Neat!

Course material - NRSC500 (2017-2018*)

*Remember this schedule is subject to change.

All Classes will be in Conference Room 3402A/B in the Djavad Mowafaghian Centre for Brain Health, 8:30am to 10:30am Monday, Wednesday, & Friday, unless otherwise noted.

Handouts will be distributed through the shared folder. If you do not have access, please email the Neuroscience Program Secretary. New handouts will be uploaded when they are available.

    Important dates:

  • TBC. Doctoral Scholarship Applications (Affiliated Fellowships, Tri-Agency) due @ 2pm
  • Oct 20. CIHR Project Approval Due
  • Oct 23. Midterm Exam - Modules 1 & 2
  • Nov 3. CIHR Project Summary Due
  • Nov 11-16. Society for Neuroscience Annual Meeting, no classes
  • TBC. Masters Scholarships Applications (Affiliated Fellowships, CGS masters awards) due
  • Dec 11. CIHR Grant Assignment Due at 4:00 pm
  • Dec 15. Final Exam - Modules 3 & 4


Introduction

Sept. 6

Introduction to the course: CIHR grant assignment, deadlines, student intro, student services. Cell Biology of the Neuron
Dr. Tim Murphy & Dr. Liisa Galea

Reading:

Kandel: Chapter 4


  • Basic Cell Biology of the Neuron

Mod 1: Biophysics of ion channels (Lynn Raymond & Brian MacVicar)

Sept. 8

Software Bootcamp I
Dr. Jeff Ledue

Reading:



  • Matlab, general introduction working with data arrays and random number generation and statistics examples distribution analysis, plotting

Sept. 11

Software Bootcamp II
Dr. Jeff Ledue

Reading:



  • Python, general introduction working with data arrays and random number generation and statistics examples, distribution analysis, plotting, uses material from the Allen Institute Python boot camp

Sept. 13

Resting Membrane Potential
Dr. Lynn Raymond

*Students should bring their laptop computers and be prepared to connect to WIFI. We will be using the following website: www.metaneuron.org to demonstrate some of the concepts taught in the lecture.

Reading:

Kandel: Chapter 6, Chapter 2 for general introduction to neurobiology


  • The ionic composition of the intracellular and extracellular spaces.
  • Electrochemical gradients.
  • Ohm's Law.
  • The Nernst equation.
  • Ionic basis of the resting membrane potential.
    • K+ permeability
    • impermeable intracellular anions
    • Na+/K+ ATPase

Sept. 15

Molecular Biology of Voltage- and Ligand-Gated Ion Channels 
Dr. Lynn Raymond

Voltage and current clamp techniques, pitfalls and neuronal modelling
Dr. Nick Weilinger

Reading:

Kandel: Chapter 5

Ahern et al., 2016. J Gen Physiol. 147 1-24.


  • An overview of the structure and function of voltage- and ligand-gated ion channels.
  • Techniques for electrophysiological recording, when and how to use, pitfalls, etc.

Sept. 18

Action Potential I: Conduction and Cable Properties
Dr. Jeremy Seamans

*Students should bring their laptop computers and be prepared to connect to WIFI. We will be using the following website: www.metaneuron.org to demonstrate some of the concepts taught in the lecture.

Reading:

Kandel: Chapters 6,7


  • Structure and function of Na+ channels.
  • Propagation of the action potential.
    • cable properties of neuronal membranes
    • myelination speeds action potential propagation
  • Recapitulation of resting membrane and action potentials.
  • Emerging role of dendrites

Sept. 20

Action Potential II: Sodium and Potassium Conductances
Dr. Jeremy Seamans

Reading:

Kandel: Chapters 6,7


  • The classic action potential is produced by the interplay of Na+ and K+ channels.
  • Na+ and K+ channels are voltage-dependent ionic channels.
    • selectivity
    • activation
    • inactivation
    • pharmacology
  • The voltage-clamp measures membrane current.
  • The Na+ current is self-sustaining.
  • Absolute and relative refractory periods.
  • The afterhyperpolarization and Ca++-dependent K+currents.

