Nervous system terms etc

Neuro Terms and "quiz"

First, here is a list of useful terms for neurobiology.
Second, here is a quiz of sorts, that asks you to look at various drugs/toxins. Note, the wikipedia entry on Acetylcholine has had the section on "Receptors" merged with the section on "Pharmacology." So, when the quiz asks you to look up the section on receptors, look instead at pharmacology section, which includes sections on receptors.

Nervous System

There is also a screencast of a version of this lecture using the book's slide deck found here.

Here is a slide presentation from Campbell on the topic.

First, the overall system:

We break the system down by a couple of overlapping categories. First we have the Central Nervous System (brain and spinal cord) and the Peripheral Nervous System (connections out to the body). A “nerve” will contain a bundle of nerve cells known as “neurons.” So, a nerve is sort of a conduit with many wires.
The neurons in the PNS may carry signals from the body back to the CNS (sensory or afferent neurons), or from the CNS to the PNS (motor or efferent neurons). There are also “interneurons,” which serve as connectors, primarily in the CNS.

What you control and what you don’t

The PNS will have a set of neurons of whose signals you are aware and/or you control. This voluntary muscle control system is called the somatic nervous system (SoNS). In the CNS, there are also parts of the brain that are part of your voluntary system.
There are also parts of the brain and spinal cord that are not under your control and of which you are not conscious. These connect with the autonomic nervous system in the peripheral system. These neurons sense and control systems such as your pupil dilation, heart rate and breathing, digestive system and more than you really know about including control of hormones.
The autonomic system is broken down further into the Sympathetic and Parasympathetic systems. These systems often work toward opposite goals, not so much antagonistically, but in a complementary manner. Their interaction is critical in homeostasis.
They also differ in the subsets of neurotransmitters and receptors they use.


Often thought of as controlling the “Fight or Flight” response. Signals from this system result in things you associate with when you feel threatened. Your pulse increases, as does blood pressure. Flow of blood and nutrients to the extremities increases at the expense of internal organs (including most of the brain). You are unlikely to notice pain as much. Any other urges (hunger, feeling tired, sex drive) all take a back seat to getting out of trouble.
The neurotransmitters most associated with this system are norepinephrine, epinephrine (also known as noradrenalin and adrenaline) and acetylcholine. Epinephrine and norepinephrine are also hormones…more on that later. The acetylcholine receptors in this system tend to be of a class that also binds the nicotinic acid molecule.
All of these signals are associated with the fight or flight response.
These are your “rest and digest” and “feed and breed” responses (if prefer: "Netflix and Chill). If hunger, sex drive, tiredness etc go out the window when you are running for your life, these are the signals that counteract this response.
The neurotransmitters also include acetylcholine (but usually a different receptor) and GABA (gamma amino butyric acid).


Below is the labeled diagram from the board.

It has most of the terms we discussed. The direction of impulse travel is from left to right in the neuron given. While this is a “typical” rendition, Other shapes occur.
This shows some of the detail of the cytoskeleton, which is rather specialized. Most of the other components you recognized from a typical cell (whatever that means). Note the myelin sheath, made from glial cells, which wraps the axon at regular intervals (not all neurons are myelinated). The nodes between the myelin cells are really what’s important in transmitting an action potential down the axon.

The Synapse

There is nothing really new here: The "pre-synaptic" cell is justing doing stimulated secretion, which works via calcium-stimulate fusion of vesicles at the plasma membrane (mediated by "snap 25," which we met early in the year). The post-synaptic cells is just doing chemical reception.
There are some new things that allow for the regulation of these signals…such as ligand "reuptake" receptors. You may have heard of drugs such as SSRIs, Selective Serotonin reuptake inhibitors.
Here is a closer view of the synapse. The two cells are held in close apposition to each other by proteins not shown. The presynaptic cell, the one sending the signal, releases a neurotransmitter (not conceptually different from any signal molecule). It binds to a receptor on the receiving cell (post synaptic cell), and initiates a response. Again, not very different from any signal event. The response is to initiate an action potential, by activating a channel. There are feedback pathways to make sure the signals stay at the right level. Also, there are specific pathways to remove the neurotransmitter from the cleft between the cells. This is done either by a “re-uptake” receptor, which does what the name implies, or by degrading it enzymatically. The voltage-gated calcium channels shown in the presynaptic cells is one way to initiate the release of neurotransmitters.

