Biological Sciences 300, Smith College | Neurophysiology

Schedule, Spring 2020

http://www.science.smith.edu/departments/NeuroSci/courses/bio330/syllabus.html   [also: tinyurl.com/bio300]

UPDATED: February 20, 2020

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The 2017 syllabus remains available online. It contains links to laboratory exercises,
plus video guides to readings in the fifth edition of Purves et al, Neuroscience.

2020 DATES

TOPICS AND ASSIGNMENTS                                       COMPRESS SCHEDULE

Jan 28-30

ELECTRICAL SIGNALS IN NEURONS

Neurons convey information: sensory receptors for touch.

Rapidly-adapting (phasic) vs. slowly-adapting (tonic) responses.
Code: bigger stimulus = more frequent action potentials.

Case discussion: How accurate is sensory reality?

Example: crustacean muscle receptor organ (MRO or "stretch receptor").
Intracellular recording using microelectrodes.
Electrical potential. Ohm's Law.
Resting, generator and action potentials.
Link between amplitude of generator potential and frequency of action potentials.

Reading: Purves et al, Neuroscience, 6th edition, 2018 ("N6e"), chapter 9, pages 193-201 (touch receptors), emphasizing aspects that correspond to the work we did in the first class; and chapter 2, pages 33-39 (neural signals).

The first weekly quiz will be on Tuesday, February 4, at the start of class, on topics from this first reading assignment. Future quizzes will also be on Tuesdays, beginning February 11.

Textbook information, course requirements, and other Administrative Information are posted online.
The textbook has a companion website with animations and other helpful resources.


Visualizing brains and neurons.
This topic will be covered partly through narrated videos on our Moodle site. Please view these videos before our first class next week:

The unfixed brain (6:19)
The CLARITY technique (4:16)
Connectomics. 1. Mouse retina (2:28)
Connectomics. 2. Retinal ganglion cell dendrites (0:41)
Connectomics. 3. Structure of mouse cortex (3:39)
Connectomics. 4. Method of reconstructing the brain (2:46)
Visualizing individual neurons: general stains, injecting fluorescent dye or dense markers, HRP backfill, lipid-soluble dyes, immunocytochemistry, genetically expressed fluorescent proteins, "brainbow," CLARITY technique, connectomics.

Reading: N6e, Appendix A, pages A1-A4 (brain overview); chapter 1, pages 4-16 and 21-28 (brain imaging). Also explore the 3D brain model at www.brainfacts.org/3D-Brain.

   Collaborative Writing Project Chapter 1 ends here. DUE: Feb 6.

Feb 4-6

MEMBRANE POTENTIALS

Ions, pumps, and membrane potentials.

Squid giant axon. Distribution of ions in axon and blood. Na/K pump: active transport of ions.

Case discussion: Why do red blood cells need pumps?

Forces acting on ions. Equilibrium between diffusion and electrical attraction. Equilibrium potential. Nernst equation.

Ions that can cross membrane carry charge until cell's potential matches the ion's equilibrium potential. Concentrations can be regarded as constant. Preview of the action potential.

Reading: N6e, chapter 4, pages 79-82 (pumps); chapter 2, pages 39-47 (distribution of ions).

View: Animations 4.2: The Sodium-Potassium Pump, 2.1: The Resting Membrane Potential, and 2.2: Electrochemical Equilibrium

Membrane channels for Na+ and K+ ions.

Voltage clamping: command and measured potentials; inject current as needed to maintain "clamped" potential.
Axon: early inward current and late outward current follow depolarization.

Separating currents due to Na ions and K ions (low-Na, TTX, TEA). Na-inactivation.

Case discussion: A lethal shipboard snack.

Calculating conductance for each ion. Peak conductance vs. potential. Peak current vs. potential.

Reading: N6e, chapter 3, pages 49-56 (voltage clamping).

View: five videos on the squid giant axon; Animations 3.1: The Voltage Clamp Method

Feb 11-13

Voltage clamping (continued)

Reconstructing the action potential from voltage-clamp data. Threshold and refractory period.
Na/K pump is not a direct part of the action potential mechanism; it just "cleans up" afterward.

Patch clamping to look at individual channels.

Reading: N6e, chapter 4, pages 65-69 (patch clamping).

