neurophys4

neurophysiology2.md

@@ -115,11 +115,22 @@ The current flowing back into the axon and thus across its membrane can be measu
 **This electronic feedback circuit** holds the membrane potential at the desired level, even in the face of permeability changes that would normally alter the membrane potential. (such as those generated during the action potential). Most importantly, the device permits the simultaneous measure of the current needed to keep the cell at a given voltage. This current is exactly equal to the amount of current flowing across the neuronal membrane, allowing direct measurement of these membrane currents.
 
 
->An amplifier, electronic amplifier or (informally) amp is an electronic device that can increase the power of a signal. It does this by taking energy from a power supply and controlling the output to match the input signal shape but with a larger amplitude.
+amplifier, electronic amplifier  
+: "amp"  
+: electronic device that can increase the power of a signal 
+: uses energy from a power supply and controls an output signal to match input signal shape, but with greater amplitude
 
->A differential amplifier is a type of electronic amplifier that amplifies the difference between two input voltages but suppresses any voltage common to the two inputs.[1]
+differential amplifier  
+: type of electronic amplifier 
+: amplifies difference between two input voltages and suppresses any voltage common to the two inputs
+: op-amp  
 
->An operational amplifier (often op-amp or opamp) is a DC-coupled high-gain electronic voltage amplifier with a differential input and, usually, a single-ended output.[1] In this configuration, an op-amp produces an output potential (relative to circuit ground) that is typically hundreds of thousands of times larger than the potential difference between its input terminals.[2]
+operational amplifier  
+: <https://en.wikipedia.org/wiki/Operational_amplifier>
+: "op-amp" 
+: DC-coupled electronic amplifier  
+: differential input and often a single output  
+: can produce an output potential many thousands of times larger than the voltage difference between inputs  
 
 
 ---
@@ -144,9 +155,13 @@ So the experiment was to hold the membrane potential at different voltages and m
 
 ## Electric current flow across a squid axon membrane during voltage clamp
 
-<div><figcaption class="big">negligible current (except for a capacitive transient)</figcaption><img src="figs/Neuroscience5e-Fig-03.01-1R_5455913.png" height="300px"><figcaption>Neuroscience 5e/6e fig. 3.1; from Hodgkin et al., *J. Physiol.* 1952</figcaption></div>
+<div><figcaption class="big">negligible current (except for a capacitive transient)</figcaption><img src="figs/Neuroscience5e-Fig-03.01-1R_5455913.png" height="300px"><figcaption>
 
-<div><figcaption class="big">inward and outward currents</figcaption><img src="figs/Neuroscience5e-Fig-03.01-2R_49ec352.png" height="300px"><figcaption>Neuroscience 5e/6e fig. 3.1; from Hodgkin et al., *J. Physiol.* 1952</figcaption></div>
+Neuroscience 5e/6e fig. 3.1; from Hodgkin et al., *J. Physiol.* 1952</figcaption></div>
+
+<div><figcaption class="big">inward and outward currents</figcaption><img src="figs/Neuroscience5e-Fig-03.01-2R_49ec352.png" height="300px"><figcaption>
+
+Neuroscience 5e/6e fig. 3.1; from Hodgkin et al., *J. Physiol.* 1952</figcaption></div>
 
 <div style="font-size:0.7em; margin:25px 0;">Inward current is always downward deflection from zero in these traditional voltage clamp plots. Outward current is an upward deflection. </div>
 
@@ -180,7 +195,9 @@ However when Hodgkin and Huxley depolarized the membrane, a transient inward cur
 ## Inward & outward currents produced at a series of clamped membrane voltages
 
 
-<figure><figcaption class="big">Voltage clamp recordings from squid axon. Capacitive artifact removed for clarity.</figcaption><img src="figs/Neuroscience5e-Fig-03.02-0_5ee332f.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 3.2; from Hodgkin et al., *J. Physiol.* 1952</figcaption></figure>
+<figure><figcaption class="big">Voltage clamp recordings from squid axon. Capacitive artifact removed for clarity.</figcaption><img src="figs/Neuroscience5e-Fig-03.02-0_5ee332f.png" height="400px"><figcaption>
+
+Neuroscience 5e/6e Fig. 3.2; from Hodgkin et al., *J. Physiol.* 1952</figcaption></figure>
 
 Note:
 
@@ -196,7 +213,12 @@ Notice a few phenonmena in this figure.
 
