spring2018 week1

This commit is contained in:
ackman678
2018-04-11 12:51:49 -07:00
parent c933bf3625
commit b3f05472d2
5 changed files with 557 additions and 593 deletions

View File

@@ -1,34 +1,49 @@
## What is neuroscience?
# What is neuroscience?
Neuroscience is a field of scientific study that seeks to understand how the nervous system carries out its functions and what goes wrong when it doesnt.
Neuroscience is a field of scientific study that seeks to understand how the nervous system carries out its functions and what goes wrong when it doesnt.
While humankind has learned alot about nervous system structure and function, there is a great deal left to understand. It's up to you to figure it all out.
<img src="figs/human-brain.svg" height="300px">
http://courses.pbsci.ucsc.edu/mcdb/bio125/
https://courses.pbsci.ucsc.edu/mcdb/bio125/
Note:
Welcome. This class will be an Introduction to Neuroscience Neuroscience is a field that by necessity integrates information and techniques from many other scientific disciplines— not just biological sciences like genetics, molecular biology, biochemistry, immunology, physiology. But also physics, engineering, computer science, psychology. And these days neuroscience is touching upon fields as varied as sociology, criminology, marketing, ethics, and the law. So what is Neuroscience? Neuroscience is fundamentally a field that...
Welcome. This class will be an Introduction to Neuroscience
Neuroscience is a field that by necessity integrates information and techniques from many other scientific disciplines— not just biological sciences like genetics, molecular biology, biochemistry, immunology, physiology. But also physics, engineering, computer science, psychology. And these days neuroscience is touching upon fields as varied as sociology, criminology, marketing, ethics, and the law. So what is Neuroscience? Neuroscience is fundamentally a field that...
And ultimately it is a field of science that seeks to understand how this lump of biological tissue siting inside our heads has evolved the capability of asking questions about its own nature and existence.
While humankind has learned alot about nervous system structure and function, there is a great deal left to understand. It's up to you to figure it all out.
Thus it will be you, and your children, and your childrens children that will figure it all out and literally allow human beings to reach the stars.
--
## Syllabus and text book
<div style="width:700px; padding:25px 0; float:left;"><a href="https://courses.pbsci.ucsc.edu/mcdb/bio125/">https://courses.pbsci.ucsc.edu/mcdb/bio125/</a></div>
<div style="width:250px; float:left;"><img src="figs/ScreenShot2016-01-04at3.59.29PM_dea1077.png" height="200px"><figcaption></figcaption></div>
--
## Permission code requests
Just send me an email with the following subject line and body:
Just send me an email.
**subject line:**
```txt
permission code request biol 125
permission code request: #biol125
```
**body:**
```txt
ID#:
NAME: *First Middle Last*
EMAIL:
REASON YOU CANNOT ENROLL:
Id: 1234567
Name: First Last
Email: cruzid@ucsc.edu
Reason you cannot enroll: Brief description (one line).
```
--
@@ -39,9 +54,12 @@ REASON YOU CANNOT ENROLL:
* Menu: `m`
* Fullscreen: `f`
* Overview: `o` or `esc`
* Notes: `s`
* Zoom: `alt-click` or two-finger multi-touch (touch screens/trackpads)
* Zoom-scroll: two-finger drag (touch screens/trackpads while zoomed in)
* Print: `...lecture.html?print-pdf`
<!-- * Print: `...neuroanatomy1.html?print-pdf` -->
Recommend browser is Chrome on a laptop/PC. Some features that only have keyboard bindings (e.g. fullscreen, overview) may not work or be disabled on tablet/touch screen devices.
@@ -49,14 +67,14 @@ Recommend browser is Chrome on a laptop/PC. Some features that only have keyboar
## What are the nervous systems functions?
* The nervous system organizes and controls an individuals appropriate interactions with the environment
* Thus, its functions are dynamic, vast and wide-ranging extending to include all thoughts, perceptions, bodily actions, behaviors, and even the very essence of ones being: consciousness and the mind
* The nervous system organizes and controls an individuals appropriate interactions with the environment <!-- .element: class="fragment fade-in" data-fragment-index="1"-->
* Its functions are dynamic, vast and wide-ranging extending to include all thoughts, perceptions, bodily actions, behaviors, and even the very essence of ones being: consciousness and the mind <!-- .element: class="fragment fade-in" data-fragment-index="2"-->
Note:
What does the nervous system do? It organizes and controls an individuals interactions with the environment. It does this by processing current or past experiential information and making and executing behavioral decisions.
Therefore the brains functions are dynamic, vast and wide ranging, and extends to include all thoughts, perceptions, and actions and the very core of what it means for each of one us to be us consciousness and the mind. It is this complex lump of biological tissue, this emergent computational system that allows us humans to not only imagine the future, but to create it as well.
Therefore the brains functions are dynamic, vast and wide ranging, and extends to include all thoughts, perceptions, and actions and the very core of what it means for each of one us to be us consciousness and the mind. It is this complex lump of biological tissue, this emergent computational system that allows us humans to not only imagine the future, but to create it as well.
