EMBRYOGENESIS SYSTEM NEUROSCIENCE: NERVOUS SYSTEM RETINA
neurulation !!! DEVELOPMENT = invagination of neural tube
= production neural tube, B-vesicles & spinal other factors involved in neural induction:
cord > neuronal plate: NT3
> surface ectoderm
a) dotted line = production notochord > LPM: BMPs
(mesoderm)
→ sends out TF (Shh & Noggin) to
> PM: Twists PATTERNING
> endoderm = molecular & cellular specification area’s
ectoderm
b) ectoderm is going to raise converted to 5 B-vesicles: of developing tissue
c) development butterfly shape > pro divides in 2:
→ from this moment 2 ≠ ectoderms: • telencephalon = cerebral cortex SONIC
> white = surface ectoderm • diencephalon = thalamus, hypothalamus, HEDGEHOG
> blue = neurectoderm (lays pineal gland & retina PROTEIN
elevated on suf. ectoderm) > mesencephalon = midB
> rhom divides in 2: = ventralizing factor prod. by notochord
d) central<<< part butterfly penetrates
• metencephalon → prod. in ventral region: induces
into depth
• myelencephalon floorplate & ventral cell types in
→ formation neuronal pit/groeve
1. surface ectoderm / 2. neuronal plate / neural tube
3. neuronal pit / 4. neuronal crest with cells / DEVELOPMENT VENTRICULAR
5. neuronal tube / 6. spinal ganglion / 7. neuro- SYSTEM
porus cranialis/anterior / 7. neuroporus caudalis/ BMP4
posterior / 9. notochord / 10. primitive knot / = bone morphogenetic protein 4
11. primitive line / 12. somites = dorsalzing factor prod. by notochord
e) indentation (instulpen) neuroectoderm: (sextra info embryology for primitive line etc.) → prod. in dorsal region: induces
2 sides of the pit grow to each other roofplate & commissural intern
& melt together (see as jacket with neuronal tube rise to entire NS & all circuits !!! + shedding part of dorsal cells
2 zippers: begins in the middle & 1 --> move away from tube
zipper closes caudal & other cranial) neuronal tube defects: --> form crest cells: forms
f) creation neuronal tube: completely > anencephaly = error at cranial neuroporus many ≠ cells & tissues
separated from surf. ectoderm → no B bcs of no closure neuronal tube → works together with Sonic P:
(is laying under it) > spina bifida = error caudal neuroporus make a dorsal-ventral axis !!! for
g) between surf. ectoderm & later differentiation
neuroectoderm neuronal crest cells
B-DEVELOPMENT
= special migrating cells neuronal tube forms 3 dilatations pigments cells, cartilage, connective
h) cranial & caudal parts stay open = B vesicles: tissue, N, glia cells,...
temperately > prosencephalon = foreB
= neuroporus cranialis & caudalis > mesencephalon = midB
→ needs to close: o/w neuronal → stays like it is
tube defects > rhombencephalon = hindB
, TbR2 = TF in subventricular zone also tangential migration ~ Tarzan: jump
RHOMBOMERES DEVELOPMENT CEREBRAL from 1 location to another → not
→ radial glia’s -> intermediate progenitors
= regional ≠ in rostro-caudal axis bcs of CORTEX marker completely understand
swelling of the neuronal tube cortex -> ≠ layers → no TbR2?: → eg. intern migration in cortex from
→ only visible at 29day embryo -> less N = B smaller: cortex smaller ventral foreB
→ each rhombomere ≠ size & shape !!! layer = ventricular zone (VZ): contains -> developmental delays
+ express specific Hox genes in N & glia progenitors -> expands massively -> agenesis corpus callosum MECHANISMS THAT
specific combinations (above VZ subventricular zone) CONTROL MIGRATION
→ specific combination will result → first prod. N from preplate (PP) environmental factors also influence on B!!:
> contact-mediated attraction:
in segmental arrangement → their axons + thalamus axons form eg. fetal alcohol syndrome
connection new N~radial glia cell
cranial nerves intermediate zone (IZ) eg. Zika virus: targets progenitor cells
stimulates gap junction formation
→ after this generation N cortical → microencephaly
→ !!! for maturation
Hox genes regulated by morphogens layers II-VI: form cortical layer > contact-mediated inhibition
= signaling factors: directs cell fate & NEURODEVELOPMENTAL
> chemoattraction
tissue development at a distance from split perplate in: DISORDERS > chemorepulsion
their source > marginal zone = future layer I > spina bifida
→ they induce pattern formation > subplate > anencephaly = underdeveloped B MIGRATION DEFECTS
→ response to morphogen altered by > congenital syphilis & toxoplasma
previous patterning tissue these layers form the 6 layers of cortex > schizophrenia not very !!!, but know that it’s possible
> autism → change in cortex factors?