 ## Relationship between current amplitude and membrane potential
 
-<figure><figcaption class="big">External Na⁺ 440 mM, internal Na⁺ 50 mM, therefore Nernst says **E<sub>Na</sub> = 55 mV**</figcaption><img src="figs/voltage_clamp_currents_summary_plot_7450e0a.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 3.3; from Hodgkin et al., *J. Physiol.* 1952</figcaption></figure>
+<figure><figcaption class="big">
+
+External Na⁺ 440 mM, internal Na⁺ 50 mM, therefore Nernst says **E<sub>Na</sub> = 55 mV**</figcaption>
+<img src="figs/voltage_clamp_currents_summary_plot_7450e0a.png" height="400px"><figcaption>
+
+Neuroscience 5e/6e Fig. 3.3; from Hodgkin et al., *J. Physiol.* 1952</figcaption></figure>
 
 
 Note:
@@ -222,7 +244,9 @@ So it seems like this inward current may be carried by Na ions.
 
 ## Dependence of the early inward current on sodium
 
-<div><img src="figs/Neuroscience5e-Fig-03.04_0d877f5.png" height="500px"><figcaption>Neuroscience 5e/6e Fig. 3.4; from Hodgkin and Huxley *J. Physiol.* 1952a</figcaption></div>
+<div><img src="figs/Neuroscience5e-Fig-03.04_0d877f5.png" height="500px"><figcaption>
+
+Neuroscience 5e/6e Fig. 3.4; from Hodgkin and Huxley *J. Physiol.* 1952a</figcaption></div>
 
 <div><iframe src="https://www.youtube.com/embed/Wd_gKJoo25Y" width="420" height="315"></iframe><figcaption>Squid giant axon voltage clamping</figcaption></div>
 
@@ -267,17 +291,20 @@ Note:
 </div>
 
 <div><img src="figs/1f421_8622cf0.png" height="300px"><figcaption>puffer fish</figcaption></div>
-<div><iframe src="https://www.youtube.com/embed/4g8KeqjSyqg" width="420" height="315"></iframe><figcaption>Simpsons poison tasty fish</figcaption></div>
+
+<!-- <div><iframe src="https://www.youtube.com/embed/4g8KeqjSyqg" width="420" height="315"></iframe><figcaption>Simpsons poison tasty fish</figcaption></div> -->
 
 Note:
 
-Its mechanism of action, selective blocking of the sodium channel, was shown definitively in 1964 by Toshio Narahashi and professor John W. Moore at Duke University, using the sucrose gap voltage clamp technique (Narahashi et al, J Gen Physiol 1964)
+Its mechanism of action, selective blocking of the sodium channel, was shown definitively in 1964 by Toshio Narahashi and professor John W. Moore at Duke University, using the voltage clamp technique (Narahashi et al, J Gen Physiol 1964)
 
 ---
 
 ## Pharmacological separation of inward and outward currents into Na⁺ and K⁺ dependent components
 
-<figure><img src="figs/Neuroscience5e-Fig-03.05-0_99fe22f.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 3.5; from Moore et al. *J Gen Physiol* 1967 and Armstrong and Binstock *J Gen Physiol* 1965</figcaption></figure>
+<figure><img src="figs/Neuroscience5e-Fig-03.05-0_99fe22f.png" height="400px"><figcaption>
+
+Neuroscience 5e/6e Fig. 3.5; from Moore et al. *J Gen Physiol* 1967 and Armstrong and Binstock *J Gen Physiol* 1965</figcaption></figure>
 
 
 Note:
@@ -330,7 +357,9 @@ Can use this to calculate the dependence of Na and K conductances vs. time and m
 
 ## Membrane conductance changes are time and voltage dependent
 
-<div><img src="figs/Neuroscience5e-Fig-03.06-0_757dbce.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 3.6; from Hodgkin and Huxley *J Physiol* 1952b</figcaption></div>
+<div><img src="figs/Neuroscience5e-Fig-03.06-0_757dbce.png" height="400px"><figcaption>
+
+Neuroscience 5e/6e Fig. 3.6; from Hodgkin and Huxley *J Physiol* 1952b</figcaption></div>
 
 
 Note:
@@ -341,7 +370,9 @@ Note:
 
 ## Depolarization increases Na⁺ and K⁺ conductances of the squid giant axon
 
-<div><img src="figs/Neuroscience5e-Fig-03.07-0_fdae974.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 3.7; from Hodgkin and Huxley *J Physiol* 1952b</figcaption></div>
+<div><img src="figs/Neuroscience5e-Fig-03.07-0_fdae974.png" height="400px"><figcaption>
+
+Neuroscience 5e/6e Fig. 3.7; from Hodgkin and Huxley *J Physiol* 1952b</figcaption></div>
 
 
 Note:
@@ -386,7 +417,7 @@ Can also see increases in K conductance during the AP, but this K+ conductance (
 
 ---
 
-## Properties of action potentials explained
+## Properties of action potentials 
 
 <div style="font-size:0.8em;">
 <div></div>
@@ -401,11 +432,11 @@ Can also see increases in K conductance during the AP, but this K+ conductance (
 
 Note:
 
-The threshold is a point of criticality in the system like trying to balance on a knifes edge. Just imagine any self-organized phenomena in nature:  a snow field suddenly turning into an avalanche, liquid water turning into gas or solid forms, videos of cat memes suddenly going viral.  The point at which the states of these systems veer on the edge of order or disorder is the point of criticality also known to physicists as a phase transition.
+The threshold is a point of criticality in the system like trying to balance on a knifes edge. Just imagine any self-organized phenomena in nature:  a snow field suddenly turning into an avalanche, liquid water turning into gas or solid forms, videos of cat memes suddenly going viral.  The point at which the states of these systems veer on the edge of more or less order (or less or more disorder) is the point of criticality, often knownas a phase transition.
 
