Historical Introduction
Purves et al., Chapter 1 and figures from Chapters 6 & 26 and Appendix
B
(there will also be a review that introduces you to the Sylvius CD)
(some of this is a review of "Bio 1" and "Cell biology")
Brain - ancient history
Hippocrates (460-379 BC), of "hippocratic oath" fame, understood
the influence of the brain in determining normal and abnormal functions,
emotions, learning, insanity.
Appendix B Fig. B17 (this human brain view shows cerebrum, cerebellum, ventricles)
Galen (AD 130-200) did careful dissections. He thought, from texture, that
the cerebrum was sensory and cerebellum was motor. This was remarkably (not
completely) correct, though for the wrong reasons. There was interest in
the ventricles (filled with cerebro-spinal fluid [CSF]), and this fit in
with belief in vital "humors."
Neuroanatomy terms:
Fig. 1.12A (view of exterior of human brain)
sulcus (plural=sulci) = fissure
For instance, central sulcus is major landmark
gyrus (plural=gyri) = convolution -> lobes (a larger area)
For instance, precentral gyrus is motor cortex
And postcentral gyrus is somatosensory (touch) cortex
Fig. 1.12C (colored view of exterior and mid-sagittal section of human brain)
Emphasis is on "localization of function" in different lobes
For instance, occipital lobe is where vision projects
And Temporal lobe is where audition projects
just to put into perspective the degree to which much of this information
is background,
TRANSPARENCY shows the version of this picture the Biology Department teaches
to freshmen
CNS = central nervous system (brain and spinal cord)
PNS = peripheral nervous system
Fig. 1.12D (human brain drawing showing coronal sections, to reveal basal
ganglia)
Fig. 1.12E&F shows the coronal sections indicated
white matter, bundles of myelinated axons (Tracts in CNS, Nerve in PNS)
[misnomer - optic "nerve," second cranial nerve, is actually a
tract since retina and optic nerve are considered part of the CNS on embryological
grounds]
and
gray matter (Nuclei in CNS, Ganglia in PNS)
[misnomers - basal ganglia are nuclei and ganglion cells in retina]
Fig 1.9 (cross section of human spinal cord)
white matter and gray matter
(nerve connections to and in the spinal cord)
Nerve (peripheral nervous system [PNS])
Tract (central nervous system [CNS])
Fig. 1.7 (diagram of knee jerk reflex)
Afferent (toward CNS)- Efferent (away from CNS)
Fig. 1.12B
This shows a mid-sagittal section
Decussation- crossing of fibers
The biggest is the corpus callosum
Fig. 1.11A (brain with directions drawn in)
Rostral (toward the front)- Caudal (toward the back)
Superior (above) Inferior (below)
(not shown) Lateral - Medial
Fig. 1.11B (brain with sections drawn in)
Coronal (would be cross section if human brain were anterior)
Horizontal vs Sagittal - (would be like longitudinal sections)
Some more recent historical figures and issues
Fig. B2 (blood supply of brain)
Thomas Willis (1621-1675) (English) circle of Willis
fed by both internal carotids, a block would not deprive half of brain of
blood supply
Here is
the equivalent picture from our sheep brain dissection
Fig. 26.1 Pierre-Paul Broca (1824-1880) (France) brain surgery
patient with damage in left hemisphere shows speech loss => lateral localization
vs. Lashley (cortical lesions in learning experiments) mass action
and equipotentiality
In the old days, stroke (defects while living and damage in post-mortem)
was the way to make conclusions in humans; now there are imaging techniques.
In animal models, stereotactic lesions can be made.
Electrical stimulation can also be applied, and, in general, it has the
opposite effect of lesioning.
Fig. 26.2 (Brodmann areas drawn onto human brain)
Korbinian Brodmann (early 20th century) has lots of brain areas with numbers
famous ones: 17-vision, 4-motor, based on cellular cytoarchitecture
Stroke
Current affairs Jan 5, 2006, Israel's premier Ariel Sharon has a stroke
complicated by being on blood thinners.