--
@@ -64,7 +82,7 @@ Therefore the brains functions are dynamic, vast and wide ranging, and extend
<div><img src="figs/From_the_Earth_to_the_Moon_Jules_Verne_695f816.jpg" height="200px"><figcaption>J. Verne, 1865</figcaption></div>
<!--
<!--
<div><img src="figs/2015-06-22_15.39.40_7af33ea.png" height="200px"><figcaption>Edgar Rice Burroughs, 1912</figcaption></div>
<div><img src="figs/Do_androids_dream_of_electric_sheep_1968_2a4fe82.jpg" height="200px"><figcaption>Philip K. Dick, 1968</figcaption></div>
<div><img src="figs/The_forever_war_1974_1be2645.png" height="200px"><figcaption>Joe Haldeman, 1974</figcaption></div>
@@ -74,9 +92,9 @@ Therefore the brains functions are dynamic, vast and wide ranging, and extend
Note:
Ever since the dawn of the industrial age in the mid 19th century and Jules Verne's 1865 novel 'From the Earth to the Moon' humans have been dreaming of the future, not just here but among the stars. And those futures can become reality like when the Apollo astronauts landed on the moon and acknowledged the inspiration that Verne's orig sci-fi novel had on many.
Ever since the dawn of the industrial age in the mid 19th century and Jules Verne's 1865 novel 'From the Earth to the Moon' humans have been dreaming of the future, not just here but among the stars. And those futures can become reality like when the Apollo astronauts landed on the moon and acknowledged the inspiration that Verne's orig sci-fi novel had on many.
Neuroscience and its role for proper physiological function is going to play a role in many advances in health and technology for humankind now and far into the future--
Neuroscience and its role for proper physiological function is going to play a role in many advances in health and technology for humankind now and far into the future--
To reach the stars we will need:
@@ -102,7 +120,6 @@ The human brain and its limitless creativity has packed a bunch of computational
Since that time we've dreamed up fantastical futures in shows like Star Trek and the Jetsons and dystopian ones in Blade Runner and the Terminator or even ones past (for example think "long time ago in a galaxy far far away...")
Many of things dreamed of are already presentImagine some of things thought of and now already present flying aeroplanes, personal landspeeders, rocket ships to distant planets
\
- Edgar Rice Burroughs John Carter thought waves example.
@@ -118,25 +135,23 @@ Penfield mood organ
* The patterns of connections between nerve cells
* The relationship of different patterns of interconnections to different types of behavior
<div style="width:700px; padding:25px 0; float:left;"><a href="http://courses.pbsci.ucsc.edu/mcdb/bio125/">http://courses.pbsci.ucsc.edu/mcdb/bio125/</a></div>
<div style="width:250px; float:left;"><img src="figs/ScreenShot2016-01-04at3.59.29PM_dea1077.png" height="100px"><figcaption></figcaption></div>
Note:
Nervous
: relating to or affecting the nerves
Nervous
: relating to or affecting the nerves
nervosus
: latin
: sinewy, vigorous
nervosus
: latin
: sinewy, vigorous
nervus
: latin
: sinew
nervus
: latin
: sinew
sinew
: fibrous tissue linking bone or muscle to bone
: the parts of a structure, system, or thing that give it strength or bind it together
sinew
: fibrous tissue linking bone or muscle to bone
: the parts of a structure, system, or thing that give it strength or bind it together
@@ -147,14 +162,15 @@ sinew
<div style="font-size:0.9em">
<div></div>
* We are now in a gene-centric “post-genomic” phase of neuroscience
* Many genes are expressed in the brain, either during development or in the adult. It is the spatial and temporal regulation of these genes and an organisms interaction with the environment that builds a nervous system.
* Neuroscience therefore encompasses many fields, including genetics, cell biology, physiology, and development biology.
* Many genes are expressed in the brain, either during development or in the adult. It is the spatial and temporal regulation of these genes together with an organism's interaction with the environment that builds a nervous system.
* "nature <del style="color:red">OR</del> **AND** nurture"
</div>
Note:
* Neuroscience encompasses many fields: genetics, molecular and cell biology, developmental biology, physiology.
- not nature or nurture, nature and nurture
- language, learning to ride a bike
- clones, identical twins
@@ -167,23 +183,24 @@ Note:
<div></div>
organism | # of genes | # of base pairs | # of neurons | development time (young adult)
---------- | ---------- | --- | ------------ | -------------------------
*Caenorhabditis elegans* (nematode) | ~19,000 | ~97 million | 302 | 8 hrs
---------- | ---------- | --- | ------------ | -------------------------
*Caenorhabditis elegans* (nematode) | ~19,000 | ~97 million | 302 | 8 hrs
*Drosophila melanogaster* (fruit fly) | ~15,000 | ~120 million | ~250,000 | 711 days
*Danio rerio* (zebrafish) | ~24,000 | ~1.5 billion | ~10,000,000 | 30 days
Mouse | ~25,000 | ~3.5 billion | ~71,000,000 | 2-3 months
Human | ~20,000 | ~3.5 billion | ~100,000,000,000 | 18 years
African elephant | ~20,000 | ~3.1 billion | ~267,000,000,000 | 18 years
Mouse | ~25,000 | ~3.5 billion | ~71,000,000 | 2-3 months
Human | ~20,000 | ~3.5 billion | ~100,000,000,000 | 18 years
African elephant | ~20,000 | ~3.1 billion | ~267,000,000,000 | 18 years
</div>
<figcaption>see also Neuroscience 5e Box 01A</figcaption>
<!-- <figure><img src="figs/Neurscience5e-Box-01A-0_0eadd2b.jpg" height="100px"><figcaption></figcaption></figure> -->
Note:
Number of genes is not related to nervous system complexity or size. The nematode c. elegans has just 302 neurons, and yet its genome contains virtually as many genes as a humans. An african elephant brain weighs 3 times more than a human brain and has 3 times the number of neurons.