conserved in many spp. > epilepsy -> migration defects
→ same role & orientation in humans & fruit
flies + very homologue APOPTOSIS DIFFERENTIATION
large part of N during development will be in B >100 ≠ N → how so many?
PROLIFERATION apoptosed > genetically programmed fate choices
→ high regulated + key process in develop- > TF in ≠ stages of development
CNS DEVELOPMENT ment (or combo’s of TF)
see B-development RADIAL GLIA > temporal & spatial segregation
long unknown which cell type produced N caspase 9!!! > environmental factors
NEUROGENESIS IN VZ & SVZ → know now it are radial glia cells: → no caspase = bigger B & more B-defects > conserved genetic programming for
located in ventral part & come from neurogenesis
in lining hollow neuronal tube proliferating
cells neuro epithelium cells
MIGRATION > combinatorial transcription code
= neuronal epithelium cells -> divide → divide in 12-24h in other cells: all radial glia cells = substrates for migration (eg. TbR2)
cells neuro epithelium related → produced N keeps hanging on glia cell for → all specify which N it will become
!!! proliferating marker a while
= phospho histone H3 → uses glia as guide to migrate to HUMAN ORGANOIDS
→ ventral part higher proliferation, but final destination = induced pluripotent cells
most of cortex born in dorsal part = radial migration: nicely oriented → used to model human B-disorders
-> 80% N = glutamatergic N & start from ventricular zone & early stages B-development
-> 20% GABAergic N: regulate → eg. cerebral cortex: inside out
excitatory N formed --> 6->5->4->3->2->1
, NEURONAL POLARITY
N reaches final destination
→ start further differentiation: formation
neuronal polarity with input (dendrite)
& output (axons) zones
→ development axonal growth cone
= extension of developing N looking for
synaptic target
→ highly motile, determines growth
direction & interact with ≠ cells
REFINING CONNECTIONS
initial connections not always good: eg. in-
correct target nucleus
→ need regulation
→ neuronal death, axonal retraction
& synapse elimination
SURVIVAL PRESYNAPTIC
CELL
survival regulated by:
> trophic factors prod. by their targets
= neurotrophines: nerve growth factor,
B derived neurotrophic factor &
neurotrophin 3
• secreted P
• NGF !!!!! for survival in development
• all factors promote N extension,
axonal regeneration & synapse
formation
• act via specific R: TRKs
SYNAPSE FORMATION
axonal filaments when connected
properly change in shape
→ forms: presynaptic element,
cleft (15-30nm) & postsynaptic
elements (with R for NT)
, PAVLOVIAN CONDITIONING THE PLASTIC BRAIN
2 !!! concepts for plasticity:
I. MEMORY SIMPLE LEARNED BEHAVIOR IN MEMORY DEFECT AFTER
II. LEARNING = acquisition knowledge/skills APLASIA
through study, experience or being taught HIPPOCAMPAL DAMAGE
→ 1st scientist that looked at learning Eric Kandel: used sea slug to study learning Henri M.: patient with recurrent epileptic
processes in aplasia seizures
& how behavior changes when you learn
A-B) touch siphon -> redraws gill (yellow) → consulted neurologist Scoville: cut piece
= Pavlov
= preventive mechanism temporal lobe away
→ repeat: slug habituates → helped Henri, but Scoville didn’t know
classical conditioning !!!!: dog -> show dog food
-> saliva production -> proceed presentation → now painful stimuli to siphon: function temporal lobe (hippocampus!!)