This is a link to an amazing reconstruction of a synapse.

Action Potential

We’re going to do a simple version of this really. The time scale of the reaction is milliseconds or less.
It starts with an electrochemical gradient, which all cells have. It’s larger in neurons such that the voltage across the membrane is about -70 millivolts. The gradient is established by pumps like the ones we discussed earlier in the year that pump sodium, potassium calcium and chloride ions asymmetrically across the membrane. There is more Na+ outside the cell than inside. More potassium outside. Since it carries a positive charge, the inside of the cell is net negative in charge. When channels are opened, ions will flow down their electrochemical gradient (attempting to equalize both charge and chemical distribution).
The two main players are ligand-gated sodium channels and voltage-gated sodium channels.
The ligand-gated channels open in response to neurotransmitter. The more neurotransmitter released, the more the ligand-gated channels open. That allows Na+ to flow down gradient and pushes the voltage toward neutral. If it is too weak of a signal, the potential never gets above the threshold shown, and the neuron doesn’t “fire.” However, if enough of the ligand-gated channels open, the voltage reaches threshold and that change in voltage opens the voltage-gated channels.

Voltage-gated channels.

These are special protein structures. They have three states:
  1. closed and ready to respond to threshold voltage
  2. open, allowing ions through
  3. “refractory,” which is closed and not able to respond to voltage
You need all of these states in sequence to get the action potential.
I’m going to link to a good website that shows you the sequence of events.
Have to get to some other things.


This is from chapter 43. You can do the reading there if you find that helpful. Here is a primer on the cells of the immune system that I recommend to get a good overview. Work though the cells of the immune system. When we get together next, we will spend some time playing a couple of games. You don't have to work on that now.

We will start with this
game and also play this one here. You don't need to do this ahead of time, but i would go through the primer on cells.

Here is a nice overview slide of the adaptive response:
Adaptive Overview

Components of the immune system:

Barriers such as skin and mucus, tears etc. form initial barrier

Innate Immunity:

Cell and biochemical defenses against pathogens. These have four main roles:
  1. First responders attack intruders (some specific for particular types of pathogens using recognition receptors).
  2. Cells release pro-inflammatory signal molecules that attract other immune cells to the area (both more innate immunity cells and adaptive cells)
  3. Present antigens for adaptive immunity to surveil
  4. Following adaptation of B-cells and antibody production, some components of innate immunity are targeted more specifically to pathogen by the antibodies

Cells (really just some of them) The figure shows how red blood cell and thrombocytes (for blood-clot formation) derive from the same progenitor cells as the immune system. You don't have to memorize the details. Know B cells T cells (both types) and Macrophages (antigen presenting cells) like in the game.
Macrophage (big mouth). Know this one. Gobble pathogens up, present antigens to adaptive cells in the MHC receptor and release pro-inflammatory signal molecules (other antigen presenting cells include dendritic cells).
Weird-shaped nucleus cells (OK, that's not the official name. They are called "polymorphonuclear cells," which essentially means the same thing). They, along with mast cells, are the main source of the pro-inflammatory signals. They all have slightly different jobs and include the basophil (likes basic stain); neutrophil (neutral pH stain) and Eosinophil (likes acid stain). You wouldn't need to know what each of these do. But, you could get a figure that has them in it.

Mast Cells are probably the worst offender, along with basophils and eosinophils. Probably good to know Mast cells. They are the underlying inducers of allergies and anaphylaxis. Secrete lots of pro-inflammatory signals. Extra information: Eosinophils in particular collect special antibodies made by certain B cells called IgE, which they then use to attack all the multicellular parasites you have, like worms and such. If you don't have worms, they are fond of attacking pollen grains, etc.

Natural-killer (NK) cells. You should know these. Come from the same line as the cells of the adaptive immune system. Activated by macrophage signals, identify infected cells in the body and kill them

Adaptive Immunity

You should know all of this unless noted.
T-cells (thymus) and B-cells (bone-marrow).
B cells are the ones that make antibodies (also known as B-cell receptor prior to class switching).
Both T and B cells undergo "somatic rearrangement" of their DNA to express one and only one T-cell receptor or B-cell receptor. The enzymes that carry out the splicing of the DNA are called "Rag-1" and "Rag-2." (Recombination Activation Gene 1 and 2). This is known as "V(D)J recombination and it generates a different antibody
for each B cell line you have. A very similar thing happens in the T-cells. During maturation of B cells, one V (variable) region, one D region (diversity) and one J region (junctional) are brought together and linked to the Constant region to make the heavy chain of the antibody. The light leaves out the "D" and the C region.
The "antigen-combining site" is at the amino (NH2) terminus of each chain. This is what allows the antibody to bind the antigen.

