Study  guides  and  introductions  to  

Our course management software does not permit a return to an assignment once you have
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assignments, learning objectives, etc. are no longer accessible. This document reproduces all of
that information in the order in which the assignments are due.

Electricity  1  
To understand how neurons generate, conduct, and transmit signals you will need a good
command of basic electricity. This survey of ten questions addresses common misconceptions
about electricity, electric current, charge carriers, conductors, etc.
No grade will be recorded for this exercise. When you complete Electricity 1 you will
immediately have access to feedback. You may repeat this assessment as many times as you
Note bene – Some of these questions would give a physics major a hard time. They did so for
me. All the same, when you read the feedback the correct answers should make sense.
Introduction to the study guides
Your instructor has prepared a series of study guides, one for each class, to assist you in learning
the fundamentals of cellular and molecular neuroscience. Study guides 1-3 will become available
two weeks before the start of class. Each subsequent guide will come out a week in advance of
the corresponding class. Each study guide includes lists of learning objectives, recommended
textbook readings, recommended resources to consult before and after class, and one or more
study questions.
Study questions are for learning – they will not be graded, although for full credit you do need to
submit answers by the due date. Feedback on the study questions (a.k.a., the answer key) will
become available no later than one week after each corresponding class.

Introduction  to  the  study  guides  
Learning  the  fundamentals  of  neuroscience  
Prior to each class you are urged to:
• complete any recommended followup work from the previous class
• read the recommended sections of the textbook
• review the PowerPoint notes pages posted in Resources
• review any additional recommended resources
Following each class you are urged to:
• obtain help with any concepts with which you are having difficulty
• try to answer the study questions on your own, then work with your group if necessary
To develop complete confidence in your understanding of the material and in your ability to
apply the related skills, you are strongly encouraged to work in groups and come in for office
hours if and when you need help with any of the material.


tutorials folder) • capacitance. especially if you have a weak background in the physical sciences. What is meant by the neuron doctrine? Be prepared to cite evidence that clearly established the role of neurons as the basic functional units of the nervous system. such as the discussion of dendritic spines. What you should be able to do following this class • You should be able to articulate the contradictory views of the role of the brain in behavior throughout the 19th century and half of the 20th and cite evidence that was used to support the opposing views. in your own words. and the neuron doctrine. but if you have time.pdf (Resources section. • Purves Ch 1 "Studying the nervous system" introduces model organisms." • basic_electricity. neural circuits. including the properties of charged particles and electric current. including online access to journal articles. then the following readings will get you off to a very good start. Some of the information. • Be able to access primary literature online. tutorials folder) • Electricity 1 (Tests & Quizzes) Studyguide  1  –  22  Aug  16   Mon  Aug  22:  A  biological  basis  for  behavior   Class notes: 01_Intro_F16. Be able to describe. may prove valuable later. reticular theory.pdf" in the Tutorials folder in the Resources section.pdf Recommended textbook reading: None assigned. M. and Ohm's Law. 2006. • Nicholls Ch 1 "Principles of signaling and organization" introduces important topics that will be introduced in the first few weeks of the course. This article nicely follows (or precedes) the discussion in class of Cajal.pdf (Resources section. Golgi. • Kandel Chs 1 & 2 are a useful introduction to the entire course.Before  the  first  class:  recommended  resources  and  assessment   A solid understanding of how neurons and nervous systems function requires reasonable familiarity with basic electricity.       2   . You should have direct access but if not then you may need to use the Library's OneSearch tool. tutorials folder) • Ohms_Law. neurons and glial cells. the models for the roles of the brain and neurons that were finally accepted. Golgi and Cajal: The neuron doctrine and the 100th anniversary of the 1906 Nobel prize. touching on several of the topics to be covered later in more detail. Accessing journal articles: As a member of Rice University you have full library privileges. Follow-up article (online): Glickstein. Current Biology 16(5): R147-R151. neural systems. If you do not know how to access online materials from Fondren Library then you will want to open and follow the tutorial "Retrieving_ journal_articles. and why they were accepted. and much of the terminology to be used in the course.pdf (Resources section. Even students with a strong background in the sciences may benefit from completing the assessment "Electricity 1. You may want to review one or more of the tutorials listed below.

