Download - Ch23 Neuron Migration Stem Cells
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Development
Neuron migration
Neurotrophins
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Neurobiology BIO 475
Birth order and cell fate: cortex
!ase study: mammalian cerebral cortex
" cortex is layered structure
" distinct neuron types in each layer
" layers are formed se#uentially
Inside early$ outside late
li%e rings in a tree trun%
" different types of neurons are added in aprecise se#uence
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Neurobiology BIO 475
&ayers in cerebral cortex
'everal layers I: incoming axons
II$ III: pyramidal cell
layers
" pro(ect to neighboringcortex
I): stellate cells
" local pro(ections
)$)I: pyramidal cells " *ro(ect out of cortex
+ig ,-.
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!ortical layers develop Neurons populate in an inside/out se#uence-
&ater born neurons must migrate past earlierborn-
&ayer identity is a function of both neuron andenvironment-
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Neurobiology BIO 475
!ortical layers: inside/out order Determining birth dates of neurons: pulse/label strategy
" in(ect radioactive thymidine in short pulse
" only cells in '/phase 0ill incorporate into DN1
" cells that soon terminally divide are heavily labeled
" cells that continue to cycle 0ill dilute label
" pulse label at various times during development$ collect and section brain after birth
" In 0hich layer do labeled cells end up2
3esult in mon%ey: " early born deep
" late born superficial
'anes$ Development ofthe Nervous 'ystem
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Neurobiology BIO 475
Neurons reach their layer by climbing radial glia
ethod for both cortex andcerebellum-
Neurons and glia interact toguide neuron migration
3eeler mouse has migrationdefect-
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Neurobiology BIO 475
6uman cortical migration
defects Defects in cortical migration are fairly common
" heterotopias:
!lumps of neurons caused by regional defects in corticallayering
" 859 of childhood epilepsy patients have heterotopias &arge enough to be visible in 3I brain scans
!lumps of neurons form abnormal connections$ 0hich maycause epileptic firing patterns
&issencephalydouble cortex syndromes
" massive defects in cortical neuron migration " ;smooth brain< phenotype$ 0ith thic%er cortex$ or less severe
resulting from extra layers of cells ;hung up<
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Neurobiology BIO 475
=ato and Dobyns$ 6uman olecular >enetics$ 8??@$ )ol- A8$ 3evie0 Issue A R89-R96
Lissencephaly and the molecular basis of neuronal migration
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Neurobiology BIO 475
6uman cortical migration defects
&issencephalydouble cortexsyndromes " massive defects in cortical
neuron migration
" ;Double cortex<
Outside layer present But inner dar% area is
abnormal
" ;smooth brain< phenotype$ 0iththic%er cortex$ or less severeresulting from extra layers of cells
;hung up<
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Neurobiology BIO 475
1dult neural stem cells Ongoing neurogenesis in the brain 0o main locations in brain
" )entricular Cone of cortex igrate to olfactory bulbs " 6ippocampus
*ossible role in memory formation " !oncept: stem cell niche
a special place that promotes stem cells 'timulates stem cell properties$ controls ho0 many divide and ho0
many differentiate
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Neural stem cells 'tem cell definition
" 1dult neurogenesis: discovery " *roliferation slo0E$ potential$ niche " &ocations in human brain
'ignals that regulate neurogenesis " Fxercise$ depresssionstress$ anti/depressants
+unction of ne0 neurons " Need to migrate homingE$ differentiate$ integrate into existing circuits " *hysiologically different: more easily excited$ more inputs " 3e#uired for ne0 memory formation
i*'!s " 3ecipes for inducing stem cells
" 3ecipes for differentiating stem cells " *atient/derived i*'!s: differentiated neurons as disease models
Neural stem cells " *romise: *ar%insons$ 1&' " *roblemslimitations
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8?A8 Nobel *riCe: Induced
pluripotent stem cells
Gohn >urdon$ !ambridge " In A,.?s: nuclear
transplantation " +rog egg: removed nucleus " 3eplaced 0ith a ne0 cell
nucleus " Ne0 nucleus 0as able to drive
development to complete frog
Nucleus retains full potency
'hinya Hamana%a$ =yoto niv " Discovered set of transcription
factors expressed by stem cells " ransfected them into fibroblastss%in cellsE
" urned them into stem cells
ature cells reprogrammed tobe pluripotent: " able to differentiate into any cell
type
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>rades may not be good
predictors of success
John Gurdon’s biology report
card, Eton College, 1949
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Neurobiology BIOL 475
6ippocampus: center for adult
neurogenesis
ain region of adult neurogenesis
!ontains neural progenitors
In rodents$ about ,$??? ne0 neurons bornper day
!ould this be associated 0ith memory
function of hippocampus2
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Neurobiology BIOL 475
Ne0 neurons re#uired for
memory *revent neurogenesis$ prevent ne0 spatial
memory
Fxperiment in young adult mice
!lue that adult neurogenesis may have
functional role in long term memory
1- Irradiate to %illadult neural
progenitors stem
cellsE
B- A 0ee%:able to learn
maCe
!- est at 8$@$4 0ee%s- +ailedto remember location of
platformJ disrupted long term
memory
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Khat is neuroscience2
'tudy of the nervoussystem
" *hysics$ chemistry
" >enetics$ molecularbiology " cell biology$ developmental
biology " physiology$ anatomy$
endocrinology " psychology$ behavior$
neurology " 1nimal behavior$ evolution
'lide A. BIO& 475.75 Neurobiology
Diffusion tensor 3I of human brain
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- eurons:functional units
of the nervoussystem
Ke 0ill learn:
ni#ue cell biologyof neurons
6o0 neurons
transmit electrical
signals
6o0 neurons signal
to each other
'lide A7 BIO& 475.75 Neurobiology
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'ystems: net0or%s of neurons
control sensory perception Input: sensory
systems
" 'ense external
stimulus transduction *hoton$ chemical$
sound 0ave$ touch
" !hange into signals
0ithin net0or%s
" !reate an internal
representation of
outside 0orld
'lide AL BIO& 475.75 Neurobiology
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M and control movement otor system:
" !ontrols muscle contractions " 3eflexes$ coordinated movements
'lide A, BIO& 475.75 Neurobiology
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ental illness and neurological
diseases Devastating diseases
" Often life/long
" Impacts across society
'ome gain uni#ue abilities
!an 0e understand their
causes2
" >enes$ molecules$ neurons
!an biology help to
discover treatments2
'lide 8? BIO& 475.75 Neurobiology
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6o0 does the brain build itself2 Development of the brain in the
embryo
" Khat defines the nervous system2
" 6o0 are neurons born2
" 6o0 do neurons connect2 he dynamic brain: learning and
memory
" he brain changes its o0n
structure " Ne0 neurons are born
" !onnections are made and lost
'lide 8A BIO& 475.75 Neurobiology
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Our Neurobiology semester
Neurons
1ction potentials
'ynapses
Fxam A 'ept 85
'ection A
'lide 88 BIO& 475.75 Neurobiology
'ection 8 'ection @
'ensory systems
!hemical$ visual$auditory$ somatic
otor systems
Fxam 8 Oct @?
ental illness
&earning andmemory
Neural development
+inal Dec AL