Nervous System Development Flashcards
1
Q
Primary Vesicles
A
Appears during the 4th week of development.
Rostral ⇒ Caudal
- Prosencephalon → forebrain
- Mesencephalon → midbrain
- Rhombencephalon → hindbrain
Two flexures present in the neural tube at this stage:
-
Cephalic flexure
- Occurs at the level of the future midbrain
- Retained in bipedal organisms
-
Cervical flexure
- Occurs between the rhombencephalon and caudal spinal cord
- Straigtens out later in development
2
Q
Secondary Vesicles
A
Appears during 5th week of development.
Two primary vesicles become subdivided.
Rostral ⇒ Caudal
- Prosencephalon:
-
Telecephalon (cerebrum)
- Cerebral hemispheres
- Basal ganglia
-
Diencephalon
- Thalamus
- Hypothalamus
- Retina
-
Telecephalon (cerebrum)
-
Mesencephalon: does not become subdivided
- Midbrain
- Rhombencephalon
-
Metencephalon
- Cerebellum
- Pons
-
Myelencephalon
- Medulla Oblongata
-
Metencephalon
A third flexure develops in additional to the previous two:
- Cephalic → ventral mesencephalon
-
Pontine → dorsal surface between Metencephalon and Myelencephalon
- Is not retained
- Important in development of caudal brainstem
- Cervical → ventral surface between Myelencephalon and spinal cord
3
Q
Major Developmental Events
A
-
Neurulation
- The process by which the neural tube is formed
- Includes formation of the neuraxis (flexures)
- Occurs between 3-8 weeks
-
Neuronal Proliferation and Migration
- Occurs between 8-16 weeks
-
Synapse Formation and Myelination
- Occurs between 16-40 weeks
- Under a significant amount of environmental influence
4
Q
Primary Neurulation
A
Occurs during 3rd and 4th week of embryonic development.
- Band of ectoderm thickens
- Ectodermal cells form the neural plate
- Neural plate folds in medially to form neural groove between neural folds
- Neural groove fuses to form the neural tube
- Closure starts in the center ⇒ both rostral and caudal
- Neural tube develops into the CNS
- Cavity becomes the ventricular system
- Group of cells from crest of each neural fold dissociates from the neural tube ⇒ neural crest cells
- Cells develop into a variety of cell types including:
- sensory neurons of ganglia of spinal nerves
- postganglionic neurons of the ANS
- Schwann cells of the PNS
- Cells develop into a variety of cell types including:
5
Q
Three Vesicle Brain
A
During the 4th week of development:
- Neural tube enlargements appear forming the three primary vesicles ⇒ three vesicle brain
- Proencephalon
- Mesencephalon
- Rhombencephalon
- Cephalic and cervical flexures develop
6
Q
Five Vesicle Brain
A
During the 5th week of development:
- Proencephalon and rhombencephalon become subdivided forming the five secondary vesicles ⇒ five vesicle brain
- Telencephalon
- Diencephalon
- Mesencephalon
- Metencephalon
- Myelencephalon
- Pontine flexure develops dorsally
- Dorsal and ventral segments of neural tube thicken disproportionately
- A longitudinal fissure appears along the lateral wall of the neural tube ⇒ Sulcus limitans
- dorsal portion ⇒ alar plate
- mainly sensory (afferent) derivatives
- ventral portion ⇒ basal plate
- mainly motor (efferent) derivatives
- Specific neural modalities (visceral, somatic, special) have characteristic locations within alar/basal plates and subsequent dorsal/ventral horns of spinal cord
- Similar orgainziation exists in the brain stem
- Sensory nuclei lateral
- Motor nuclei medial
- dorsal portion ⇒ alar plate
- Sensory ganglia, basal ganglia, thalamus, and hypothalamus begins to develop
7
Q
Neural Tube Closure
A
- Closure begins in the region of the 4th to 6th somites at around day 22
- Proceeds both cranially and caudally
- Rostral neuropore (cranial opening) closes by ~ day 25
- Caudal neuropore (caudal opening) closes by ~ day 27
8
Q
Rachischisis
A
Defects in neural tube closure.
- Location and extent of neural tube defects (NTD) vary
- Causes:
- Some genetic predisposition
- Teratogens
- Alcohol
9
Q
Anencephaly
A
- Failure of rostral neuropore to close
- Results in subsequent brain under-development and incomplete skull formation
- Fetus rarely survive and frequently terminated
10
Q
Spina Bifida
A
Developmental defects in caudal vertebral column, meninges, and/or spinal cord.