Nevertheless. how neurons communicate via synapses." In particular. To predict the influence of any intervention on Em we must be able to predict the direction in which an ion moves and the magnitude of the electric current that its movement produces. taking a historical. The first model that attempted to explain why cells have membrane potentials suggested. Animal electricity and the birth of electrophysiology: The legacy of Luigi Galvani. that Em is the equilibrium potential for potassium. Brain Res Bull 46(5): 381-407. We will cover this material in much more detail. producing a temporary change in Em that serves as a signaling mechanism in the form of a graded potential or an action potential. Why was it considered unlikely that a nerve axon passively conducts electricity all the way from the input side to the output side? How did Hermann's model get around this problem? Follow-up article (online): Piccolino. An equilibrium potential is the electrical potential difference that results from an asymmetric distribution of a single type of ion across a semipermeable membrane. 1998. In excitable cells including neurons. To do so we must learn to work with equilibrium potentials.Equilibrium  potentials   All living cells maintain an electrical potential difference (Em) across their plasma membranes. and not an equilibrium potential. this article is a nice review of the progress of science from the discovery that animal tissue has electrical properties up to the Hodgkin-Huxley experiments. and how various stimuli activate (or in some cases deactivate) sensory receptor cells. "Electrical signals of nerve cells" p. Studyguide  2  –  24  Aug  16   Weds  Aug  24:  Animal  electricity   Class notes: 02_AnimElec_F16. pages 10-15 provide an overview of material to be covered today. and receptor cells. Marco. external or internal stimuli cause ion channels to open and/or close. 25-36 concisely introduces the electrical properties of neurons. Ch 6 "Ionic Basis of the Resting Potential" presents theory behind the resting membrane potential along with some experimental evidence. experimental approach. the concept of an equilibrium potential is absolutely critical toward understanding how nerve and muscle cells generate and conduct action potentials.     3   . muscle cells. • Be able to articulate the rationale behind the model of the resting potential as an equilibrium potential and Bernstein's explanation for action potentials. It turns out that for most cell types Em is a diffusion potential resulting from asymmetric distributions of two or more ions. For students interested in the history of neuroscience.pdf Recommended textbook reading: • Purves Ch 2. • Nicholls Ch 1 "Principles of signaling and organization. incorrectly. What you should be able to do following this class • Be prepared to cite the evidence that neural activity is electrical in nature and why for so long there was much reluctance to accept a role for electricity in nerve signaling.

4   . This article discusses the scientific impact of JZ Young's 1938 publication on the function of squid giant nerve fibers. • [access through Fondren] Keynes. is Chapter IV from the 1917 book by Keith Lucas (published posthumously). The Adrian article. • [Tests & Quizzes] "Equilibrium potentials" (two parts) uses a simple model to present the basic equilibrium potential concept. that is. One difference between the example in Equilibrium potentials pt 1 and a real cell is that the resting potential difference Em across a cell membrane is usually NOT an equilibrium potential. action. Recommended textbook reading: • Purves Ch 2 "Electrical signals of nerve cells. and explain the findings and their significance. generator. Ion  movement  pt  1   Movement  of  ions  that  are  not  in  equilibrium   Our two compartment model represents an artificial situation. The due dates are spread out to facilitate the learning value. Richard.pdf. This tutorial is also available in Resources as a pdf (ion_movement. of course." When ion channels open and ions cross a cell membrane. It describes the rationale behind the vapor cooling experiment using the straightforward language of the day." • Nicholls Ch 8 "Electrical signaling in neurons.Related tutorials: It will probably be of benefit to spread the tutorials out a bit. make sure that you have all of the principles well in hand. • [Tests & Quizzes] "Ion movement pt 1" (two parts). and wait a bit before moving on to the next one. and receptor potentials in neurons. what happens to the ion concentrations on both sides? Knowing how to answer this question is critical to developing an intuitive understanding of resting. Be able to explain what predictions could or could not be tested in the early 1900s and why. we need to know how ions move when Em ≠ Eion. when the membrane potential is not the same as the equilibrium potential of the ion. You might want to work with it as a group. To fully understand how ions support signaling within neurons. cite experiments that tested the predictions.pdf). Studyguide  3  –  26  Aug  16   Fri  Aug  26:  Testing  the  Bernstein  hypothesis   Class notes: 03_F16_Testing." What you should be able to do following this class •   You should be able to make predictions that follow from the Bernstein model for electrical activity in cells. J Exp Physiol 208: 179-180. What happens to permeant ions when a system is not in equilibrium? Part 2 provides a study question.pdf Recommended articles: • [in Resources] Adrian1917_chIV. • [Tests & Quizzes] "Ion movement pt 2. Complete the first one. 2005. now in the public domain.