September 19th: Applications for Affiliated Fellowships - Doctoral Level, NSERC Doctoral Award due

Sept. 22

Voltage-Gated Ion Channels: Potassium channels
Dr. Brian MacVicar

Calcium Channels
Dr. Terry Snutch

Reading:

Hille: Chapter 5
Jan and Jan, Annu. Rev. Neurosci. 20:91-123 (1997)

Hille: Chapter 4


  • The role of K+ channels in neuronal function.
  • A brief survey of the growing list of K+ channels.
  • The A-type K+ channel as an example of a voltage-gated K+ channel.
  • The ATP-sensitive K+ channel as an example of a ligand gated K+ channel.
  • A quick overview of voltage gated ion channels.
  • Calcium channels are diverse in structure, pharmacology, and function: HVA channels and LVA channels.
  • Basic structure of HVA channels: subunits and organization.
  • Map of the HVA family ?1 subunit: important molecular features.
  • Calcium channels are topographically organized within the cell.
  • Disorders associated with calcium channels: pharmacology and genetics.
  • Questions, review of abstracts and discussion of labs doing cool calcium channel stuff

Sept. 25

Molecular Approaches in Neurobiology
Dr. Ann Marie Craig

Reading:

Alberts (Molecular Biology of the Cell): Chapter 8 (4th, 5th Ed) "Manipulating Proteins, DNA and RNA"
or
Alberts: Chapter 7 (3rd Ed) "Recombinant DNA Technology"


  • Overview of cellular and molecular methods applied to Neuroscience.
  • With focus on nucleic acids and protein.

Sept. 27

Review Session
Dr. Lynn Raymond & Dr. Brian MacVicar

Homework set is due at this lecture and will serve as starting point


  • A chance to practice principles of neuronal electrical properties by solving problems.
  • Review of all Module 1 lectures. Students should come prepared with specific questions about the material covered during this time period.

Mod 2: Synaptic transmission, ligand-gated ion channels ( T Murphy & AM Craig )

Sept. 29

Discussion on Molecular Methods
Dr. Ann Marie Craig

Intro to Microscopy and Molecular Methods
Dr. Kurt Haas

Reading:

Prepare ahead of time for discussion based on the handout in the dropbox



Oct. 2

Neurochemistry I: amino acid and peptide synthesis and degradation
Dr. Tim Murphy

Reading:

The readings are for Neurochemistry I and II.

Fundamental Neuroscience 1st Ed., Chapter 8, p. 193-234 Chapter 14, p.389-392. Or 2nd Ed. Chapter 7 p. 167-196 and Chapter 13 339-360. In 3rd Edition Chap. 7 starting pg.133 and Chapter 12 starting pg. 271.

Cooper, Bloom & Roth, The Biochemical Basis of Neuropharmacology, Chaps. 7-13, 6th Ed or Chaps 6-11 7th Ed.

Molecular Biology of the Cell 4th ed. Chapter 11 or Molecular Biology of the Cell 3rd ed. Chapter 11 p 507-523.


  • Metabolic processes neurons share with other cells and organs.
  • Enzyme and receptor binding kinetics basics, competitive and non-competitive inhibition.
  • Metabolic contingencies imposed by the existence of a blood-brain barrier (i.e. glucose utilization).
  • Properties and functions of enzymes and pumps.
  • Synthesis and metabolism of amino acid neurotransmitters.
    • glutamate
    • aspartate
    • glycine
  • Neurotransmitter transporters.
  • Neuropeptide synthesis and the pathway to regulated release.

Oct. 4

Neurochemistry II: Amine synthesis and degradation
Dr. Steve Vincent

Reading:

Cooper, Bloom & Roth, The Biochemical Basis of Neuropharmacology – chapters on amines, acetylcholine, GABA, purines, cannabinoids.


  • Regulation of catecholamine, indoleamine, and acetylcholine metabolism.
  • Synthesis, uptake, release, etc.

