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5 historical stages of neuroscience
1. egyptians + Greek: heart or brain as seat of conciousness? egyptians= heart and greek = brain 5000 years ago/ 1600 BCE
2. romans up to renaissance/ enlightenment: ventricular fluid mechanical model, 200 CE
3. victorian era (1800)s to modern day: nerves as wires
4. 1800s up to modern day lozalization
5. 20th century to modern day: mechanisms- cellular, molecular, and systems
PNS and CNS relationship
sensory ganglia in PNS bring in info about environment to the CNS, info is processed here, and motor CNS neurons recieve a decision and send signals to muscles via PNS
glia
"support" cells to neurons, but have very important circuit functions. 4 types of cells (astrocytes, ogliodendrocytes, microglia, ependymal)
astrocytes
controls chemical content of the neuronal extracellular space, most numerous glial cell
ogliodendrocytes
CNS myelin sheath that wraps neuronal axons, affects transmission
microglia
brain inflammatory cell, synaptic pruning
ependymal cells
line the brain ventricles and control cerebrospinal fluid homeostasis
other cells: endothelial and pericytes
endothelial: brain blood vessel cells, arteries, veins and capillaries
pericytes: regulate capillary function, contribute to BBB by interactions with endothelial cells
Golgi v Cajal
golgi believed all neurons are connected like vessels in the circulatory system. cajal believed they were unfused and distinct cells, and he won the debate
Nissl Stain
Nissl stains rough ER. this helps us see the cell bodies. . You can stain both this and golgi at the same time too
golgi stain
Golgi stains random intermediate cells. Golgi only stains some neurons for some reason which is great because then we can better see the structure of neurons. stain reveals entire neuron, dendrites, soma and axon.
soma
cell body, 20 um in diameter. contains the nucleus, which is surrounded by a nuclear membrane. has organelles
mitochondria
widespread thru out cytoplasm of soma, and in presynaptic axon and post synaptic dendrite regions.
mitochondria functions
1. ATP production (brain consumses most of bodies ATP, and has more mitochondria than other cell types)
2. neurotransmitter release
3. apoptosis
4. neurite/ dendrite outgrowth
alcmaeon of croton
first greek to believe the brain was the seat of thought, described the optic nerve and all senses except for touch
hippocrates
father of medicine, four elements (earth air fire water) are linked with 4 bodily fluids called humors. Described paralysis and seizures
aristotle
believed the heart was the center of intellligence, and the brain is for cooling blood
herophilus
dissected humans to differentiate arteries and veins, father of anatomy, observed sensory and motor nerves, brain is the seat of intellect, described brain ventricles in detail
Galen
thought sensations and memories were formed in the cerebrum because it felt soft, and muscles were controlled by cerebellum because it felt hard. he also created an early version of the ventricular fluid model based on flow of anima, spirits. he identified 7 of the 12 cranial nerves
vesalius
accpeted the ventricular theory but applied a more mechanical aspect. he also named the pons and hippocampus
monkeys
great vision, similar brain circuits as humans, not great for classical genetics
mice
great for genetics, strong somatosensory system, strong olfaction, but poor vision
3 R's of animal use in research
replacement, reduction, refinement
soma size
20 micrometers (micron)
what is the most numerous neuron in the whole brain
cerebellar granule cells
cytoplasm
gel like material, also a buffer to prevent pH swings
chromatin
consists of double stranded DNA and histones that pack the DNA into a small space
phosphate group on dna
gives it a negative charge
genes that make structural RNAs but not proteins
ribosomal RNA and tRNA
transcription
DNA is transcribed to make mRNA in the nucleus
translation
mRNA is translated to make protein in the cytoplasm (the ribosome is the machine that does this)
RNA polymerase
binds to promoter (a specific sequence) and pries the 2 strands of DNA apart. one of them will serve as the template strand. it will then more down and synthesize mRNA
mRNA
pre- mRNA is spliced (introns are cut out). leaves the nucleus thru pores and enters the cytoplasm where it will find a free ribosome
heterochromatin
inactivated chromatin due to genes being tightly wrapped around histones. dna wrapped tightly around it cannot be acessed by transcriptional machinery
euchochromatin
genes that have been unwound from the histones, and are now active chromatin
how epigenetics work
it alters the way DNA wraps around histones
epigenetic marks
change the 3D structure of DNA but not the sequence thru winding or unwinding
DNA methylation
addition of a methyl group to DNA, which inactivates expression of the gene
tRNA
serves as a link (or adaptor) between the messenger RNA (mRNA) molecule and the growing chain of amino acids that make up a protein
tRNA anti-codon
ribosome
machine that attaches to the mRNA and makes a protein. reads the mRNA sequence and pairs the codon with a specific tRNA anti-codon
smooth ER
synthesis of lipids for making new cell membrane
rough ER
has ribosomes for making proteins, it is continous with the outer nuclear membrane this is what is revealed in the Nissl stain
golgi apparatus
modifies, packages, and transports stuff. post-translational processing of proteins (adding carbohydrates and lipids) and traffics membrane proteins to different parts of the cell such as axons and dendrites
where are the RER and golgi app on the neuron
they extend into dendrites, but not axon
axon hillock
portion adjacent to the cell body that generates the AP and also serves as a filter to select materials to traffic from the soma to the axon
axon collaterals
axon branches that split or bifurcate off of the main axon
axon varicosities
swellings that release NTs along the length of an axon
axon terminals
small enlargements at the end of the axon that store and release neurochemicals; the presynaptic element
parallel fiber
single axon from granule cells which bifurcate into two brances that form many other contacts with purkinje cell dendrites (looks like powerlines)
climbing fiber
the axon from inferior olive neurons (in the brain stem) and makes two contacts in the cerebellum. it contacts the deep cerebellar nuclei neurons using a single terminal bouton, but the main axon climbs like a vine making many contacts on Purkinje cell dendrites
ribosomes and axons
there are few ribosomes here, controversial because there are some RNAs there. so at least some protein synthesis occurs there.