Number of genes is not related to nervous system complexity or size. The nematode c. elegans has just 302 neurons, and yet its genome contains virtually as many genes as a humans. An african elephant brain weighs 3 times more than a human brain and has 3 times the number of neurons.
Even number of base pairs: Paris japonica has 150 billion base pairs of DNA (50x larger than that of a human haploid genome)
Even number of base pairs: Paris japonica (white, star like flower) has 150 billion base pairs of DNA (50x larger than that of a human haploid genome)
The largest brains are those of sperm whales, weighing about 8 kg (18 lb). An elephant's brain weighs just over 5 kg (11 lb), a bottlenose dolphin's 1.5 to 1.7 kg (3.3 to 3.7 lb), whereas a human brain is around 1.3 to 1.5 kg (2.9 to 3.3 lb). Brain size tends to vary according to body size.
@@ -195,7 +212,20 @@ The largest brains are those of sperm whales, weighing about 8 kg (18 lb). An el
## There are many brain-specific and non-brain specific genes expressed in the nervous system
<figure><img src="figs/Neuroscience5e-Fig-01.01-1R_7806e74.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 1.1</figcaption></figure>
<!-- <figure><img src="figs/Neuroscience5e-Fig-01.01-1R_7806e74.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 1.1</figcaption></figure> -->
<div>
<div></div>
| tissue | Number of expressed genes |
| --- | --- |
| brain only | ~6000 |
| brain & all other tissues | ~8000 |
| other tissues only | ~6000 |
| | total: 20000 |
<figcaption>see also Neuroscience 5e Fig. 1.1</figcaption>
</div>
Note:
@@ -206,158 +236,23 @@ Out of those 20000 genes, there are many expressed genes that are common between
## A single mutation can lead to dramatic brain size defects
Mutation in a spindle pole gene call ASPM1
Mutation in a spindle pole gene call ASPM1 (altered mitosis during brain development)
<!-- <figure><img src="figs/Neuroscience5e-Fig-01.01-3R_562abf7.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 1.1</figcaption></figure> -->
<figure><img src="figs/Bond-natgenet2002-fig1.jpg" height="350px"><figcaption>[Bond:2002](https://dx.doi.org/10.1038/ng995), see also Neuroscience 5e Fig. 1.1</figcaption></figure>
<figure><img src="figs/Neuroscience5e-Fig-01.01-3R_562abf7.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 1.1</figcaption></figure>
Note:
Now mutations in single genes in the right place in our genome can cause drastic effects on the formation of our brains wiring.
Now mutations in single genes in the right place in our genome can cause drastic effects on the formation of our brains wiring.
For example, shown here is a person with a mutation in ASPM1 a protein used to make spindle poles for mitotic stem cells during embryonic development.
But most single gene mutations do not cause such drastic effects, with a more subtle and complex set of genetic and environmental risk factors causing neurological disease, similar to and probably exceeding the complex etiology of cancer.
---
## Model organisms— C. elegans
* It is hard to visualize and monitor neurons and manipulate genes in humans so neuroscientists study a number of different organisms
* The nematode worm *C. elegans* is great for genetic engineering and has a tiny nervous system (just 302 neurons)
<div><img src="figs/Adult_Caenorhabditis_elegans_d76c553.jpg" height="150px" title="CC from wikipedia https://commons.wikimedia.org/w/index.php?curid=2680458"><figcaption>C. elegans commons.wikimedia.org/w/index.php?curid=2680458</figcaption></div>
<div><img src="figs/c-elegans-connectome_2_9548c95.jpg" height="150px"><figcaption>C. elegans wiring diagram [openworm.org](http://www.openworm.org), neuroconstruct.org</figcaption></div>
Note:
Now to do neuroscience research we have to use model organisms of course. Small number of neurons, can be labeled using green fluorescent protein or other means.
C. elegans is a nematode or roundworm. It is non-infectious and non-parasitic organism just 1 mm long and it can be easily genetically engineered. That means you can introduce mutations to genes or express fancy inert proteins that allow you to track the function of genes and cells in living animals making it a great model organism.
For neuroscientists it has only 302 total neurons making it a great way to dissect neural circuits underlying simple behaviors. Many mutant worms have been isolated that affect nervous system function allowing us to learn about the function of those genes. And you can engineer the worms to express fluorescent proteins so that the animal's neurons glow under a microscope. How many of you have heard of green fluorescent protein?
Having just 302 neurons is great for for some types of studies, however we have more than a million neurons in each of our eyes just alone
More than 1 million neurons that just form the optic nerve from each of our eyes!