Oct. 6

Synaptic Transmission I
Dr. Tim Murphy

Reading:

Fundamental Neuroscience 1st Ed. Chapters 7 and 8 (for Neurochem also), 2nd Ed. Chapters 7 and 8., 3rd Ed. Chapters 7 and 8.

Molecular Biol. Of the Cell 4th Ed. Chapter 13. Harold L. Atwood & Shanker Karunanithi Diversification of synaptic strength: presynaptic elements. Nature Reviews Neuroscience 3, 497 -516 (2002). Advanced review comprehensive.

T. Galli, V. Haucke, N. R. Gough, Synaptic vesicle fusion followed by clathrin-mediated endocytosis. Sci. STKE 2003, tr3 (2003) shockwave animation of ves. fusion.

T. Südhof The synaptic vesicle cycle. Annu. Rev. 2004 Vol. 27: 509-547


  • Discovery of chemical transmission.
  • Criteria for transmitter status.
  • Ionic requirements for transmitter release: calcium.
  • Properties of presynaptic calcium channels.
  • Quantal aspects of release.
    • Release and recycling of vesicles
  • Biochemistry of release.
    • Synaptic vesicle protein cycle
    • v- and t-SNAREs, common aspects of all secretion
    • Presynaptic modulation of release.
    • Activity dependent modulation, autoreceptors, neuromodulation, readily releasable pool.
  • Synapses as computational devices.
    • Presynaptic inhibition, facilitation, paired pulse depression, quantal aspects of release etc.

  • Monday October 9th: Thanksgiving break.

Oct. 11

Synaptic Transmission II: Molecular properties of transmitter release
Dr. Tim Murphy

Reading:

See Synaptic Transmission I



Oct. 13

Ligand-Gated Ion Channels I
Dr. Ann-Marie Craig

Reading:

Readings are for Ligand-Gated Ion Channels I & II

Kandel (Principles of Neural Science 5th Ed): pages 184-235 and pages 1490-1498 (Chapters 9 and 10 and a bit more)


  • Structure specialized for function at two classic synapses
    • neuromuscular junction
    • typical CNS synapse
  • AChR as a model ligand-gated ion channel
    • single channel and macroscopic currents
    • desensitization
    • cloning
    • subunit composition and structure
  • Families of ligand-gated ion channels
  • GABAA receptors
    • structure and modulators
    • inhibitory function in adult
    • developmental switch
    • diversity of subunits
  • GABAergic synapses
    • scaffolding proteins, signaling enzymes, cell adhesion proteins
    • plasticity


Oct. 16

Ligand Gated Ion Channels II
Dr. Ann-Marie Craig

Reading:

(Readings listed under  "Ligand-Gated Ion Channels I" lecture.)


  • Glutamate receptors
    • initial cloning
    • AMPA, KA, NMDA classes
    • structure
    • RNA editing
  • Properties of NMDA receptors
    • glycine co-agonist
    • Ca++-permeability
    • voltage-dependent Mg++ block
    • deactivation
  • Glutamatergic postsynaptic density
    • approaches to identify components
    • PDZ domain scaffolding proteins
  • Synaptic plasticity: hippocampal LTP
    • Hebbian properties
    • NMDAR as molecular coincidence detector
    • silent synapses and AMPAR insertion
  • Synaptic plasticity: other forms
    • LTD
    • homeostatic plasticity


Oct. 18

Student Presentations
Dr. Anne Marie Craig & Dr. Tim Murphy

2-Page Critique Due

 

Presenters bring your Powerpoint presentation to class on USB



Oct. 20

No Class
CIHR Project Approval Due

Oct. 23

Mid-term exam, modules 1-2

9am-12pm

Location: TBD

Mod 3: Second messengers & gene expression ( Weihong Song & Steve Vincent )

Oct. 25

Second messengers: cyclic nucleotides (cAMP,cGMP and nitric oxide)
Dr. Steve Vincent

Reading:

Pierce, K.L., Premont, R.T. and Lefkowitz, R.J. (2002) Seven-Transmembrane Receptors, Nature Reviews in Molecular Cell Biology 3:639-650.