food with bell -> after while just bell will faster response (dark blue) DISCOVERY SYNAPTIC
induce salivation (light blue = learning period necessary to store new info PLASTICITY IN HIPPO-
→ after learning period bell induces salivation for touch siphon) → Henri couldn’t learn anything CAMPUS CONFIRMS
= Pavlovian conditioning after operation (even family)
HEBBIAN THEORY
HEBBIAN PLASTICITY & LEARNING & MEMORY IN study: isolated hippocampus & made
CONDITIONING ANIMALS sections
90% work biomedical science done in rats & → put stimulation electrode on Schaffer
psychologist Hebb: though synapse collaterals hippocampus &
connections change as result of experience mice
registration electrode CA1 region
→ 2 cells connected via synapse C) neuronal network of aplasia gill-withdrawal → to look at learning Hampton court maze → start stimulation:
→ use of synapse = synapse efficiency↑ reflex: used = labyrinth
→ nowadays not used anymore: now > low freq. stimulation: gives
→ re-suse synapse: changes efficiency > MN = motor N = withdraws gill same response
& builds information > SN = sensory N = register touch gill Morris water maze
> high freq. stimulation: N goes
> 5HT N= serotonine N = register electric back to initial situation, but
classical conditioning according to Hebb: shock → modulates blue connection MORRIS WATER MAZE
after h the response is
US = unconditioned stimulus = food of SN -> MN B) time needed to reach platform intensified = potentiation
CS = conditioned stimulus → see learning curve: after #days
→ learning process results in change in training animals reach platform faster shows that hippocampus has
connections between cells that register C) memory training Hebbian synapse !!!
ringing bell & N that elicit response → remove platform & see in which
(salivation) quadrant animal was most = synapses that get better when used
→ in end ringing bell = salivation → most time in quadrant where (here high freq. stim. potentiates
→ learning = new connections OR platform was originally ↑ synapses-efficiency)
enhancing existing connections D) shows that learning = based on synapses
→ argument that animal was
→ intervention 5HT N modifies connection synapses -> glutamate R: NMDA & AMPA
really learning !!!
SN & MN → NMDA !!! role in potentiation
D) strategies to find platform:
→ learning process situated at level → why NMDA? -> distributed highly
> spatial: uses higher part of B
modulation synapses in cerebral cortex, hippocampus &
> systematic
> repetitive: no use higher parts B striatum
neurulation !!! DEVELOPMENT = invagination of neural tube
= production neural tube, B-vesicles & spinal other factors involved in neural induction:
cord > neuronal plate: NT3
> surface ectoderm
a) dotted line = production notochord > LPM: BMPs
(mesoderm)
→ sends out TF (Shh & Noggin) to
> PM: Twists PATTERNING
> endoderm = molecular & cellular specification area’s
ectoderm
b) ectoderm is going to raise converted to 5 B-vesicles: of developing tissue
c) development butterfly shape > pro divides in 2:
→ from this moment 2 ≠ ectoderms: • telencephalon = cerebral cortex SONIC
> white = surface ectoderm • diencephalon = thalamus, hypothalamus, HEDGEHOG
> blue = neurectoderm (lays pineal gland & retina PROTEIN
elevated on suf. ectoderm) > mesencephalon = midB
> rhom divides in 2: = ventralizing factor prod. by notochord
d) central<<< part butterfly penetrates
• metencephalon → prod. in ventral region: induces
into depth
• myelencephalon floorplate & ventral cell types in
→ formation neuronal pit/groeve
1. surface ectoderm / 2. neuronal plate / neural tube
3. neuronal pit / 4. neuronal crest with cells / DEVELOPMENT VENTRICULAR
5. neuronal tube / 6. spinal ganglion / 7. neuro- SYSTEM
porus cranialis/anterior / 7. neuroporus caudalis/ BMP4
posterior / 9. notochord / 10. primitive knot / = bone morphogenetic protein 4
11. primitive line / 12. somites = dorsalzing factor prod. by notochord
e) indentation (instulpen) neuroectoderm: (sextra info embryology for primitive line etc.) → prod. in dorsal region: induces
2 sides of the pit grow to each other roofplate & commissural intern
& melt together (see as jacket with neuronal tube rise to entire NS & all circuits !!! + shedding part of dorsal cells
2 zippers: begins in the middle & 1 --> move away from tube
zipper closes caudal & other cranial) neuronal tube defects: --> form crest cells: forms
f) creation neuronal tube: completely > anencephaly = error at cranial neuroporus many ≠ cells & tissues
separated from surf. ectoderm → no B bcs of no closure neuronal tube → works together with Sonic P:
(is laying under it) > spina bifida = error caudal neuroporus make a dorsal-ventral axis !!! for
g) between surf. ectoderm & later differentiation
neuroectoderm neuronal crest cells
B-DEVELOPMENT
= special migrating cells neuronal tube forms 3 dilatations pigments cells, cartilage, connective
h) cranial & caudal parts stay open = B vesicles: tissue, N, glia cells,...
