and how does it work at the cellular and systems levels?
●How does homeostasis relate to stress and why is it critical for organism fitness?
●Discussion: Metabotropic signaling, hormonal signaling, and Experimental results
For Next Class:
●McEwen 2011 (Stress- And Allostasis- Induced Brain Plasticity)
●Ch. 20 (pg. 214-216 only) from textbook subsection “Allostatic Load Models”
●Turrigiano and Nelson 2004 (Homeostasis)
Hormones, Neurotransmitters, and Stress
Jan 25 – Environment to Periphery - Cortisol, glucocorticoids, and the HPA axis
●How does information about stressful stimuli enter the body?
●Introduce immediate and long-term peripheral responses to stress.
●Introduce peripheral structures that underlie the stress response.
●Discussion: How does ability to maintain homeostasis increase fitness?
For Next Class:
●Smith and Vale 2006 Review Article (Autonomic Nervous System)
●Spencer and Deak 2017 (HPA axis in multiple biological systems)
●Chapters 8 and 10 from the textbook
Jan 30 – Periphery to the Brain - Cortisol, glucocorticoids, and the HPA axis (cont.)
●How do peripheral stress responses impact the brain?
●Introduce periphery-to-brain circuitry.
●Establish importance of brain-body interaction.
●Discussion: How does the peripheral stress response relate to your perception of stress?
For Next Class:
●Chapter 19, subsection “Stressors, Glucocorticoids, and the HPA Axis” pg 198-200
●de Kloet et al. 2005 (Stress Response in Brain and Body)
●McEwen 2008 (Central Actions of Stress Hormones)
Feb 1 – Catecholamine Neurotransmitters and their Cellular Actions - Epinephrine, Norepinephrine, and Acetylcholine
●Establish the basic biochemical properties of epinephrine and norepinephrine
●Introduce basic cellular actions and receptor types
●Discussion: Understanding stress through the lens of brain/body interaction
For Next Class:
●Marder & Thirumalai 2002 (Cellular, synaptic and network effects of neuromodulation)
●Marder 2012 (Neuromodulation of neural circuits: Back to the Future)
Feb 6 – Monoamine Neurotransmitters and their Cellular Actions - Dopamine and Serotonin
●Establish the basic biochemical properties of dopamine and serotonin
●Introduce the basic cellular actions and receptor types. [1]
●Build a foundation for the actions of these molecules in the brain, going beyond pop science understanding of “happiness molecules”
●Discussion: Hormones and the brain - combining what we’ve learned so far.
For Next Class:
●Harris-Warrick & Marder 1991 (Modulation of neural networks for behavior)
●Chapter 7 of textbook
●Lucas et al. 2004 (Social Stress and Dopamine)
Feb 8 – Stress Responsive Circuits in the Brain - The Limbic System
●What is the limbic system and what does it do?
●Why is it stress responsive? - receptors and neurotransmitter systems
●Discussion: Complex actions of monoamines in the brain and why there isn’t a “happiness pill”
●First Writing Assignment
For Next Class:
●Herman et al. 2005 (Limbic system mechanisms of stress regulation: HPA)
●McEwen and Milner 2007 (Hippocampus, Stress, and Sex)
Feb 13 – Stress Responsive Circuits in the Brain - The Prefrontal Cortex
●What is the prefrontal cortex and do rodents even have one?
●How does the cortex respond to stress?
●Discussion: What kinds of pathology could result from stress-induced alteration of limbic function?
For Next Class:
●Cook and Wellman 2004 (Chronic stress alters dendritic morphology in rat medial prefrontal cortex)
●Arnsten 2009 Review (Stress signaling pathways that impair prefrontal cortex structure and function)
Stress Effects on Brain and Behavior
Feb 15 – Why zebras don’t get ulcers (and why humans do) - Acute vs Chronic Stress
●Introduce major differences between acute and chronic stress responses at the cellular level.
●Refine understanding of different types of stressors.
●How do we model acute and chronic stress in the lab?
●Discussion: How could prefrontal function be disrupted by stress? What might the outcome be?
●First Writing Assignment: First Drafts Due
For Next Class:
●Chapter 8 from textbook
●Seib and Wellman 2003 (Mild Chronic Stress)
●Yuen et al. 2009 (Acute Stress and Working Memory)
Feb 20 – No Class
Feb 22 – No Class
Feb 27 – Studying Stress in the Lab - Animal models of stress
●What are common assays used to measure stress?
●What are some common stress-induced changes and what do they mean?
●Are there behaviors that are related to stress in animal models?
●Discussion: How does the acute or chronic nature of stress impact the outcome for the organism?
●First Writing Assignment: Drafts Handed Back
For Next Class:
●Liston et al. 2006 (Stress Effects on Morphology and Behavior)[2]
●Radley et al. 2005 (Recovery after Stress in prefrontal cortex)
●Review Ch. 19 information about rodent models in stress research.