Animations 2.3: The Action Potential, 4.1: The Patch Clamp Method


  Collaborative Writing Project Chapter 2 ends here. DUE: Feb 18.

 Propagation of the action potential.

Local circuit currents. Length constant. Conduction velocity. Strategies for faster conduction: giant fibers and myelination. Demyelinating diseases.

Case discussion: The case of the missing channels.

Reading: N6e, chapter 3, pages 57-62 (propagation).

View: Animation 3.2: Impulse Conduction in Axons

  Collaborative Writing Project Chapter 3 (covering only one class) ends here. DUE: Feb 20.

Feb 18-20

Generator channels. Other voltage-dependent channels.

"Generator-type" channels: not electrically excitable. Examples: stretch-activated channels. Reversal potential suggests small positive ions go through the channels.

Initiation of action potentials at nearest low-threshold site.

Calcium and potassium channels (IA, IC) that modulate firing rate of neurons.

Optogenetic channels. Optical recording methods.

Reading: N6e, chapter 4, pages 72-79 (other channels).

Molecular structure of voltage-dependent channels.

Physiological and genetic insights to structure of membrane channels. TTX binding at selectivity filter, pronase attack on inactivation gate. Purification of Na channel protein, sequencing of gene. Deductions about structure and function, S4 helix as probable voltage sensor.

Solving the molecular structure of the bacterial KcsA channel. Location of selectivity filter. Structure of the voltage-gated Shaker channel. Evolution of Ca and Na channels: four domains resembling Shaker channel.

Reading: N6e, chapter 4, pages 69-79 (channel structure).

Videos on K channel structure.

  Collaborative Writing Project Chapter 4 ends here. DUE: Feb 27

Feb 25-27

Feb 25: MetaNeuron simulations. Class meets in 408 Sabin-Reed.
Before class, read the instructions Simulations of Membrane Potentials. We will explore sections 1-5, but not 6 (the mini project).

Feb 27: Review Q&A.

Mar 3

EXAM on membrane potentials, in class (topics through Feb 27 classes and readings).
A copy of a recent exam is posted on our Moodle site.

Mar 5

SYNAPSES

Electrical synapses: structure of gap junctions, examples of electrical conduction.
Neuromuscular junction: structure of pre- and post-synaptic components.

Reading: N6e, chapter 5, pages 85-91 (electrical synapses, presynaptic aspects of chemical synapses [part 1]).

View: Animation 5.1: Synaptic Transmission

Mar 10-12

Presynaptic release of vesicles. Endplate potential. "Minepps." Quantal release..
Release requires depolarization, entry of extracellular calcium through excitable Ca-channels.
Timing and synaptic delay.

Postsynaptic receptors for acetylcholine.
Molecular structure: 5 homologous subunits. Patch clamping: selectivity for small positive ions.

ACh degradation: acetylcholine esterase. Synthesis: choline acetyl transferase. Reuptake and repackaging in vesicles via transporters. Pharmacology of the neuromuscular junction.

Reading: N6e, chapter 5, pages 91-102 (presynaptic); 102-107 (postsynaptic); chapter 6, pages 116-119 (nAChR);


  Collaborative Writing Project Chapter 5 ends here. DUE: Mar 26.

Mar 14-22

Spring break

Mar 24-26

Neuron-to-neuron synapses: spinal motoneurons.
Temporal and spatial summation.
Excitatory synapses. EPSPs. Reversal potential impies Na and K ions involved.
Transmitter: glutamate. AMPA and NMDA subtypes of glutamate receptor
Inhibitory synapses, IPSPs. Reversal potential = Cl ions.
Transmitter: glycine and GABA. Receptors structurally similar to AChR.
Interaction of excitation and inhibition = synaptic integration. Weighting of synapses by location.

Transmitters activating second messengers (metabotropic receptors).

Classical ionotropic (fast) vs. metabotropic receptors (slow).
Three groups of metabotropic second messengers.

Example: autonomic nervous system.
Pre- and post-ganglionic neurons. Parasympathetic and sympathetic innervation of heart. Multiple transmitters create PSPs of different durations (sympathetic ganglion)

Mechanisms of action: collision-coupling to channels, second messengers causing phosphorylation of channels, opening or closing channels.