---
## Model organisms— squid
Squids have unusually large axons (1 mm diameter)
<div style="width:250px; float:left;"><img src="figs/20000_squid_holding_sailor_f98a242.jpg" height="300px"><figcaption>20000 Lieues Sous les Mers, J. Verne</figcaption></div>
<div style="width:500px; float:left;"><img src="figs/Squid_Loligo_pealei_cbafe46.jpg" height="300px"><figcaption>Atlantic squid, *Loligo pealei*</figcaption></div>
<!-- <div><img src="figs/axon_large_9a8a930.jpg" height="300px"><figcaption>Squid giant axon, R. Hanlon MBL Woods Hole</figcaption></div> -->
Note:
Jules Verne provided inspiration for the space age but also neuroscientists in the 1940s.
Squids are arguably the most important model organism in the history of neuroscience. They are rarely studied anymore but their large axons which are 1mm in diameter-- 1000x bigger than our axons-- made their axons amenable to sticking electrodes inside them in the 1930s-50s and allowed neuroscientist to discover the biophysical and mathematical basis of neuronal signaling. We will discuss squid giant axons in much more detail soon.
Other important invertebrate organisms in neuroscience research include sea slugs and fruit flies and zebrafish. Some of these are very amenable to genetic engineering like C. elegans and have nervous systems more similar to our own.
Phylum: Mollusca
Class: Cephalopoda
Order: Teuthida
Family: Loliginidae
Genus: Loligo
Atlantic squid (Loligo pealei)
Phylum: Mollusca
Class: Cephalopoda
Order: Sepiida
Family: Sepiidae
Genus: Sepia
---
## Model organisms— Mus. musculus
The mouse is a common model in neuroscience research.
<div style="width:225px; float:left;"><img src="figs/adult_mouse_jax_ec76ad4.jpg" height="200px"><figcaption>Common house mouse *Mus. musculus*, jax.org</figcaption></div>
<div style="width:300px; float:left;"><img src="figs/abi_adult_mouse_brain_e79e400.jpg" height="200px"><figcaption>Mouse brain 3D rendering, [Brain Explorer 2](http://mouse.brain-map.org/static/brainexplorer)</figcaption></div>
<div style="width:430px; float:left;"><iframe src="https://www.youtube.com/embed/stPThgZ2Y5o" width="420" height="315"></iframe><figcaption>Green fluorescent protein (GFP) labeled neurons inside a mouse brain</figcaption></div>
Note:
But mammals are the only animals that have evolved a convoluted superficial part of the brain called the neocortex. And it is the cerebral neocortex is crucial for our highest cognitive functions, even if it sometimes seems that in election years that humans have lost their cerebral function.
Thus for research pertaining to the structure and function of the mammalian brain and human disease we turn to rodents like the common house mouse. Mice are small with a brain 2 cm in length, develop fairly quickly, and their genome has long been one of the most amenable to genetic engineering though this is quickly changing newer molecular biology techniques (like the CRISPR/Cas9 system).
* Mouse brain is about 2 cm in length
* genetically tractable
* [https://www.youtube.com/watch?v=stPThgZ2Y5o](https://www.youtube.com/watch?v=stPThgZ2Y5o)
---
## Model organisms other mammals
Higher mammals are used to study more complex brain functions.
<div><img src="figs/1f412_3fc8278.svg" height="200px"><figcaption>Cats visual system function, locomotion</figcaption></div>
<div><img src="figs/1f412_f738dec.svg" height="200px">
<figcaption>
Non-human primates attention, decision
making, vision, brain machine interfaces
</figcaption></div>
<div><iframe src="https://www.youtube.com/embed/UJ_rFMYDbAE" width="420" height="315"></iframe><figcaption>Rhesus monkey mind controlled wheelchair</figcaption></div>
<!--
<div style="float:left;"><figure style="display:inline-table;"><img src="figs/1f412_3fc8278.svg" height="200px"><figcaption style="display:table-caption; caption-side:bottom;">Cats visual system function, locomotion</figcaption></figure></div>
<div style="float:left;"><figure style="display:inline-table;"><img src="figs/1f412_f738dec.svg" height="200px"><figcaption style="display:table-caption; caption-side:bottom;">Non-human primates attention, decision making, vision, brain machine interfaces</figcaption></figure></div>
<div style="width:430px; float:left;"><iframe src="https://www.youtube.com/embed/L2O58QfObus" width="420" height="315"></iframe><figcaption>Rhesus monkey mind controlled wheelchair</figcaption></div>
-->
Note:
Research with cats was critical for work from the 1950s to 1980s that allowed neuroscientist to learn how visual signals are processed in the highest circuits of the mammalian brain.
And research with rhesus monkeys has been essential for learning about perceptual, attentional, and decision making in the mammalian brain together with research into brain-machine interfaces that have direct clinical applications for human patients.
3rs: Replacement, Reduction, and Refinement
---
## Brain lesion patients
* Lesions in brains or degenerative diseases help us understand brain function
* Phineas Gage Railroad spike through frontal lobes changed his personality
<div><img src="figs/image7_0e1af20.png" height="200px"><figcaption></figcaption></div>
<div><img src="figs/image8_c3232ea.png" height="200px"><figcaption></figcaption></div>
Note:
Furthermore, studies of patients with brain lesions has historically been key to localizing parts of the brain that affect emotional states and learning and memory.
e.g. Phineas Gage in 1848 his whole personality changed after the spike went through his brain.
