S1W11Dev Flashcards
Step 1 neural tube from a neural plate
Neural plate = 16 day gestation.
Neural tube = 22 day gestation.
NT closes and forms brain and spinal cord = 27 days gestation.
Centre of NT becomes ventricles of brain filled with CSF.
Neural progenitor cell
Line inner part of NT.
Differentiates into specific type of cell, but is already more specific than stem cell.
Some cells separate to form the neural crest which makes the PNS.
Cerebrospinal fluid (CSF)
Fills centre of CSF.
Mechanical and immunological protection to brain.
Neural tube defects causes
Neural tube fails to close properly
Exposure of part of brain and/or spinal cord
Varying degrees of bone and neurological involvement (can be fatal)
Craniorachischisis
Completely open brain and spinal cord.
Fatal.
Anencephaly
Open brain lack of skull vault.
NT fails to seal at the head of embryo.
Forebrain fail to develop.
Fatal.
Encephalocele
Herniation of meninges and brain.
Retardation and vision problems.
Iniencephaly
Occipital skull and spine defects with retroflexion of head.
Fatal.
Meninges
Membranes
Spina bifida
Neural tube fails to seal at lower end.
Different types.
Spina bifida occulta
Some vertebrae not closed.
No cord protrusion .
Symptomless.
50% of population have it and are unaware.
Closed spinal dysraphism
Deficiency of 2+ vertebral arches.
Unlikely to cause problems on its own.
Meningocele
Protrusion of meninges through skull or spine defect.
Mild problems.
Filled with CFS and not spinal cord parts.
Myelomeningocoele (Open spina bifida)
Protrusion of spinal cord.
Severe complications.
Poor walking, bowel control.
Step 2 (1) (three vesicles)
Cranial (front) part NT becomes (5 weeks):
Hindbrain (rhombencephalon)
Midbrain (mesencephalon)
Forebrain (proencephalon)
Caudal (back) part NT becomes spinal cord.
Fluid fills spinal cord canal and ventricles.
Further division of three vesicles
Vesicles enlarge and divide into:
Forebrain:
Telencephalon
Diencephalon
Midbrain:
Mesencephalon
Hindbrain:
Metencephalon
Myelencephalon
Telencephalon
Cerebral cortex
Basal ganglia
Diencephalon
Thalamus
Hypothalamus
(forebrain)
Mesencephalon
Colliculi
midbrain
Metencephalon
Pons
Cerebellum
(hindbrain)
Myelencephalon
Medulla
hindbrain
Forebrain
Cerebrum
Thalamus
Hypothalamus
Hindbrain
Pons
Medulla oblongata
Cerebellum
Step 3 – Neuronal development
Walls of NT contain stem cells, which drive brain growth by dividing.
Stages: • Proliferation • Migration • Differentiation • Synaptogenesis • Myelogenesis
Stem cells
Undifferentiated cells that differentiate into specialised cells or divide (mitosis) to produce more stem cells.
Proliferation
42 days gestation.
Neural progenitor cells either:
- Stay in choroid plexus.
- Continue to divide into neurons and glial cells.
Peak proliferation rate = 250k neurons/minute.
22 weeks gestation neurogenesis complete apart from olfactory bulb hippocampus.
Glial cells
Surround neurons and hold them in place.
Supply oxygen and nutrients to neurons
Destroy pathogens/dead neurons.
Migration
Neural progenitor cells migrate at different rates and directions, aiming to reach the target cell in up to four days.
Migrate up to 2cm.
Sperry’s Newt (1940)
How do cells know where to go?
Cut optic nerve of newts and rotate the eye 180 degrees.
Axons grew back to original places but newts saw upside down.
Axons are guided by gradient of proteins called neurotrophins.
Numerous synapses made in target then synaptic pruning removes.
Differentiation
Neural progenitor cells take on characteristics of specific neuron.
Formation of axon and dendrites.
Acquisition of enzymes to produce neurotransmitters.
Acquisition of receptors to receive synaptic transmissions.
Synaptogenesis
Formation of synapses
Lifelong but slows with age
1-2yo – peak synapse formation - twice as many connections as adults.