Box A, Appendix B
Brain's need of oxygen makes interruption in blood flow dangerous
3rd leading cause of death in US
(1) thrombus (local occlusion) 50%
(2) embolus (object in blood stream) 30%
(such interruption in blood supply is called "ischemia")
(3) hemorrhage (e.g. from aneurism) 20 %
Tissue plasminogen activator (TPA) to dissolve clot
Recent reading: CM DeLude "Widening the window" (news scan,
medicine) pp 21-22 Scientific American August 2005
Few get TPA because they come in too late for it to be effective (<3
hr)
If neurons are not dead, TPA may still work; newer CT and MRI scans can
now show this.
Giving oxygen also buys time.
New drug: Desmoteplase (from vampire saliva) like TPA (breaks fibrin) but
more potent and selective.
Structure of the Nerve cell
Fig. 1.2F - (Purkinje cell)
1836 Jan Purkinje (Czech) - Purkinje cells in cerebellum - these are highlighted
with Golgi (see below) staining
Fig. 1.7 (diagram of knee jerk reflex) [again]
1865 Otto Deiters (Bonn) - motor neuron
Fig. 1.3A (cells and connections in brain)
axis cylinder -> axon, dendrites (branches)
reticular theory (connected like blood stream) vs. cell theory (cells
are separate)
1885 Camillo Golgi (Italy) - potassium dichromate fix silver impregnation,
still believed reticular theory
1888-> Santiago Ramon y Cajal - real thorough descriptions of many systems,
believed in cell theory
1906 Nobel
Prize in Physiology and Medicine for "the structure of the nervous
system"
Advancements in cell anatomy methodology
Figs 1.3, 1.4, 1.5 & 1.6 are amazing preview of many semester topics
Beyond the level discussed above, tracts could be found by dissection. Looking
ahead to the sheep brain dissection, this tract dissection of the midsagittal
cut reveals the fornix, the mammilo-thalamic tract and the habenulo-peduncular
tract. See slide
11
Fluorescence. Excitation with short wavelength. While electron is in excited
state, there is some radionless de-excitation. When electron comes to ground
state, it has less energy, so photon emitted has less energy (longer wavelength).
Here is a fluorescence
microscope.
Short wavelength comes (through color filters) from above, hence "epi-illumination"
or "incident illuminator."
Of course, there is a camera.
Fig. 6.11 In the 1960s there was a lot of excitement about how specialized
techniques (histochemical fluorescence) allowed researchers to trace the
pathways used by a specific neurotransmitter substance. Fig. 6.11 shows
dopamine pathways from the substantia nigra to the striatum and the cerebral
cortex.
Fig. 1.6 A-D Nissl stain shows cells (like cell layers in cortex)
Fig. 1.6 E,F Golgi technique only colors a few cells so they can be viewed
in their entirety.
Fig. 1.6 G,H a fluorescent dye can be injected.
Here is a figure
I prepared to explain how antibodies could be used in the electron microscope
to localize proteins. The protein is an antigen. An antibody, binds to an
epitope on the protein. A secondary antibody with an electron dense attachment
(colloidal gold for electron microscopy or a fluorescent label for fluorescence
microscopy) binds the antibody. Here
is a figure I found subsequently) in this
very useful site.
Here is a micrograph
where Rh1, the rhodopsin of one type of photoreceptor in the Drosophila
compound eye, is labeled ("decorated") with immunogold (Sapp et
al, J. Neurocytol. 20, 597-608, 1991)
Here is a laser scanning
confocal microscope, a fancy fluorescence microscope.
This machine is from a grant obtained by Prof.
Spencer (and a few others of us).
For a light source, a laser is used.
Light is measured and fed to a computer for image acquisition.
Low depth of field (only one plane is in focus) provides "optical sectioning"
Images are very clear.