  • cAMP and the concept of intracellular second messengers
  • discovery of G proteins - activation of adenylyl cyclase
  • the family of G protein-coupled receptors
  • G proteins as molecular switches and timers
  • roles for bg subunits
  • actions of cAMP - PKA

Oct. 27

Genetic resources and approaches
Dr. Tara Klassen and Dr. Paul Pavlidis

CIHR Summary Due

Reading:

Metzker (2010). Sequencing technologies - the next generation. Nature Reviews Genetics, 11, 31-46.

Lander (2011). Initial impact of the sequencing of the human genome. Nature, 470, 187-197.

Web Resources:

NCBI: The Mother of all Web Resources

Gene Discovery Page - a guide on how to figure out what genes may do

DNA Microarrays: Whys and wherefores of Gene chips

Jackson Labs - Mouse informatics/gene expression

OMIM- Human Genetic Disorders:
Every mapped human disease gene & what it does

The Human Genome Project:
What it is, where it came from, what it tells us

https://www.alleninstitute.org/our-research/open-science-resources/

http://neuinfo.org/

https://genome.ucsc.edu/cgi-bin/hgGateway


  • Identifying genes responsible for disease/ a specific function
  • Protein modification and the search for interacting proteins
  • model organisms and mice - what we can learn from them
  • The Human Genome Project and what we can learn from it
  • Gene Expression technologies, from SAGE to DNA chips and beyond.

Oct. 30

Optogenetics and Chemogenetics
Dr. Tim Murphy

Nov. 1

Receptor regulation
Dr. Lynn Raymond & Dr. Steve Vincent

Reading:

Mansi Vithlani, Miho Terunuma, and Stephen J. Moss. THE DYNAMIC MODULATION OF GABAA RECEPTOR TRAFFICKING AND ITS ROLE IN REGULATING THE PLASTICITY OF INHIBITORY SYNAPSES. Physiol Rev 91: 1009 –1022, 2011.

Wei Lu and Katherine W Roche. Posttranslational regulation of AMPA receptor trafficking and function. Current Opinion in Neurobiology 2012, 22:470–479

C. Geoffrey Lau and R. Suzanne Zukin. NMDA receptor trafficking in synaptic plasticity and neuropsychiatric disorders. NATURE REVIEWS NEUROSCIENCE.VOLUME 8,JUNE 2007, 413


  • Ligand-gated ion channel regulation
    • Homologous and heterologous regulation
    • Molecular mechanisms, including changes in desensitization, peak amplitude and numbers of available receptors
    • G-protein coupled receptor regulation
    • Desensitization
      • G-protein coupled receptor kinases (GRKs)
      • Arrestins
      • PKA, PKC
      • Palmitoylation
      • Receptor endocytosis
    • Downregulation
    • Receptor degradation
    • Decreased synthesis

Nov. 3

Control of Neural Gene Expression
Dr. Weihong Song

Reading:

Bito H, Deisseroth K, and Tsien RW (1997) Ca2+-dependent regulation in neuronal gene expression. Curr Opin Neurobiol 7:419-429.

Sun et al (2006). Hypoxia facilitates Alzheimer's disease pathogenesis by upregulating BACE1 gene expression. PNAS 103:18727-18732

Alberts et al., Mol. Biol. of the Cell Chapter 9, 409-469.


  • Basic transcription machinery
  • Mechanisms of regulated gene expression
  • Families of transcription factors
  • cAMP response element
  • Immediate early genes
  • Steroid receptor family
  • Homeoboxes

Nov. 6

Prions, protein folding and misfolding
Dr. Neil Cashman

Reading:




Nov. 8

Second Messengers: Calcium and IP3
Dr. Brian MacVicar

Reading:

Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nature Reviews in Molecular Cell Biology 1: 11-21, 2000.

Gu and Spitzer, Distinct aspects of neuronal differentiation encoded by frequency of spontaneous Ca2+ transients. Nature 375: 784-787, 1995.