Harlow wrote: "the equilibrium... between his intellectual faculties and his animal propensities seems to have been destroyed"
2cm scale bar. left 13yr old female patient. right 11 yr old control.
---
@@ -371,7 +266,7 @@ A glob of squishy jello? <!-- .element: class="fragment strike" data-fragment-in
<figure class="fragment fade-in" data-fragment-index="1"><img src="figs/image11_fbb6fc7.png" height="100px"><figcaption>Wikimedia Commons</figcaption></figure>
Cells. <!-- .element: class="fragment fade-in" data-fragment-index="1"-->
Cells. (though jello is made of collagen...) <!-- .element: class="fragment fade-in" data-fragment-index="1"-->
Note:
@@ -399,9 +294,9 @@ Only after fundamental and rigorous work by these two scientists, C. Golgi and S
Golgi staining: potassium chromate and silver nitrate (1873)
<div><img src="figs/camillo_golgi_hippocampus_40b7a67.jpg" height="300px"><figcaption>Golgi's drawing of the hippocampus impregnated by his stain (from Golgi's Opera Omnia).</figcaption></div>
<div><figcaption class="big">Golgi's drawing of the hippocampus impregnated by his stain</figcaption><img src="figs/camillo_golgi_hippocampus_40b7a67.jpg" height="300px"><figcaption>from Golgi's Opera Omnia.</figcaption></div>
<div><img src="figs/golgi_nobel_lecture_fig9_eb014b5.png" height="300px"><figcaption>Golgi's drawing of hippocampal dentate gyrus, fig. 9 from Nobel lecture</figcaption></div>
<div><figcaption class="big">Golgi's drawing of hippocampal dentate gyrus</figcaption><img src="figs/golgi_nobel_lecture_fig9_eb014b5.png" height="300px"><figcaption>fig. 9 from Golgi's Nobel lecture</figcaption></div>
Note:
@@ -414,7 +309,7 @@ Golgi's drawing of hippocampus after performing his black potassum chromate and
* syncytium: a mass of cytoplasm with many nuclei but no internal cell boundries
* reticulum: a fine network or netlike structure
* Camillo Golgi, Nobel Lecture December 11, 1906, *The Neuron Doctrine- theory and facts*:
* Camillo Golgi, Nobel Lecture December 11, 1906, *The Neuron Doctrine- theory and facts*:
<div style="width:960px; font-size:0.6em">
<div></div>
@@ -440,11 +335,11 @@ Golgi drew the structure of the hippocampus as being all fused together into a r
Note:
Neurons in culture have specific endings. EM methods, dye filling experiments.
Neurons in culture have specific endings. EM methods, dye filling experiments.
Heinrich Wilhelm Gottfried von Waldeyer-Hartz (6 October 1836 23 January 1921) was a German anatomist and conceived the word 'neuron'.
Golgi in his nobel lecture:
Golgi in his nobel lecture:
>(3) The neuron is a physiological unit. This fundamental idea which Waldeyer
expressed with perfect precision has been enlarged upon both from
anatomical and functional sides with additional propositions, for example :
@@ -460,17 +355,17 @@ also trophic units.**
<div style="width:300px; float:left;"><img src="figs/CamilloGolgi_5c05797.jpg" height="200px"><figcaption class="big">
Camillo Golgi
Pavia University
Pavia, Italy
Camillo Golgi
Pavia University
Pavia, Italy
</figcaption></div>
<div style="width:600px; float:left;"><img src="figs/SantiagoRamonyCajal_dd682a4.jpg" height="200px"><figcaption class="big">
Santiago Ramón y Cajal
Madrid University
Madrid, Spain
Santiago Ramón y Cajal
Madrid University
Madrid, Spain
</figcaption></div>
@@ -509,7 +404,7 @@ Now there are two basic cell types in the nervous system, neurons and glia. We w
Up to 90% of brain cells in mammals.
During evolution the glia/neuron ratio basically follows a power relation ship [^Herculano-Houzel-2014] y(x) = kx^n where on a log-log plot k is the intercept and n is the slope. Some of this original comparative estimates of glia/neuron ratios among animals was performed by Friede (1954)
During evolution the glia/neuron ratio basically follows a power relation ship [^Herculano-Houzel-2014] y(x) = kx^n where on a log-log plot k is the intercept and n is the slope. Some of this original comparative estimates of glia/neuron ratios among animals was performed by Friede (1954)
Perhaps only 10% of cells in invertebrates like drosophila.
@@ -573,13 +468,13 @@ Astrocytes are star shaped, hence their name.
Astrocytes are your pizza delivery persons for neurons. They are also like your mom, constantly upkeeping your room or synapses as is the case for neurons.
They are the direct decendents of the mother stem cells that give rise to the neurons and glia of the nervous system.
They are the direct decendents of the mother stem cells that give rise to the neurons and glia of the nervous system.