Mar 1 – Stress Effects on Behavior - Learning and memory
●Revisit tasks used to assess learning and memory in rodents.
●Introduce basic stress-induced changes in learning and memory circuits
●Revisit acute vs. chronic stress.
●Discussion: How are stress-related behaviors in the rodent ecologically relevant? How do circuit-level changes alter an organism's behavior?
For Next Class:
●Chapter 31 of textbook
●Vyas et al 2002 (Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons)
●Magarinos and McEwen 1995 (Stress induced atrophy of apical dendrites of CA3 neurons)
●Luine et al 1994 (Repeated stress causes reversible impairment of spatial memory performance)
Mar 6 – Stress Effects on Behavior - Behaviors that involve the Prefrontal Cortex and Amygdala
●Introduce fear learning circuitry and fear extinction paradigms
●Introduce multiple roles of the prefrontal cortex in modulating fear behaviors.
●Discussion: How does rodent stress relate to human stress? How do circuit-level changes alter an organism's behavior?
For Next Class:
●Mitra et al. 2005 (Stress Duration and the Amygdala)
●Erlich et al. 2012 (Fear Conditioning and the Lateral Amygdala)
●Liston et al. 2006 (Prefrontal Cortex Morphology and Set-Shifting)
●Chapter 9 from textbook
Mar 8 – Sex Differences in Stress Outcomes - Learning and Behavior
●Establish basic behavioral differences among males and females in common assays.
●Introduce fundamental differences in stress-response at the behavioral level between males and females
●Explore differences in recovery from stress in males and females
●Discussion: How do cortical and limbic systems interact during the stress response and what does this mean for the organism?
●First Writing Assignment: Final Drafts Due
For Next Class:
●Mazid et al. 2016 (M v. F hippocampal differences, chronic v. acute stress)
●Shors et al. 2001 (M v F spine density, acute v. chronic stress)
●Farrell et al. 2013 (Sex Differences in Dendritic Complexity)
●Chapter 32 from textbook (Ch.13 optional)
Mar 13 – Sex Differences - Cellular Basis for Sex-Dependent Stress Responses
●How does estrogen sensitivity alter neuronal function?
●How does the distribution of estrogen receptors alter stress responsivity?
●Introduce role of estrous cycle in stress outcomes.
●Discussion: What are the overall implications of sex and stress for behavior?
●Second Writing Assignment
For Next Class:
●Catherine Woolley 2006 Review (Acute effects of estrogen on neuronal physiology)
●Williams et al 2011 (Ovarian hormones influence CRFR colocalization with d-opioid receptor in CA1 pyramidal cell dendrites)[3]
●
Mar 15 – Parental and Early Life Stress - Outcomes for Offspring Fitness
●Describe basic parental care behaviors
●Introduce stress-induced changes in these behaviors.
●Introduce the idea of transgenerational impact of stress.
●Discussion: What is the neuronal basis of sex differences in stress responsivity?
For Next Class:
●Champagne and Meaney 2006 (Gestational Stress and Offspring Development)
●Pruessner et al. 2004 (Dopamine Release and Early LIfe Care in Humans)
●Chapter 18 and 19 from textbook
Interactions of Stress and Disease
Mar 20 – Predisposition to Stress Disorders - Genetic and Environmental Risks
●Introduce animal models for altered stress responsivity
●Introduce common polymorphisms that lead alter stress response in humans
●Introduce comorbidity with other psychopathology.
●Discussion: How does parental fitness relate to offspring outcome? What does this mean for humans?
●Second Writing Assignment: First Draft Due
For Next Class:
●Saavedra-Rodriguez et al. 2013 (Chronic Social Instability and Anxiety)
●Camp et al. 2012 (Strain Differences in Stress Response)
●Please review the basics of epigenetics by reading Golbabapour et al. 2011 or a textbook from a previous course.
Mar 22 – Predisposition to Stress Disorders - Epigenetics
●What is epigenetics?
●What are common epigenetic modifications associated with stress?
●Is there any possibility for recovery:
●Discussion: Is resistance to stress-induced changes always a good thing? What purpose does stress serve in an organism's fitness?
For Next Class:
●Hunter et al. 2015 (Review of Stress and the Transcriptome Modification)
●Vargas-Lopez et al. 2016 (Histone Deacetylase Inhibition and Spatial Memory)
●Chapter 11 and 12 from textbook
Mar 27 –Stress and sleep
●Why is sleep important?
●What happens to cortisol levels during sleep?
●What is the interaction between stress and sleep loss?
●Discussion: How do life experiences, such as stress, impact the brain?
●Second Writing Assignment: Drafts handed back
For Next Class:
●Steiger 2002 Review (HPA and sleep)[4]
●LeProulet 1997 (Sleep Loss)
●Liston et al. 2013 (Circadian rhythms, stress, and learning)