Why did the appearance of these features lead to a revision of the Bernstein model for resting and action potentials? Be prepared to cite experiments that supported the sodium theory and the diffusion potential model and explain the rationale.pdf Recommended article: [access through Fondren] Hodgkin. It is not designed to test you for prior knowledge and no grade will be recorded. and their respective influences on nerve activity. Box 2C "Action potential form and nomenclature" p. Be prepared to explain the importance of the re-discovery of the squid giant axon to neuroscience. Completing this tutorial will be a formative (learning) experience. Related tutorial: [Tests & Quizzes] "Ion currents" works through principles governing movements of ions through channels. Be able to explain how a diffusion potential differs from an equilibrium potential. 39 • Nicholls Ch 6 "Ionic basis of the resting potential" • Kandel Ch 6. "Action potentials recorded from inside a nerve fibre. Ion  movement  pt  2   When ions move across a cell membrane. the currents that they carry. If you carefully peruse this brief communication by Hodgkin and Huxley reporting the first recorded intracellular action potential you should find the answer to one of the study questions. what is the impact on the intracellular concentration? This tutorial can be a real eye-opener! It is designed to dispel a common misconception about membrane potentials that is shared by nearly all beginning (and many advanced) students of neural science. why can a cathodal but not anodal stimulus generate an action potential? • Be prepared to employ one or more analogies to explain the respective roles of passive and active forces in regenerating an action potential. "Membrane potential and the passive electrical properties of the neuron" sums up modern theory regarding membrane and action potentials and provides a good background for the coming class on conduction of the nerve impulse. 36-38. You should be able to look at a recording and know whether it is extracellular or intracellular based upon information provided. For example. and the effects of ionic currents on Em. Be 5   ." Nature 144: 710-711. What  you  should  be  able  to  do  following  this  class   • •   Be able to distinguish the features and significance of extracellular versus intracellular recordings including polarity and relative magnitudes. 1939.• Be able to distinguish a cathodal from an anodal stimulus and threshold from subthreshold stimulus. Studyguide  4  –  29  Aug  16   Mon  Aug  29:  Discovering  the  diffusion  potential   Class notes: 04_F16_Discover. Recommended textbook reading: • Purves Ch 2 "Electrical signals of nerve cells" p. Be able to cite experiments involving extracellular recordings that led up to the Hodgkin and Huxley voltage clamp experiments and what their results revealed. Be able to explain the significance of the features of the first intracellular recording of a nerve action potential. AL and AF Huxley.

Learning these strategies will help you with quantitative problems that may appear on a homework set or exam. Copyright laws prohibit posting of the article on Owl-Space. Given sufficient information. V = iR is both one of the most important principles in electricity and (thankfully) one of the simplest. the direction of electric current carried by the ions. Studyguide  5  –  31  Aug  16   Weds  Aug  31:  Ionic  basis  of  the  action  potential   Class notes: 05_F16_IonicBasis. Several study questions will address these objectives. Working with the Nernst & GHK equations: [Tests & Quizzes} "Nernst and GHK" includes five additional study questions in which you work with the two equations to solve quantitative problems. Ohm’s Law applies not only to electrical circuits but also to the movement of ions through membrane channels. Ohm’s Law can be written as E = iR. Pirta Hotulainen et al. and R is the resistance to current flow. whether or not an ion is in equilibrium. Ohm’s Law. and/or permeability coefficient for an ion.014. Assigned journal article In class today you will receive copies of a public release from EurekAlert! Science News and selected pages from the corresponding journal article. Related tutorial: [Tests & Quizzes] "Ion conductance" (two parts) introduces another way of measuring ion and current flow through membrane channels.04.2015. Ion  currents   Directions  and  magnitudes  of  ion  and  current  flow  and  their  effects  on   Em   It is important to be able to predict the direction in which specific ions will move.pdf     6   . be able to use the Nernst and/or Goldman equations to determine intracellular concentration of an ion. knowing the relevant ion concentrations. You are encouraged to go through the tutorial before the next class on the ionic basis of the action potential. posted in Resources in the folder (you guessed it!) Reading guides. can be accessed by anyone with a campus internet connection or off-campus VPN connection. For complete instructions please see the reading guide for this article.devcel. MIM-Induced Membrane Bending Promotes Dendritic Spine Initiation.prepared to determine an equilibrium potential or diffusion potential. Is the ion movement polarizing (making Em more negative) or depolarizing (making Em more positive)? We may also need to estimate magnitude of current flow using Ohm’s Law. Part 2 presents a multiple part study question. Developmental Cell. where E (volts) is the electromotive force. and the impact on Em when an abrupt change in membrane permeability to one or more ions perturbs the steady state. June 2015 DOI: 10.1016/j. i is current.. The complete article.Eion) in place of V or E. cited below. When we are working with ion flow across membranes we use the expression (Em .