why is there need for trafficking molecules down the axon
axon does not have rough ER or golgi
dendrites
recieve info from other neurons, spine number and shape is always changing based on activity of their inputs, involved in synaptic plasticity associated with learning and memory
cell biology of dendrites
-there are lots of ribosomes here especially beneath synaptic spines, and very many mRNAs are trafficked into the dendrites
-rough ER and golgi extends into the dendrites
-lots of ribosomes in the base of the dendritic spines
are proteins synthesized in the dendrites
some are, but some are made in the soma and trafficked here
evidence that neuronal function depends on trafficking (wallerian degeneration)
when an axon is cut, it dies distal to the injury
retrograde regeneration
loss of axon and or neuron proximal (on the soma side) to injury
role of cytoskeleton
controls shape, trafficking/ movement of organelles and molecules into dendrites and axons. there are three main components
microtubules
-serve as tracks for LONG RANGE movement of mitochondria and other cargos up and down axon and dendrites
-made of tubulin (protein)
actin microfilaments
-control cell shape, spine and presynaptic terminal shape + plasticity, and form tracks for LOCAL movement into pre and post synatpic elements
-covers entire surface of the neuron underneath the membrane
-often seen at synaptic terminals and dendritic spines, helps their growth and movement
-unique ring structure
-made of F-actin polymers
neurofilaments
-control diameter
-work with the microfilaments to control shape
-do NOT serve as tracks and instead are transported down microtubules
-help with signal propogation by controlling axon caliber so if someone lacked these in a mutation they'd have slower AP
axoplasmyic transport
moves proteins from soma to axon but also delivers cargo to dendrites. net movement is anterograde but it occurs in both directions
anterograde transport
newly made proteins are packaged in the soma and transported down toward axon terminal (motor: kinesin)
retrograde transport
waste material & signaling molecules are carried from the terminal to soma for recycling (motor: dyenin)
autophagosomes and endosomes
vesicle-like recycling structures
slow axoplasmic transport
mainly for cytosolic proteins like neurofilaments
fast axoplasmic transport
used for synaptic vesicles, membranous organelles and proteins
track and motor switching
in dendritic spines and axon terminals, cargoes can be switched from an anterograde kinesin motor to a myosin motor
contrast the three types of motors
anterograde kinesin, dynein for retrograde, both are for LONG RANGE traffic and use microtubules as tracks. myosin is for SHORT RANGE and SWITCH to microfilaments as tracks
triparte synapse
presynaptic element (axon), post synaptic element (dendrite spines), and astrocyte that wraps around them that's role is to re-uptake NT from the cleft
neuroligins
postsynaptic cell adhesion proteins that interact with presynatpic neuroexins. this is the "glue" for the synapse
Shank and PSD-95
postsynaptic proteins that are part of the synapse glue. mutations in them may contribute to austism
4 classification of neurons
number of neurites, shape of dendritic tree, connectivity, and chemistry
1. number of neurites
-Unipolar: soma, one horizontal branch extends from it. one part is axon, the other is dendrite. this is sensory ganglia cells
-bipolar: two structures extend from soma (in retina and olfactory bulb)
-multipolar: normal looking, how most neurons are. one axon, many dendrites (dendritic tree)
2. shape of dendritic tree
-pryimidal cells (all spiny)
stellate cells (some spiny, some aspinous)
3. connectivity
A. sensory neurons: gather info from sensory receptors and carry it to the brain
B. interneurons: small neurons that connect other neurons to each other (CNS)
C. motor neurons: receive info from the brain and carry signals to the muscles
4. chemistry
A. NT's and enzymes that make them
B. gene expression
astrocytes and their function
transport water, modify signaling at synapse, release gliotransmitters, end feet wrap around vessles and contribute to BBB, become reactive after CNS injury, sequester excess K+, support neuron growth, recycle GABA and glutumate
they can divide and are the source of most brain tumors
microglia and their function
native resident immune cell of CNS (as opposed to microphage), self-renewing, scan surroundings, motile, ingest debris and dying cells, can be activated or inactivated by environmental stressors, involved in synaptic pruning during development (major contributer in Alzhemiers)
ogliodendrocyte
CNS, myelinate axons, each can myelinate internodal segments of 30-60 axons, can be regenerated if damaged
nodes of ranvier
gaps in the myelin sheath
schwann cells
PNS, myelinate one axon, involved in peripheral axon regeneration