Modulation at synapses: Multiple second-messenger systems, overlapping pathways, pre- and post-synaptic modulation.

Reading: N6e, chapter 5, pages 107-111 (epsps & ipsps); Appendix A, pages A4-A7 (spinal cord); chapter 6, pages 121-131 (glutamate and GABA); chapter 7, pages 145-166 (second messengers); chapter 21, pages 465-487 (autonomic nervous sytem); chapter 6, pages 131-143 (other transmitters).

View: Animations 5.2 - Summation of Postsynaptic Potentials, 5.3: Ionotropic and Metabotropic Receptors


  Collaborative Writing Project Chapter 6 ends here. DUE: Apr 2.

Mar 31
-Apr 2

GENERATING MOVEMENT.

Levels of control: within muscle cells (graded depolarization and calcium levels). Control at the motor unit (firing frequency and recruitment).

Feedback from spindles and Golgi tendon organs.

Central control of posture and locomotion: command interneurons in crayfish, central pattern generators for locomotion in Tritonia, crayfish, roaches and cats. Role of sensory feedback in CPGs.

Case discussion: Swimming blindly (based on your response papers -- see the Special Assignment below).

Reading: N6e, chapter 16, pages 357-379 (motor control); chapter 9, pages 201-202 (spindle and GTO structure).

View: Animation 16.1: The Stretch Reflex

Special Assignment: Read a brief, classic paper on a central pattern generator that will be distributed in class on Tuesday. Come to class Thursday with a one-paragraph response to the question: Does sensory feedback play a role in the swimming behavior of Tritonia?


  Collaborative Writing Project Chapter 7 ends here. DUE: Apr 9.

Apr 7-9

VISION.

Structure of eyes and retinas. This introductory topic will be covered by two online lessons hosted on our Moodle site. Please view these lessons before Tuesday's class. The remaining topics will be covered in class:

The retina. Visual pigments, responses of photoreceptors to light. Synaptic network. Horizontal cells. Center-surround receptive fields of bipolar cells.

Retinal ganglion cells. Transient (Y) and sustained (X) ganglion cells. Spatial distribution of retinal ganglion cells.

  Collaborative Writing Project Chapter 8 ends here. DUE: Apr 16.

Reading: N6e, chapter 11, pages 233-247 (eye, retina, photoreceptors), 251-258 (retinal circuits).

View: Animations 11.1: Anatomy of the Human Eye, 11.2: Phototransduction, 11.3: Information Processing in the Retina

Apr 14-16

Visual pathway: lateral geniculate nucleus and visual cortex. Simple, complex and "hypercomplex" cells in striate cortex.

Primary visual cortex. Binocular (stereo) vision. Computer-based receptive field mapping. Spatial frequency selectivity.

Reading: N6e, chapter 12, pages 261-269 (visual pathway and striate cortex); Appendix A, pages A13-A20 (thalamus and cortex).

View: Animation 12.1: Visual Pathway. View: Video about Hubel and Wiesel's experiments.

Apr 21-23

Cortical anatomy: Retinotopic map, ocular dominance columns, orientation pinwheels, spatial frequency patches, blobs, cortical layers.

  Collaborative Writing Project Chapter 9 ends here. DUE: Apr 28.

Extrastriate cortex: Pathways for motion and form. Dorsal pathway, area MT, direction and disparity selectivity.

Reading: N6e, chapter 12, pages 269-276 (cortical anatomy), pages 276-279 (extrastriate cortex); and:
Hubel, D.H. (1982) Exploration of the primary visual cortex, 1955-1975. Nature 299: 515-524.

Apr 28-30

Inferotemporal cortex: Ventral pathway to inferotemporal lobe. Objects and faces. Visual perception. Top-down and bottom-up components of visual perception.

Case discussion: Signaling by a face-selective neuron.

Reading: N6e, chapter 27, pages 633-635 (faces); and:
Gross, CG (2008) Single neuron studies of interior temporal cortex.
                        Neuropsychologia 46: 841-852 (distributed in class).

Color vision: retina, LGN, V1. Color patches and blobs. V4: color constancy.

Reading: N6e, chapter 11, pages 246-251 (color vision).

TBA

Cumulative review session (optional). Bring questions!

May 5-8

Final exam, self-scheduled.
A copy of a recent exam is posted on our Moodle site.

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