temperately > prosencephalon = foreB
= neuroporus cranialis & caudalis > mesencephalon = midB
→ needs to close: o/w neuronal → stays like it is
tube defects > rhombencephalon = hindB
, TbR2 = TF in subventricular zone also tangential migration ~ Tarzan: jump
RHOMBOMERES DEVELOPMENT CEREBRAL from 1 location to another → not
→ radial glia’s -> intermediate progenitors
= regional ≠ in rostro-caudal axis bcs of CORTEX marker completely understand
swelling of the neuronal tube cortex -> ≠ layers → no TbR2?: → eg. intern migration in cortex from
→ only visible at 29day embryo -> less N = B smaller: cortex smaller ventral foreB
→ each rhombomere ≠ size & shape !!! layer = ventricular zone (VZ): contains -> developmental delays
+ express specific Hox genes in N & glia progenitors -> expands massively -> agenesis corpus callosum MECHANISMS THAT
specific combinations (above VZ subventricular zone) CONTROL MIGRATION
→ specific combination will result → first prod. N from preplate (PP) environmental factors also influence on B!!:
> contact-mediated attraction:
in segmental arrangement → their axons + thalamus axons form eg. fetal alcohol syndrome
connection new N~radial glia cell
cranial nerves intermediate zone (IZ) eg. Zika virus: targets progenitor cells
stimulates gap junction formation
→ after this generation N cortical → microencephaly
→ !!! for maturation
Hox genes regulated by morphogens layers II-VI: form cortical layer > contact-mediated inhibition
= signaling factors: directs cell fate & NEURODEVELOPMENTAL
> chemoattraction
tissue development at a distance from split perplate in: DISORDERS > chemorepulsion
their source > marginal zone = future layer I > spina bifida
→ they induce pattern formation > subplate > anencephaly = underdeveloped B MIGRATION DEFECTS
→ response to morphogen altered by > congenital syphilis & toxoplasma
previous patterning tissue these layers form the 6 layers of cortex > schizophrenia not very !!!, but know that it’s possible
> autism → change in cortex factors?
conserved in many spp. > epilepsy -> migration defects
→ same role & orientation in humans & fruit
flies + very homologue APOPTOSIS DIFFERENTIATION
large part of N during development will be in B >100 ≠ N → how so many?
PROLIFERATION apoptosed > genetically programmed fate choices
→ high regulated + key process in develop- > TF in ≠ stages of development
CNS DEVELOPMENT ment (or combo’s of TF)
see B-development RADIAL GLIA > temporal & spatial segregation
long unknown which cell type produced N caspase 9!!! > environmental factors
NEUROGENESIS IN VZ & SVZ → know now it are radial glia cells: → no caspase = bigger B & more B-defects > conserved genetic programming for
located in ventral part & come from neurogenesis
in lining hollow neuronal tube proliferating
cells neuro epithelium cells
MIGRATION > combinatorial transcription code
= neuronal epithelium cells -> divide → divide in 12-24h in other cells: all radial glia cells = substrates for migration (eg. TbR2)
cells neuro epithelium related → produced N keeps hanging on glia cell for → all specify which N it will become
!!! proliferating marker a while
= phospho histone H3 → uses glia as guide to migrate to HUMAN ORGANOIDS
→ ventral part higher proliferation, but final destination = induced pluripotent cells
most of cortex born in dorsal part = radial migration: nicely oriented → used to model human B-disorders
-> 80% N = glutamatergic N & start from ventricular zone & early stages B-development
-> 20% GABAergic N: regulate → eg. cerebral cortex: inside out
excitatory N formed --> 6->5->4->3->2->1
, NEURONAL POLARITY
N reaches final destination
→ start further differentiation: formation
neuronal polarity with input (dendrite)
& output (axons) zones
→ development axonal growth cone
= extension of developing N looking for
synaptic target
→ highly motile, determines growth
direction & interact with ≠ cells
REFINING CONNECTIONS