-
Spina bifida occulta
- Bony vertebral defect only seen via XR or MRI
- Skin dimpling or hairy patch may appear at base of spine
- 5-10% of general population
-
Open spina bifida
- Meninges, spinal nerves, or spinal cord connected to overlying skin
- 50/100,00 births
- Two types:
-
Meningocele
- Meninges are fused with overlying skin in pouch containing CSF
- Can usually be surgically repaired
-
Myelomeningocele
- Failure of caudal neuropore closure
- Pouch also contains spinal nerves or spinal cord in most severe cases
- Surgical repair difficult
- Most non-ambulatory
-
Meningocele
11
Q
Holoprosencephaly
A
- Failure of the prosencephalon to differentiate into forebrain and diencephalon
- Occurs during 2nd month of gestation
- Rostral neuropore closure was normal
- Very rare
12
Q
Secondary Neurulation
A
Begins during 4th week and completed 6-7th week of development:
- After neural tube closes, secondary cavity forms at the caudal end of the neural tube ⇒ secondary neurulation
- Develops into the scaral spinal cord
- During this time enlargement of specializations of neural tube also occurs
- telencephalon
- cerebellum
13
Q
Fourth Ventricle Formation
A
- Pontine flexure development forces walls of the neural tube apart forming a diamond shaped cavity
- Only thin membranous roof covers future site of 4th ventricle
- Alar and basal plates rest at the floor of the 4th ventricle
- Eventually forms part of the adult brainstem ⇒ rostral medulla & caudal pons
- Sensory nuclei laterally located
- Motor nuclei centrally located
14
Q
Neurulation
Late Stage
A
Occurs during the 8-12th weeks of development:
-
Reflexes appear caudally
- Suggests interconnection of sensory and motor pathways in spinal cord
- Major development of complex structures at rostal end
- Neuronal proliferation and migration in the cerebral and cerebellar cortex
- First cortical sulci appear
- Glia begin to differentiate
15
Q
Neuronal Proliferation and Migration
A
Occurs during the 8th - 16th weeks of development
Timing of a neuron’s final division (birthday) determines migratory site.
Location determines function.
Migration guided by radial glial cells which extend from ventricular zone to surface of the marginal layer.
-
Thalamus
- Occurs in an “outside-first” order
- First neurons to reach their birthday migrate to outermost portion of the thalamus and mature there
- Neurons with later birthdays migrate to more medial locations
-
Cerebral & Cerebellar Cortices
- Occurs in an “inside-out” pattern
- First cells to migrate located in ventricular zone
- Cerebral cortex formed by expansion of superficial part of intermediate zone into the subplate and cortical plate.
- Final neuroblasts located closer to pial surface.
16
Q
Neuron Death
A
- During first 24 weeks of gestation:
- Twice as many neurons generated than found in mature brain
- Large number of degenerating neurons undergoing apoptosis appears during this period
- Reason for overproduction then elimitation unclear
- May be related to strict requirements for specific connectivity patterns during different stages of development
- Cells with potential problems eliminated
- Mature patterns of required for function dependent on:
- final location of neurons
- early synapse formation
- dendritic development
- formation of axonal branches
17
Q
Factors Determining
Neuron Connectivity and Function
A
- Mature patterns of connectivity required for neuronal function dependent on:
- final location of neurons
- early synapse formation
- dendritic development
- formation of axonal branches
18
Q
Microcephaly
A
Decreased brain size due to defect in neuronal proliferation.
Skull is also smaller due to brain size.
19
Q
Lissencephaly
A
“Smooth Brain”
- Decrease or absence of sulci and gyri in the cerebral cortex
- Normally associated with microcephaly
- Due to defect in neuronal migration
20
Q
Pachygyria
A
“Thick Gyri”
- Gyri are broad, shallow, and decreased in number
- Due to defect in neuronal migration
21
Q
Polymicrogyria
A
Characterized by numerous small gyri
Due to interference in neuronal migration
22
Q
Cortical Heterotopias
A
Misplaced neural tissue.
- Characterized by islands of neurons in abnormal location along migration route due to arrest in migratory process
- Extent of heterotopias determines severity
- In mild cases, neurons typically able to find appropriate location eventually
- Usually see seizures
23
Q
Toxic Exposure
During 3rd Month of Gestation
A
- Exposure of embryo during 3rd month to:
- alcohol
- radiation
- drugs which affect monoamines i.e. cocaine
- Results in:
- Major abnormalities in lamination
- Decreased cell numbers in cortex
- Subsequent synaptic disorgainzation
24
Q
Axonal Outgrowth
&
Synapse Formation
A
Occurs during 16th-40th weeks of development.