Here is Rh1
labeled with a fluorescent antibody in the confocal
Fig. 1.4 A Tau (red) (microtubular binding protein in axons) accumulates
in Alzheimer's, tubulin (green) in cells
Fig. 1.4 B Developing cell in culture has actin in growing tips.
Confocal
I will give you a demonstration of some unique imaging using confocal microscopy.
Review utilizing Sylvius
A CD came with your book and we will use it for various views of :
Broca's area, Wernicke's area, motor cortex, auditory cortex
Brodman's areas, famously 4 (precentral gyrus=motor cortex), 17 (visual
cortex)
Occipital lobe
Postcentral gyrus
Spinal cord (including cervical and lumbar enlargements of gray matter for
fore- and hind-limbs
Striatum
Substantia nigra
Brain imaging techniques
(Box A - three figures) MRI
Alumnus research in neuroscience
Adrian A. Epstein, SLU class of 2002, took this course from me in 2002 (and
introductory biology earlier). After that, he went to Washington University
and is a research assistant in biological imaging (in the Department of
Radiological Sciences). He is first author of several abstracts (convention
presentations) and is coauthor of J. S. Shimony et al., Diffusion tensor
imaging reveals white matter reorganization in early blind humans, Cerebral
Cortex, 2006. Here, they use a specialized technique called diffusion tensor
imaging to trace tracts (hence DTT= diffusion tensor tractography) to compare
the visual projection in normal and blind subjects.
Some useful information and links
Neuroscience at SLU is centered in Medical school departments of Center
of Anatomical Science and Education and Department
of Pharmacology-Physiology. Outlines from my signal
course in biology might be helpful sometimes. Dr
Buchanan is the new neuropsychologist. Dr.
Anch in Psychology teaches 4 courses in physiological psychology relevant
to Neuroscience, PSY-A415-01: Science
of Sleep, PSY-A513-01: Advanced
Physiological Psychology, PSY-A413-01: Physiological
Psychology, and PSY-A414-01: Drugs
and Behavior. Dr.
Spaziano's CH-A445 Principles of Medicinal Chemistry is also somewhat
relevant to this topic. There is a philosophy professor, Dr. Terzis, who
teaches a relevant course PL A-482-01 "Biology and Mind" which
is relevant to this topic.
Here are some web sites for your present and future reference:
Society for Neuroscience
Neurosciences on the internet
Exam questions from 2005 - 2007 related to this outline
Without answers
What makes it so that Tau, a microtubule-binding protein, fluoresces red
in the confocal microscope?
What function is localized to Brodmann area 17 in the occipital lobe?
Why was the technique developed by Golgi and utilized by Ramon y Cajal so
useful for studies of cellular architecture?
For the knee jerk reflex, where (be specific) is the cell body of the motor
neuron?
One of the most famous examples of localization of function is Broca's area,
used for what?
Why would tissue plasminogen activator (TPA) be contraindicated in 20% of
stroke victims?
A coronal section of the brain was shown revealing the caudate, putamen
and globus pallidus, involved in coordinating motor movements. These structures
are collectively referred to as what?
Why is the optic "nerve" (the second cranial "nerve")
actually a tract?
What information (and in what direction) is carried by axons of the cells
in the dorsal root ganglion?
Why might half of your brain be saved it there were a unilateral occlusion
affecting one internal carotid artery?
What is the huge decussation seen as white matter in a midsagittal section
of the brain?
If Santiago Ramon y Cajal (famous proponent of cell theory) knew what we
knew now, how would he have used the chemical synapse in his arguments against
Camillo Golgi's reticular theory?
What is the function of Brodmann's area #4, the precentral gyrus?
The text figures with several proteins (like tau plus tubulin) labeled different
colors in a nerve cell look really nice! One reason is that out-of-focus
cells do not degrade the image. How did "they" acheive this?
The "nigro-striatal dopamine tract" is implicated in Parkinson's
disease. It goes to the striatum. Where does it come from?