initial connections not always good: eg. in-
correct target nucleus
→ need regulation
→ neuronal death, axonal retraction
& synapse elimination
SURVIVAL PRESYNAPTIC
CELL
survival regulated by:
> trophic factors prod. by their targets
= neurotrophines: nerve growth factor,
B derived neurotrophic factor &
neurotrophin 3
• secreted P
• NGF !!!!! for survival in development
• all factors promote N extension,
axonal regeneration & synapse
formation
• act via specific R: TRKs
SYNAPSE FORMATION
axonal filaments when connected
properly change in shape
→ forms: presynaptic element,
cleft (15-30nm) & postsynaptic
elements (with R for NT)
, PAVLOVIAN CONDITIONING THE PLASTIC BRAIN
2 !!! concepts for plasticity:
I. MEMORY SIMPLE LEARNED BEHAVIOR IN MEMORY DEFECT AFTER
II. LEARNING = acquisition knowledge/skills APLASIA
through study, experience or being taught HIPPOCAMPAL DAMAGE
→ 1st scientist that looked at learning Eric Kandel: used sea slug to study learning Henri M.: patient with recurrent epileptic
processes in aplasia seizures
& how behavior changes when you learn
A-B) touch siphon -> redraws gill (yellow) → consulted neurologist Scoville: cut piece
= Pavlov
= preventive mechanism temporal lobe away
→ repeat: slug habituates → helped Henri, but Scoville didn’t know
classical conditioning !!!!: dog -> show dog food
-> saliva production -> proceed presentation → now painful stimuli to siphon: function temporal lobe (hippocampus!!)
food with bell -> after while just bell will faster response (dark blue) DISCOVERY SYNAPTIC
induce salivation (light blue = learning period necessary to store new info PLASTICITY IN HIPPO-
→ after learning period bell induces salivation for touch siphon) → Henri couldn’t learn anything CAMPUS CONFIRMS
= Pavlovian conditioning after operation (even family)
HEBBIAN THEORY
HEBBIAN PLASTICITY & LEARNING & MEMORY IN study: isolated hippocampus & made
CONDITIONING ANIMALS sections
90% work biomedical science done in rats & → put stimulation electrode on Schaffer
psychologist Hebb: though synapse collaterals hippocampus &
connections change as result of experience mice
registration electrode CA1 region
→ 2 cells connected via synapse C) neuronal network of aplasia gill-withdrawal → to look at learning Hampton court maze → start stimulation:
→ use of synapse = synapse efficiency↑ reflex: used = labyrinth
→ nowadays not used anymore: now > low freq. stimulation: gives
→ re-suse synapse: changes efficiency > MN = motor N = withdraws gill same response
& builds information > SN = sensory N = register touch gill Morris water maze
> high freq. stimulation: N goes
> 5HT N= serotonine N = register electric back to initial situation, but
classical conditioning according to Hebb: shock → modulates blue connection MORRIS WATER MAZE
after h the response is
US = unconditioned stimulus = food of SN -> MN B) time needed to reach platform intensified = potentiation
CS = conditioned stimulus → see learning curve: after #days
→ learning process results in change in training animals reach platform faster shows that hippocampus has
connections between cells that register C) memory training Hebbian synapse !!!
ringing bell & N that elicit response → remove platform & see in which
(salivation) quadrant animal was most = synapses that get better when used
→ in end ringing bell = salivation → most time in quadrant where (here high freq. stim. potentiates
→ learning = new connections OR platform was originally ↑ synapses-efficiency)
enhancing existing connections D) shows that learning = based on synapses
→ argument that animal was
→ intervention 5HT N modifies connection synapses -> glutamate R: NMDA & AMPA
really learning !!!
SN & MN → NMDA !!! role in potentiation
D) strategies to find platform:
→ learning process situated at level → why NMDA? -> distributed highly
> spatial: uses higher part of B
modulation synapses in cerebral cortex, hippocampus &
> systematic
> repetitive: no use higher parts B striatum