Eion. Ion conductance refers to the ease with which an ion passes through a single channel or through many channels in a cell membrane. • • Be prepared to explain the rationale behind the models of the resting and action potentials. 158 Recommended for review: Two potential conceptual stumbling blocks for this class are how an ion moves with respect to its equilibrium potential and the meaning of ion conductance. for intercellular signaling. folder “electricity”) on OwlSpace should help with the concepts introduced in this tutorial. for sensory reception. one siemens = one ampere-volt-1 (i. Box 3A "The voltage clamp method" page 42. Movements of ions across cell membranes are responsible for the electrical currents that produce the resting. or intracellular concentration of an ion. Here are some reasons for learning to work with ion conductance. • • Be able to explain the principle behind use of a Ag/AgCl electrode for measuring Em and injecting or withdrawing current.. • Ion currents • Ion conductance What you should be able to do following this class • • Be able to explain the principles of voltage clamping and its use in studying very rapid membrane-mediated events. and to predict whether or not the circuit will have to inject or withdraw current to maintain a constant membrane potential. all-or-none action potential. and action potentials that are so important for cell maintenance. • • You should be able to explain how the timing of Na and K voltage-gated channels results in a fast. and for motor control. 41-49 • Nicholls Ch 7 "Ionic basis of an action potential" • Kandel Ch 7 "Propagated signaling: the action potential" up to p. 36. 1 ampere/1volt). The resources on basic electricity and Ohm’s Law (Resources. To study these currents we need to introduce a new electrical term. Box 3B "Threshold" p. present and past. predictable. graded.Recommended textbook reading: • Purves Box 2B "The remarkable giant nerve cells of squid" p. • Changes to gNa and gK are responsible for the action potentials in excitable cells   7   . If you aren't sure of your grasp of these concepts then please go back through the related tutorials. Rearranging.e. CORRECT FEEDBACK: From Ohm's Law: 1 volt = 1 ampere ÷ 1 siemens. Ch 3 "Voltage-dependent membrane permeability" p. Study problems: [Tests & Quizzes] "Nernst and GHK" has you work with these two important equations to calculate unknown variables such as Em. to identify the ion(s) responsible. Ion  conductance   NOTE FOR FALL 2016: There is an error in the feedback to question 2 regarding the physical units that make up 1 siemens. namely ion conductance (gion). 49. • • Be able to explain "capacitive current" • • Be prepared to predict current direction across a membrane at varying clamp voltages and with/without blocking agents.