Characterized by prolific synaptogenesis.
- Neuron at their final destination extend a single axon with specialized growth cones at the end.
- Many molecular cues guide the growth cone to appropriate destination
- Tropic factors from the target
- Trophic factors which sustains the cells
- Axonal branches may be formed in excess
- Extra or innappropriate branches eliminated
- Many molecular cues guide the growth cone to appropriate destination
- Once growth cone reaches destination, undergoes changes to form presynaptic terminal.
-
Target neurons begin expressing postsynaptic changes.
- Development of neurotransmitter receptors
- Secondary messenger formation
- During this period:
- neuronal migration continues
- Glia proliferate
- myelination begins
25
Q
Axonal
Guidance Cue Relationships
A
- Cooperation
- Crosstalk
- Additivity
- Synergy
- Fine-tuning
- Combinatorial signaling
- Hierarchical
26
Q
Fetal Alcohol Syndrome
(FAS)
A
-
Neuron survival
- Triggers widespread apoptotic neurodegeneration during the 3rd trimester
- Occurs via:
- Transient blockage of NMDA receptors (glutamate N-methyl-d-aspartate)
- Excessive elevation of GABAA receptors
-
Axon growth
- Corpus callosum absent in many patients with FAS
- Blocks binding of axonal adhesion molecule L1 with substrate (L1CAM)
- Critical for interactions during axonal growth
27
Q
Known
NMDA antagonist and GABAA agonists
A
- Alcohol
- Certain sedatives and anesthetics
- halothane
- isofluorane
- nitrous oxide
- ketamine
- Seizure medications
- Anxiolytics
- barbiturates and benzodiazepines
- Phencyclidine (angel dust)
28
Q
Effects of Experience
A
Sensory and motor abilities of the neonate reflect functional pathwyas in sensory and motor systems present at birth.
“Fine tuning” of synaptic connectivity occurs late prenatally and postnatally.
Dependent on chemical environment and environmental stimuli throughout first years of life.
29
Q
Binocular Vision
Environmental Effects
A
-
Normal:
- Early, visual axons branch extensively at several points
- Later, axon terminals concentrated in a single region
- Most axons responsive to stimuli from both eyes
- Necessary for binocular vision
-
Sensory deprivation:
- One eye is blocked so light seen but not shapes
- Deprived eye shows dramatic reduction in axonal arbor development
- Once deprivation removed, neurons respond to one eye or the other but not both
30
Q
Visual Processing
Environmental Effects
A
- City dwellers:
- Frequently exposed to buildings with vertical and horizontal lines
- Results in higher visual acuity with horizontal and vertical orientations
- Cree Indians:
- Exposure to curved and oblique orientations
- No preferential visual acuity
31
Q
Developmental Plasticity
Auditory System
A
- Cochlear implants
- converts speech to electrical impulses
- impulses stimulate auditory nerve
- central auditory neurons learn to recognize impulses as words
- Efficacy depends on age of implantation
- Best before 5.6 y/o
- See improved word understanding and comprehesion
- Likely related to dendritic development
- Increased with environmental stimuli
- Decreased with stress
32
Q
Myelination
A
- Starts around 6th month of gestation
- Continues through 3rd decade of life
- Oligodendrocytes responsible for myelination in the CNS
- Responds to environmental factors well beyond developmental time frame in adult brain
- Degree of myelination measured through water diffusion patterns:
- Isotropic = non-myelinated
- Anisotropic = myelinated
33
Q
Environmental Control
Emotional Development
A
Amygdala responsible for emotion.
Prefrontal cortex responsible for control of emotion.
- Brain activity in these regions measured in high risk and low risk individuals
- High risk = poor familial background
- Low risk = good familial background
- Participants asked to:
- Look at cross hairs = control
- Judge emotion
- Judge gender
- Observe Response:
- Cross hair fixation subtracted for baseline activity
- High risk individuals showed less activity in the amygdala
- Emotion:
- Subtracted assign gender for baseline activity
- High risk individuals showed greater amygdala but lower prefrontal cortex activity
- More emotional and less control
Interpretation: Risky childhood leads to establishment of intra-cortical wiring for avoidant coping responses as well as difficulty regulating emotional responses.