Cytotoxic T-cells (also called "CD8-positive T cells") identify infected cells and other targets based on specific recognition by their T-cell receptor and secrete chemicals to kill them. They make their receptor through a similar process as the B cell (somatic recombination).

Helper T Cells
These are critical for the full response (and also the target of HIV. They have a T-cell receptor as does the killer. But, they look for B cells that have been stimulated by the same antigen. If they find one, they initiate the highly active response in the B cell in which the receptor evolves into an even more specific antibody. Eventually, the highly activated B cells undergo "class switching," which means they do an additional rearrangement in the DNA to remove the C-region that has the trans-membrane domain and replace it with a secretion signal and a soluble domain. It is then released as a soluble antibody.

The main use of the antibody is then to target components of the innate immunity more specifically toward the pathogen.

I think that's the important stuff. Remember, I sugar wcan show you figures of things I haven't discussed, necessarily. Also, go over the terminology on the online quiz.

Evolution links

Essay about the controversy in Science
Nasty Dawkins diatribe
Examples of coopertivity
Wiki on group selection
Pinker Essay
DS Wilson article for counterpoint to Pinker
E.O. Wilson paper from 2005 that starts this mess


Epigenetics. Or, how do you change DNA without changing DNA?

OK. That was too clever. What I mean is, how do cells permanently become determined to do only a subset of things without changing the DNA sequences?
We know that Immune cells actually do change some of their DNA sequence. But, that's really unusual. When epithelial cell divides, the two daughter cells "know" they are epithelial cells. This comes down to changes in how the DNA is packed and arranged in the nucleus. Whole regions of chromosomes are tightly packed in what we call "heterochromatin," which is differentiated from open "euchromatin," and is not actively transcribed.
Moreover, some of the changes are more subtle than that, but still maintained as the cells divide. So, the questions are:
  1. what are these stable "marks" on the DNA?
  2. How are they maintained?
  3. How are they removed?

That last one is really important. Because we know how that works, we now can convert adult cells into "Induced Pluripotent Stem Cells," IPSCs, which can do any job.

The answer to the first question basically is:
  1. there are changes made to the non-base-pairing sections of the DNA bases, usually addition of methyl groups at Cs in "CpG" islands
  2. additions of methyl groups to the proteins that pack the DNA (histones)
  3. there are added acetyl and phosphate groups added to the proteins, which tend to "open up" the DNA.

  1. The first two generally close down the DNA and make it less accessible to transcription.


These are maintained by enzymes such as these:

which read the status of the DNA after replication and re-establish it. So, if these enzymes find that one strand of DNA has methyl groups on the 5'-C-p-G sequence (that would be the template or "old" strand), they put methyl groups on the other stand (which would also be 5'-C-p-G)


The answer to the last question is that there are transcription factors that, when induced, will turn on a battery of genes that "scrub" the marks off all the DNA and histones, essentially rendering the cells back to the default, pluripotent state. How would you go looking for them? As we discussed, the experiment that worked was to transfer genes from embryonic stem (ES) cells to ordinary cells and see if you can find genes that induce the ordinary cells to become more ES like. The method here is a bit more difficult than the "transfer of genetic material" expeiment we did. But, the idea is the same. They used a viral system to "transduce" genes. Originally, 8 different genes were found to be needed. Since then, it seems you can pare down that number to 2 or 3 genes (which often then induce the other 5 or 6).
After that, scientists did experiments in which they knocked out one or more of the genes they determined were needed to either induce or maintain the "mark-free" state, often finding that th embryos would differentiate prematurely into a "trophoblast." Basically, these are the first differentiated cells in an embryo and are technically never going to be part of the developing organism. they form the support cells around the embryo and, in placental mammals, form the embryo side of the placenta.
This result adds support for the idea that the genes are involved in establishing or maintaining the "pluripotent" state.
You might like the relatively short wikipedia article on IPSCs, which is found here.