How fine tuned are these neurons? If a neuron receives a thousand inputs how much difference can one single synapse make?   8   . hundreds. sufficient voltage-gated sodium channels open to support an increased sodium current. To understand the significance of the electrogenic effect it is critical that students completely understand the rationale behind the following two statements. Huxley. What is going on with sodium and potassium currents on approach to threshold? Does it get progressively easier to trigger an action potential. or even thousands of excitatory and inhibitory inputs at once. voltage clamping and patch clamping. At threshold. The electrogenic effect is not responsible for the membrane potential.• • • • Hodgkin. therefore if there were no active transport of these ions the Na+ and K+ gradients would decay. This positive feedback cycle is also called the Hodgkin cycle. Threshold  currents   Potassium  and  sodium  currents  on  approach  to  threshold   When an excitable cell is depolarized quickly enough with a strong enough voltage. With each cycle. it does make Em somewhat more negative than the diffusion potential. are to measure ion conductance of individual channels or areas of membranes Investigators use ion conductance per unit area of membrane as a measure of ion channel density Conductance of mutant ion channels was used to learn how many subunits make up an ion channel The difference between sodium conductance and potassium conductance explains the reversal potentials of cation channels Sodium  pump   Electrogenic  contribution  of  the  Na/K  pump   When we have a diffusion potential. The gradients do not decay because an ATP-dependent sodium pump maintains them by pumping out Na+ in exchange for K+. 1. the pump makes a small direct contribution to the Em. after the physiologist who first proposed the mechanism. sodium ions constantly diffuse in. We refer to this contribution as the electrogenic effect. opening even more sodium channels. A cell at rest is in a steady state in which the pumping of excess sodium ions out of the cell is offset by sodium ions leaking into a cell at a slightly higher rate than the rate at which potassium ions leak out. further increasing sodium current. By pumping out an excess positive ion for each ATP hydrolyzed. and Goldman used ion conductances and Ohm’s Law to derive their equation for the diffusion potential The goals of two of the most important techniques in neuroscience. 2. etc. Em reaches what we call a threshold value. which depolarizes the membrane even more. potassium ions constantly diffuse out. Unfortunately (from the viewpoint of students who are trying to understand these relationships) active transport of Na+ and K+ is NOT electrically neutral. and the sodium and potassium currents are equal and opposite. three Na+ are pumped out for every two K+ pumped in. Passive Na+/K+ exchange is electrically neutral. or does it become more difficult? These questions are important when we consider that neurons may receive dozens.

135 "The functional properties.pdf     9   . You must be able to relate the phases to ion channel activation. and the effects on ion conductance. Box 3C " Multiple sclerosis " p. generation of the action potential.pdf" (Resources: tutorials). 54 • Nicholls Ch 8 "Electrical signaling in neurons" • Kandel Ch 6 "Membrane potential and the passive electrical properties of the neuron" starting on p. 115 of Nicholls' 4th edition of "From neuron to brain.pdf Recommended for review: • You may want to review "capacitance..Studyguide  6  –  2&7  Sep  16   Fri  Sep  2  &  Mon  Sep  7:  Conduction  of  the  nerve  impulse   Class notes: 06_F16_Conduction. What you should be able to do following this class • Be prepared to relate the events of the Hodgkin cycle to the phases of action potential conduction . The role of passively conducted current in action potential regeneration should be clear now.. 30-31. • • • • How do the properties of graded and action potentials differ. refractory period. Tutorials: • "Threshold_currents" (Tests & Quizzes) helps with understanding how neurons generate and propagate action potentials "Sodium pump" (Tests & Quizzes) provides valuable background information for the workshop next Monday Sep 12 Studyguide  7  –  9  Sep  16   Fri  Sep  9:  Ion  channel  function   Class notes: 07_F16_ChanFunc.activation. is adapted from an explanation on p. you will not be asked to reproduce the equations that describe Vx or Vt. which presents the concept of electrical capacitance in circuits and membranes. however you may be asked to use them. timing of opening. Recommended textbook reading: • Purves Box 2A " Passive membrane properties" p." deals with the same subject matter that we will discuss in class.pdf" (Resources: tutorials). • "Heat_analogy. and inactivation. closing. and why? Why does passively conducted current decay with distance down an axon? Why is there a time delay before a membrane downstream from a stimulus or action potential achieves the full change in membrane potential? Be prepared to predict qualitative differences in conduction velocity based upon axon diameter and whether or not an axon has a myelin sheath." This document compares conducted current to conducted heat.