Devasting diseases of astrocyte function include brain cancer with gliomas like glioblastomas typicaly being comprised of astrocytes gone wild. It is also thought that some childhoold epilepsies may originate from altered astrocyte function.
blood brain barrier-- control entry of neurotransmitters and hormones into the brain
areas of the brain without a blood-brain barrier (from Table 32-2 Basic Neurochemistry 6e):
areas of the brain without a blood-brain barrier (from Table 32-2 Basic Neurochemistry 6e):
Pituitary gland
Median eminence
@@ -589,7 +484,7 @@ Paraphysis
Pineal gland
Endothelium of the choroid plexus
There is a positive relationship between lipid solubility and brain uptake of chemical compounds
There is a positive relationship between lipid solubility and brain uptake of chemical compounds
- permeability of lipid soluble compounds is rapid (ethanol, nicotine, diazepam, THC)
- polar molecules (e.g. glycine and catecholamines) enter slowly across BBB
@@ -617,7 +512,7 @@ water enters rapidly through diffusion.
<div style="width:300px; float:left;"><figcaption class="big">young oligodendrocyte</figcaption><img src="figs/Fig2d-oligodendrocyte_82ab0a3.png" height="150px"><figcaption>Ackman et al., 2006</figcaption></div>
<div style="width:450px; float:left;"><figcaption class="big">mature oligodendrocyte</figcaption><img src="figs/olig_9390c05.png" height="400px"><figcaption>J. Ackman 2005</figcaption></div>
<div style="width:350px; float:left;"><figcaption class="big">mature oligodendrocyte</figcaption><img src="figs/olig_9390c05.png" height="300px"><figcaption>J. Ackman 2005</figcaption></div>
Note:
@@ -673,7 +568,9 @@ Note:
## Cell body (soma) of a neuron
<figure><img src="figs/Neuroscience5e-Fig-01.03-1R_444117f.jpg" height="500px"><figcaption></figcaption></figure>
<!-- <figure><img src="figs/Neuroscience5e-Fig-01.03-1R_444117f.jpg" height="500px"><figcaption></figcaption></figure> -->
<figure><img src="figs/neuron-soma.svg" height="350px"><figcaption>[JA, CC0](https://creativecommons.org/share-your-work/public-domain/cc0/)</figcaption></figure>
Note:
@@ -691,23 +588,42 @@ Note:
<!-- <figure><img src="figs/neurons_9b62aa4.jpg" height="100px"><figcaption></figcaption></figure> -->
<figure><img src="figs/Neuroscience5e-Fig-01.02-1R-pyr-neuron_aa8d83c.jpg" height="300px"><figcaption></figcaption></figure>
<!-- <figure><img src="figs/Neuroscience5e-Fig-01.02-1R-pyr-neuron_aa8d83c.jpg" height="300px"><figcaption></figcaption></figure> -->
Note:
Polarity is everywhere in physics... and biology!
* electric dipole moments of molecules
* earth's magnetic poles
* electromagnetic waves
* DNA (5'-->3')
* mitotic cells
* apical-basal orientation of cells within tissues
* animal embryos and neural tube
from oxford dict,
polar
: directly opposite in character or tendency
polarity
: the relative orientation of poles; the direction of a magnetic or electric field
: the tendency of organisms or parts to develop with distinct anterior or posterior ends, or to grow or orient in a particular direction
---
## Structures of a neuron
* cell body (soma) metabolic center of the cell, contains the nucleus.
* dendrites receive incoming signals from other nerve cells
* axon carries signals to other neurons
* axon hillock initiates action potentials
* synapse site at which two neurons communicate
* synaptic cleft area between pre and post-synaptic cell
* Cell body (soma) metabolic center of the cell, contains the nucleus.
* Dendrites receive incoming signals from other nerve cells
* Axon carries signals to other neurons
* Axon hillock initiates action potentials
* Synapse site at which two neurons communicate
* Synaptic cleft area between pre and post-synaptic cell
Note:
@@ -716,7 +632,7 @@ Note:
## Neuron processes: dendrites
* Dendrites
* Dendrites
* Extensively branching from the cell body
* Transmit electrical signals (graded potentials) toward the cell body
* Function as receptive sites for other neurons
@@ -729,15 +645,15 @@ Note:
## Dendritic spines
<div style="width:400px; float:left;"><figcaption class="big">Purkinje neuron</figcaption><img src="figs/denk_1995-purkinje_neuron_5316809.jpg" width="350px"><figcaption>Denk et al., 1995</figcaption></div>
<div style="width:400px; float:left;"><figcaption class="big">Purkinje neuron dendritic tree</figcaption><img src="figs/denk_1995-purkinje_neuron_5316809.jpg" width="350px"><figcaption>Denk et al., 1995</figcaption></div>
<div style="width:550px; float:left;"><figcaption class="big">CA1 pyramidal neuron</figcaption><img src="figs/Tonnesen2014_nn.3682-SF1_56795be.jpg" height="500px"><figcaption>Tønnesen et al., 2014. 500 nm scale</figcaption></div>
<div style="width:550px; float:left;"><figcaption class="big">CA1 pyramidal neuron dendrite and spines</figcaption><img src="figs/Tonnesen2014_nn.3682-SF1_56795be.jpg" height="400px"><figcaption>Tønnesen et al., 2014. 500 nm scale</figcaption></div>
Note:
* 2 billion transistors in an iphone6.