 ---
 
-## Properties of action potentials explained
+## Properties of action potentials 
 
 * Action potential propagation and directionality?
 * Refractory periods?
@@ -413,7 +444,6 @@ The threshold is a point of criticality in the system like trying to balance on
 
 Note:
 
-Next we will look at the following properties of APs such as:  
 
 ---
 
@@ -424,24 +454,27 @@ Next we will look at the following properties of APs such as:
 
 Note:
 
-First let’s talk about AP propagation.
 
-During an action potential, inward current through Na⁺ channels
+During an action potential, inward current is mediated by Na⁺ influx through sodium channels.
 
 ---
 
-## Passive current flow in an axon
+## Decay of subthreshold signals
 
-<figure><figcaption class="big">subthreshold changes decay rapidly</figcaption><img src="figs/Neuroscience5e-Fig-02.03-1R_aac41b9.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 2.3</figcaption></figure>
+A subthreshold depolarization (like a synaptic potential) decays in amplitude with increasing distance and time from its site of origin (e.g. dendrite branch) on a neuron. 
+
+<figure><figcaption class="big">subthreshold changes decay</figcaption><img src="figs/Neuroscience5e-Fig-02.03-1R_aac41b9.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 2.3</figcaption></figure>
 
 
 Note:
 
+Subthreshold signals. Currents underlying subthreshold signals are also called passive current flow in textbook, or electrotonic decay.
+
 bottom graph shows the peak Vm
 
 ---
 
-## Propagation of an action potential
+## Propagation of regenerative suprathreshold signals 
 
 <figure><figcaption class="big">suprathreshold depolarizations propagate down the axon and don't decay</figcaption><img src="figs/Neuroscience5e-Fig-02.03-2R_4bea3b6.png" height="400px"><figcaption>Neuroscience 5e/6e Fig. 2.3</figcaption></figure>
 
@@ -486,7 +519,7 @@ Active and Passive current flow.
 
 </div>
 
-<div><img src="figs/action_potential_ab5134f.png" height="150px"><figcaption></figcaption></div>
+<div><img src="assets/fig_AP.svg" height="150px"><figcaption></figcaption></div>
 
 Note:
 
@@ -518,6 +551,15 @@ Note:
 Note:
 
 
+myelin  
+: appears to have arisen independently across evolution in vertebrates, annelids, and crustacea  
+: for vertebrates, likely first present in ancestor of sharks and bony fish
+: not present in ancient vertebrates like hagfish and lampreys  
+: not present in molluscs or insects thus far  
+
+[^Hartline2007]: Hartline and Colman Curr Biol, 2007. <http://www.sciencedirect.com/science/article/pii/S0960982206025231>
+
+
 ---
 
 ## Nodes of Ranvier
@@ -552,9 +594,11 @@ red indicates imaged expression of voltage gated Na channels. green indicates a
 
 Note:
 
-figure comparing action potential propagation speed in an unmyelinated and myelinated axon.
+Comparing action potential propagation speed in an unmyelinated and myelinated axon. In either case, a sufficient density of voltage-gated sodium channels must be expressed along the axon membrane. <!-- todo: how many? -->
 
-action potential genaration occurs only at specific points, the nodes of Ranvier, along the myelinated axon
+Regeneration of a spike waveform (action potential) occurs all along the axon (perhaps think of an infinite number of spots).  
+
+Regeneration of a spike waveform occurs at specific points along a myelinated axon, the nodes on the axons in between myelin sheaths (the nodes of Ranvier).
 
 --
 
@@ -573,7 +617,9 @@ onset between ages 20-40.
 
 blindness, motor weakness, paralysis.
 
-ultimate cause of MS remains unclear. Immune system contributes to damage and is key component. Immune cells in CSF and injection of myelin in animals can cause EAE. Autoimmune disorder. Or persistent infection with a human retrovirus?
+ultimate cause of MS remains unclear. Immune system contributes to damage and is key component. Immune cells in CSF and injection of myelin in animals can cause EAE. 
+
+<!-- Autoimmune disorder. Or persistent infection with a human retrovirus? -->
 
 
 * women to men ratio 3/2
@@ -619,4 +665,3 @@ Note:
 Note:
 
 
-