you should be able to: • • • • Explain the rationale and interpret results for the three experiments discussed in class Explain why cells have resting membrane potentials Distinguish the two effects of sodium pump activity. namely (1) maintenance of the sodium and potassium gradients and (2) the electrogenic effect. Studyguide  8  –  12  Sep  16   Mon  Sep  12:  Discovering  the  sodium  pump   ***BRING A CALCULATOR (OR CELL PHONE WITH CALCULATOR APP) TO CLASS TODAY*** In today's class we will go through three of the classic experiments leading to the discovery that an ATP-dependent Na/K exchanger maintains the sodium and potassium gradients. Of course you should know what factors influence channel conductance and you should be able to differentiate between microscopic and macroscopic currents. Class notes: 08_F16_Na_pump.pdf Tutorial: Don't forget to go through the "Sodium_pump" tutorial in Tests & Quizzes before class. Reviewing the class notes and the recommended tutorial on the sodium pump experiments should be adequate preparation for class.Recommended textbook reading: • Purves Ch 4 "Ion channels and transporters" p. 57-69 • Nicholls Ch 4 "Ion channels and signaling" (all) • Kandel Ch 5 "Ion channels" p. 100-110 What you should be able to do following this class You will be presented with experimental situations in which you are asked to predict results such as the magnitude and/or direction of ion movement and/or current. In particular. sodium. or chloride ions? You should be able to interpret current-voltage plots and to prepare current-voltage plots based upon information that you are given.pdf     10   . What you should be able to do following this class By the end of the class you should have a solid understanding of the role of sodium-potassium ATPase (the sodium pump) in cells. what mechanisms can make a channel specific for potassium. In what ways do channels select for specific ions? For example. You might be asked to design an experiment or explain why an experiment is or isn't practical. and their significance in terms of resting membrane potentials Explain why the inward sodium current exceeds the outward potassium current in a cell at rest Studyguide  9  –  14-­‐16  Sep  16   Wed  &  Fri  Sep  14  &  16:  Studying  channel  structure   Class notes: 09_F16_ChanStruc.

116-123 What you should be able to do following this class • Be prepared to predict the orientation of a membrane protein and number of transmembrane segments from a hydropathicity map and/or use a diagram of a channel subunit to predict the pattern of signal sequences in an mRNA transcript coding for a channel subunit.pdf   11   . including channels that serve very different functions. Studyguide  10  –  19  Sep  16   Class notes: 10_F16_ChanDiver. such as conducting anions instead of Dynein • https://www. • www. but it is very clear): A Google search will turn up some longer animations that you may find useful.reading is rather tedious) • Nicholls Ch 5 "Structure of ion channels" (all) • Kandel Ch 6 "Ion channels" • www. 116-123 What you should be able to do following this class Be prepared to explain what sorts of modifications of the same basic protein "architecture" have produced an incredible diversity of channel Recommended textbook reading: • Purves Ch 4 "Ion channels and transporters" (all) • Nicholls Ch 5 "Structure of ion channels" (all) • Kandel Ch 6 "Ion channels" p.Recommended video clip: • Membrane protein insertion video (might be a bit elementary.pdf Recommended videos: Kinesin I picked these two because they are relatively • Be prepared to apply one or more of the experimental strategies that we examined in class for learning about channel structure and subunit structure Be prepared to suggest ways in which expression of channel proteins in Xenopus oocytes might be used to reveal channel structure. Studyguide  11  –  21  Sep  16   Weds  Sep  21:  Introduction  to  synaptic  transmission   Class notes: Recommended textbook reading: • Purves Ch 4 "Ion channels and transporters" • Purves Ch 6 "Neurotransmitters and their receptors" (use for reference .

membrane potential.Recommended textbook reading: • Purves Ch 5 "Synaptic transmission" p. • Be prepared to cite observations that can be made in order to determine whether a receptor is ionotropic. 207-210 • Kandel Ch 10 "Overview of synaptic transmission" (all) What you should be able to do following this class • Be prepared to identify a general type of synapse based upon properties that are described for it." The second exam period begins with "Presynaptic mechanisms – role of calcium. First  exam   The exam. will include questions on material from the beginning of the course through "Introduction to synaptic transmission. and some of the challenges facing such transport. metabotropic." Nernst  and  GHK   Here are a few more study questions that focus on quantitative work. 77-81 • Nicholls Ch 11 "Mechanisms of direct synaptic transmission" p. or electrical • Be able to describe the mechanisms by which materials are transported from soma to axon terminal.   12   . or intracellular concentration of an ion. 185-187. You will need to be comfortable using the Nernst and/or Goldman-Hodgkin-Katz equations to calculate an equilibrium potential. scheduled for Sep 30.