* 100 billion neurons, each receiving up to 10000 synaptic connections
* 100 billion neurons, each receiving up to 10000 synaptic connections
* quadrillion synapses, 10^15 in our nervous system
False color of the dendrite of one neuron near an axon from another neuron from an EM image
@@ -780,24 +696,8 @@ Note:
* Axon collaterals
* Multiple branches at end of axon
* Terminal branches
* End in knobs called axon terminals (also called end bulbs or boutons)
---
## Neuron signals: action potentials
* Nerve impulse (action potential or 'spike')
* Neuron receives and sends signals
* Generated at the initial segment of the axon
* Conducted along the axon
* Releases neurotransmitters at axon terminals
* Neurotransmitters excite or inhibit neurons
Note:
We will be discussing the nature of basic unit of nervous conduction, the action potential or impulse in great detail in ensuing lectures.
* Terminal branches
* End in knobs called axon terminals (also called terminal boutons)
---
@@ -815,7 +715,7 @@ Note:
## Example morphologies cerebellar neurons
<figure><figcaption class="big">Purkinje cell, cerebellum</figcaption><img src="figs/Neuroscience5e-Fig-01.02-3R-purkinje-neuron_688ca6e.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 1.2</figcaption></figure>
<figure><figcaption class="big">Purkinje cell, cerebellum</figcaption><img src="figs/Neuroscience5e-Fig-01.02-3R-purkinje-neuron_688ca6e.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 1.2</figcaption></figure>
Note:
@@ -824,14 +724,17 @@ Note:
## Example morphologies cortical neurons
* Pyramidal neurons multipolar neurons that contain both apical and basal dendrite. Also contain one axon.
* Pyramidal neurons multipolar neurons that contain both apical and basal dendrites. Also contain one axon eminating from cell body
* Most common excitatory neuron in the cerebral cortex
<div style="width:250px; float:left;"><figcaption class="big">pyramidal neuron</figcaption><img src="figs/Neuroscience5e-Fig-01.02-1R-pyr-neuron_aa8d83c.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 1.2</figcaption></div>
<!-- <div style="width:250px; float:left;"><figcaption class="big">pyramidal neuron</figcaption><img src="figs/Neuroscience5e-Fig-01.02-1R-pyr-neuron_aa8d83c.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 1.2</figcaption></div> -->
<div style="width:300px; float:left;"><figcaption class="big">pyramidal neurons</figcaption><img src="figs/golgi-pyr-neurons-fig19-nobel-lecture_b94e6d1.png" height="400px"><figcaption>C. Golgi, Fig. 19 Nobel lecture</figcaption></div>
<div style="width:250px; float:left;"><figcaption class="big">pyramidal neuron</figcaption><img src="figs/pyramidal-neuron.svg" height="300px"><figcaption>[JA, CC0](https://creativecommons.org/share-your-work/public-domain/cc0/). see also Neuroscience 5e Fig. 1.2</figcaption></div>
<div style="width:400px; float:left;"><figcaption class="big">rat pyramidal neuron</figcaption><img src="figs/071030_03_vc0110-2_lay2_biocy_zproj-merge_66b7de1.png" height="400px"><figcaption>Ackman et al., 2009</figcaption></div>
<div style="width:300px; float:left;"><figcaption class="big">pyramidal neurons</figcaption><img src="figs/golgi-pyr-neurons-fig19-nobel-lecture_b94e6d1.png" height="300px"><figcaption>C. Golgi, Fig. 19 Nobel lecture</figcaption></div>
<div style="width:400px; float:left;"><figcaption class="big">rat pyramidal neuron</figcaption><img src="figs/071030_03_vc0110-2_lay2_biocy_zproj-merge_66b7de1.png" height="300px"><figcaption>Ackman et al., 2009</figcaption></div>
Note:
@@ -856,9 +759,12 @@ Note:
## Structure of a sensory neuron (afferent)
Function of an **afferent** neuron is to carry information from the sensory periphery towards the CNS or brain.
Function of an **afferent** neuron is to carry information from the sensory periphery towards the central nervous system.
<!-- <figure><figcaption class="big">nociceptive (pain) neuron</figcaption><img src="figs/image28_d35899e.png" height="400px"><figcaption></figcaption></figure> -->
<figure><figcaption class="big">sensory neuron</figcaption><img src="figs/sensory-neuron.svg"><figcaption>[JA, CC0](https://creativecommons.org/share-your-work/public-domain/cc0/)</figcaption></figure>
<figure><figcaption class="big">nociceptive (pain) neuron</figcaption><img src="figs/image28_d35899e.png" height="400px"><figcaption></figcaption></figure>
Note:
@@ -868,9 +774,12 @@ Afferent- term meaning to send information from periphery to the CNS or to brain
## Structure of a motor neuron (efferent)
Function of an **efferent** neuron is to carry information towards the muscles for effecting behavior.
Function of an **efferent** neuron is to carry information towards the muscles for bringing about behavior.
<!-- <figure><figcaption class="big">alpha motor neuron</figcaption><img src="figs/image29_df57dca.png" height="400px"><figcaption></figcaption></figure> -->
<figure><figcaption class="big">motor neuron</figcaption><img src="figs/motor-neuron.svg"><figcaption>[JA, CC0](https://creativecommons.org/share-your-work/public-domain/cc0/)</figcaption></figure>
<figure><figcaption class="big">alpha motor neuron</figcaption><img src="figs/image29_df57dca.png" height="400px"><figcaption></figcaption></figure>
Note:
@@ -895,12 +804,31 @@ Note:
## Inter-neuronal signaling occurs at synapses
<figure><img src="figs/image30_268faa4.png" height="400px"><figcaption></figcaption></figure>
<!-- <figure><img src="figs/image30_268faa4.png" height="400px"><figcaption></figcaption></figure> -->
<figure><img src="figs/synapse-model.svg" height="350px"><figcaption>JA, CC0</figcaption></figure>
Note:
We will be going into synapse structure and function in much detail later in the class, but just to complete our introduction to basic anatomical details of neurons this figure illustrates...