Under what circumstances would you label your antibody with colloidal gold
vs a fluorescent dye?
With answers
What makes it so that Tau, a microtubule-binding protein, fluoresces red
in the confocal microscope?
need to bind antibodies tagged with fluorescent dye
What function is localized to Brodmann area 17 in the occipital lobe?
vision
Why was the technique developed by Golgi and utilized by Ramon y Cajal so
useful for studies of cellular architecture?
by staining very few cells (in their entirety) they could be seen even though
many other cells were nearby
For the knee jerk reflex, where (be specific) is the cell body of the motor
neuron?
ventral horn of gray matter in spinal cord
One of the most famous examples of localization of function is Broca's area,
used for what?
language
Why would tissue plasminogen activator (TPA) be contraindicated in 20% of
stroke victims?
do not want to interfere with clotting if there is hemorrhage
A coronal section of the brain was shown revealing the caudate, putamen
and globus pallidus, involved in coordinating motor movements. These structures
are collectively referred to as what?
basal ganglia
Why is the optic "nerve" (the second cranial "nerve")
actually a tract?
eye and this "nerve" are part of the CNS
What information (and in what direction) is carried by axons of the cells
in the dorsal root ganglion?
somatosensory (also muscle stretch, etc.) afferent
Why might half of your brain be saved it there were a unilateral occlusion
affecting one internal carotid artery?
because the circle of Willis would bring blood from the other side
What is the huge decussation seen as white matter in a midsagittal section
of the brain?
corpus callosum
If Santiago Ramon y Cajal (famous proponent of cell theory) knew what we
knew now, how would he have used the chemical synapse in his arguments against
Camillo Golgi's reticular theory?
Cells, being separate, must communicate
What is the function of Brodmann's area #4, the precentral gyrus?
Motor cortex
The text figures with several proteins (like tau plus tubulin) labeled different
colors in a nerve cell look really nice! One reason is that out-of-focus
cells do not degrade the image. How did "they" acheive this?
Confocal microscope (optical sectioning, low depth of field)
The "nigro-striatal dopamine tract" is implicated in Parkinson's
disease. It goes to the striatum. Where does it come from?
substantia nigra
Under what circumstances would you label your antibody with colloidal gold
vs a fluorescent dye?
coloidal gold for electron microscopy, fluorescent dye for standard and
confocal fluorescence microscopes
What is the function of the choroid plexus situated in the ventricles?
secrete cerebro spinal fluid (CSF)
Why are the "basal ganglia" called "basal nuclei" in
some treatments (like the transparency from the introductory book that I
showed)?
cells and connections in the CNS are called nuclei
What substance is missing in gray matter (but is present in white matter
and makes white matter white)?
myelin
What colossal body is seen in mid-sagittal section that connects left and
right hemispheres?
corpus callosum
What is the anatomical name of the combined medulla, pons and midbrain?
brain stem
For which kinds of stroke might you use desmoteplase (from vampire saliva)?
those caused by thrombus or embolism
How could all the details of the dendritic tree of a cerebellar Purkinje
cell be revealed when that cell is in the neighborhood of "zillions"
of other cells?
Golgi staining technique only highlights one cell out of how many
What optical phenomenon, important in microscopy, was demonstrated when
I shined an untraviolet (UV) light (that you could not see) onto my shoe
laces and they shined a bright blue?
fluorescence
Suppose I'm interested in the subcellular localization of a protein (such
as tau, actin, tubulin or rhodopsin). Why do I need two antibodies to visualize
the protein?
one to bind the protein of interest, the secondary directed against the
first with fluorescent or electron dense label
Scientists in Brocca's time needed to wait until autopsy to find the localization
of function damaged by stroke (or tumor or whatever). What allows us to
see into the brain of a subject or patient nowadays?
imaging (CT, PET, MRI)
Low depth of field and optical sectioning allow unique computer-generated
views in which a stack of optical sections can be rotated. What technique
is this?
Confocal microscopy
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