Synaptic pruning
Axon differentiation
Grows first
Tip of axon = growth cone (site of elongation and extension).
Growth cones sample local environment for molecules that direct growth.
Axons can grow whilst migrating.
Dendrite differentiation
Grows once neuron reaches target.
Grows slower than axons.
Myelogenesis
Myelin surrounds axon forming insulating sheath
Oligodendrocytes form myelin in CNS (Schwann cells in PNS).
Process: Spinal cord > Hindbrain > Midbrain > Forebrain • Takes years
Other functions of oligodendrocytes
Produce trophic factors that maintain axonal integrity and neuronal survival.
Neuron/Oligodendrocyte interactions influence neuronal size and axon diameter.
Regressive events in neuronal development
Brain overproduces: o Neurons (peak at 7mo) o Synapses (peak at 1-2yo at 15,000)
Regression results in thinning of cortex associated with behavioural development.
Apoptosis and Pruning.
Apoptosis (programmed cell death)
Prenatal.
Reduces neurons
Results in loss of cell and all synapses
Neuron dies
Maximal during late prenatal stage (reduces 28bil to 23bil by birth)
Triggered by lack of neurotrophins released from postsynaptic cell.
Synaptic pruning
Postnatal
Reduces synapses
Neuron survives
Three methods:
o Axon degeneration
o Axon retraction
o Axon shedding
All result in axon removal and deletion of synapse
Triggered by hormones and neurotrophins.
Hebb Rule (1949)
What determines which synapses are pruned?
States that the connections between two neurons might be strengthened if the neurons fire simultaneously.
Embyronic stage development
Conception to week 8 gestation.
Rudimentary structures of brain produced
Major compartments of CNS and PNS defined
Neuron production starts at week 6 gestation
Foetal stage development
Week 9 gestation to birth
Characteristic pattern of gyral and sulci folding.
Development of neocortex.
Neurogenesis, migration and differentiation.
Neuronal cell loss.
Newborn brain
One quarter of adult size
Spinal cord and brain stem well developed
Limbic system and cerebral cortex still primitive
Birth to toddler years
Synaptogenesis in cerebral cortex(exuberant period)
At peak cerebral cortex creates 2 million synapses/second.
Corresponds with mental milestones
Myelination rapid in first 2 years.
2yo - brain 80% of its adult size
Toddler to adolescent
Too many synapses in cerebral cortex in childhood
Synaptic pruning increases 4-6yo
Brain 90% adult size by 6yo
Adolescence (13-18yo)
Synaptic pruning until end of adolescence
Grey matter decreases in volume
Myelination continues especially in frontal cortex
White matter increases in volume
Prefrontal cortex matures later than limbic system
Creates neural imbalance
Theorised to be one reason for teen impulsiveness
Brain adult weight
End of adolescence to 60s
Brain peak power at 22yo for 5 years
Then:
Cortex becomes thinner
Myelin sheath degrades
Decrease in plasticity
Decrease memory, reasoning, spatial skills and thought speed
Changes minimal in healthy individuals
60s onwards
65+ years elderly for experiments
Brain shrinks in size
Myelin sheath degrades
Blood flow to brain decrease
Damage by free radicals increases
Decrease in memory, ability to learn, attention, reasoning.
Dementia
Vascular (20-30%)
Lewy Bodies (10-25%)
Frontotemporal (10-15%)
Alzheimer’s (50-75%)
Anatomically:
Plaques (outside neuron)
Tangles (inside neuron)
Nature vs. Nurture
Nature:
Genes guide brain set-up
Provide information for cells and general connections
Nurture:
Experience responsible for fine tuning
Prenatal nutrition
Maternal diet important
Low calories = decreased foetal neural development
Low Omega 3 = poor infant neural development
Severe maternal iodine deficiency = mental deficiency (cretinism)
Postnatal nutrition
Child’s own diet important
Iron deficiency = poor STM encoding or retrieval
Inadequate calories and protein = smaller brains due to reduced dendritic growth, myelination and glial cells