We will be going into synapse structure and function in much detail later in the class, but just to complete our introduction to basic anatomical details of neurons this figure illustrates...
---
## Neuron signals: action potentials
* Nerve impulse (action potential or 'spike')
* Neuron receives and sends signals
* Generated at the initial segment of the axon
* Conducted along the axon
* Releases neurotransmitters at axon terminals
* Neurotransmitters excite or inhibit neurons
Note:
We will be discussing the nature of basic unit of nervous conduction, the action potential or impulse in great detail in ensuing lectures.
---
@@ -936,11 +864,14 @@ Note:
---
## Example of a simple circuit: stretch reflex (myotatic reflex)
## Example of a simple circuit: stretch (myotatic) reflex
The "knee-jerk response" is a simple reflex circuit.
<div style="width:100%; float:left;"><img src="figs/Neuroscience5e-Fig-01.07-1R-stretch-reflex-edit_c4d4d1a.jpg" width="700px"><figcaption>Neuroscience 5e Fig. 1.7</figcaption></div>
<!-- <div style="width:100%; float:left;"><img src="figs/Neuroscience5e-Fig-01.07-1R-stretch-reflex-edit_c4d4d1a.jpg" width="700px"><figcaption>Neuroscience 5e Fig. 1.7</figcaption></div> -->
<div style="width:100%; float:left;"><img src="figs/spinal-motor-reflex-arc.svg" height="350px"><figcaption>JA, CC0. see also Neuroscience 5e Fig. 1.7</figcaption></div>
<!-- <div style="width:250px; float:left;"><iframe src="https://www.youtube.com/embed/Ll8r5i0eaT8" height="150"></iframe><figcaption>Stretch reflex</figcaption></div> -->
@@ -960,7 +891,7 @@ Muscle lengthens, stretching muscle spindle (sensory ending), leading to incr al
## Ways to measure neural activity
* Extracellular recording an electrode is placed near a neuron. Measures action potentials. Useful for detecting patterns of activity.
* Extracellular recording an electrode is placed near a neuron. Measures action potentials. Useful for detecting patterns of activity.
* Intracellular recording an electrode is placed inside a neuron-can measure smaller graded potential changes. Useful for isolating responses to single inputs.
Note:
@@ -970,9 +901,11 @@ You might have the anatomy skills of Cajal or Golgi and you know there is this r
---
## Extracellularly recorded responses underlying the myotatic reflex
## Extracellularly recorded responses underlying the stretch reflex
<figure><figcaption class="big">Extracellular recordings showing action potential firing frequencies</figcaption><img src="figs/Neuroscience5e-Fig-01.08-0_080fe2c.png" width="700px"><figcaption>Neuroscience 5e Fig. 1.8</figcaption></figure>
<!-- <figure><figcaption class="big">Extracellular recordings showing action potential firing frequencies</figcaption><img src="figs/Neuroscience5e-Fig-01.08-0_080fe2c.png" width="700px"><figcaption>Neuroscience 5e Fig. 1.8</figcaption></figure> -->
<figure><figcaption class="big">Extracellular electrode recordings showing action potential firing frequencies</figcaption><img src="figs/spinal-motor-reflex-extracellular.svg" height="350px"><figcaption>CC0, see also Neuroscience 5e Fig. 1.8, 1.9</figcaption></figure>
Note:
@@ -980,17 +913,17 @@ Note:
These ticks are spikes or action potentials recorded extracelluarly. Since the electrode tip is placed close to the neurons cell membrane, the electrode can pick up signals as they pass by. A little bit like someone wiretapping your phone line.
---
We will come back to this reflex circuit in greater detail time and again as we go through this course.
And really, the basic logic of this circuit and variants of it is replicated all over the brain and teasing apart all the types of cells, their response properties, and their functional interactions or connections with one another for all types of different sensory and motor behavior is the grand challenge, beauty, and fun of modern and future neuroscience.
<!-- ---
## Intracellularly recorded reponses underlying the myotatic reflex
<figure><figcaption class="big">Intracellular recordings of neuronal responses in the reflex circuit</figcaption><img src="figs/Neuroscience5e-Fig-01.09-0_3d0b7b5.jpg" height="500px"><figcaption>Neuroscience 5e Fig. 1.9</figcaption></figure>
Note:
We will come back to this reflex circuit in greater detail time and again as we go through this course.
And really, the basic logic of this circuit and variants of it is replicated all over the brain and teasing apart all the types of cells, their response properties, and their functional interactions or connections with one another for all types of different sensory and motor behavior is the grand challenge, beauty, and fun of modern and future neuroscience.
---
And really, the basic logic of this circuit and variants of it is replicated all over the brain and teasing apart all the types of cells, their response properties, and their functional interactions or connections with one another for all types of different sensory and motor behavior is the grand challenge, beauty, and fun of modern and future neuroscience. -->