  • IP3 and DAG production and actions and metabolism
  • IP3 and ryanodine receptors
  • cADP-ribose, production and action
  • Targets for the actions of calcium (calmodulin, calcineurin etc.)
  • Calcium waves, calcium oscillations
  • The AM and FM of calcium signalling (with neuro examples)

Nov. 9

Non-selective cation channels
Dr. Brian MacVicar

Reading:

Chapter 10, 23 (pg 555-­-556) Intracellular signaling

Ramsey et al (2006) An introduction to TRP channels. Ann Rev Physiol 68:619-­-647

Minke & Cook (2002). Physiol Rev. 82, 429­-472.

Goodenough & Paul (2003) Beyond the gap: Functions of unpaired gap junctions. Nat Rev Molecular Cell Biology 4, 285-295.

MacVicar, BA and Thompson, R (2010) Non-­junction functions of pannexin-1 channels. TINS 33:93-102.


  • TRP(transient receptor potential) channels
  • connexin and pannexin hemichannels
  • CNG (cyclic nucleotide gated) channels

November 11-16: SFN Conference No Class


Nov. 17

Lipids and Lipoproteins in the CNS
Dr. Cheryl Wellington

Reading:



  • Lipid types and involvement with signalling in the CNS.

Nov. 20

Epigenetic variation in human health and disease
Dr. Michael Kobor

Reading:



  • Epigenetics at the Interface of Genome and Environment
  • Epigenetic Variation in Adults
  • Biological Embedding of Early Life Experiences
  • Genetic Determinants of Epigenetic Variation
  • Epigenetics in Human Neurological Disease

Nov. 22

Student Presentations
Dr. Steve Vincent & Dr. Weihong Song

2-Page Critique Due

  Mod 4: Development (Tim O’Connor)

Nov. 24

Nervous System Induction
Dr. Tim O’Connor

 Reading:

Movie: Xenopus development

Nov. 27

Proliferation and Differentiation
Dr. Doug Allen

Reading:

Lui J.H., Hansen D.V., Kriegstein A.R. Development and Evolution of the Human Neocortex. Cell 146 (2011), 18-36.

Manent J.B., Beguin S., Ganay T., Represa A. Cell-autonomous and cell-to-cell signalling events in normal and altered neuronal migration. Eur. J. Neurosci. 34 (2011), 1595–1608.

Nov. 29

Process Outgrowth and Neural Pathfinding
Dr. Tim O’Connor

Reading:


Masters Scholarships Applications (Affiliated Fellowships, CGS masters awards) due around here

Dec. 1

Synaptogenesis
Dr. Kurt Haas

Reading:

Washbourne, P., Dityatev, A., Scheiffele, P., Biederer, T., Weiner, J. A., Christopherson, K. S., and El-Husseini, A. (2004) Cell Adhesion Molecules in Synapse Formation. J. Neurosci. 24, 9244-9249

Kim E, Sheng M. PDZ domain proteins of synapses. Nat Rev Neurosci. 2004 Oct;5(10):771-81.

Yukiko Goda and Graeme W. Davis. Mechanisms of Synapse Assembly and Disassembly. Neuron 2003: 40 (2) 243-264

Sanes JR, Lichtman JW. Induction, assembly, maturation and maintenance of a postsynaptic apparatus. Nat Rev Neurosci 2001 Nov;2(11):791-805

Moss SJ, Smart TG. Constructing inhibitory synapses. Nat Rev Neurosci. 2001 Apr;2(4):240-50.

Dec. 4

Activity and Circuit Formation
Dr. Kurt Haas

Reading:


Dec. 6

Cell Death in the Nervous System
Dr. Shernaz Bamji

Reading:


Dec. 8

Student Presentations and Review
Dr. Tim O’Connor & others

2-Page Critique Due

 

Dec. 11

Final Exam, modules 3-4

9am-12pm

Location: TBD

Friday December 15th: CIHR Grant Assignment Due at 4:00 pm

UBC