Neuronal Development Flashcards
Neurogenesis
When progenitor cells undergo mitotic division and produce new stem cells or neuroblats they will differentiate into neurons
Process of neurogenesis
Dividing precursor cells from ventricular zone - some leave and form marginal zone and intermediate layer layer forms these neurons develop into glia and neurons
As no of cells increases cells must migrate along frail glia
When cells reach destination they begin to definterate
Process outgrowth - dendritic and axon Growth and proliferation of synapses
Stages of nervous system development
L
Neurogenesis- mitotic production of neurons from non neuronal cells
Cell migration- movement of cells to establish distinct populations
Differentiation- transformation of precusor cells to distinctive neurons or glia
Synaptogeneus- synaptic connections
Neuronal cell death- selective death of many nerve cells
Synapse rearrangement - loss or development of synapses
Critical period and theory
Between childhood and adolescence - defined as window which sensitivity to sensory stimuli is temporarily heightened and promotes changes in connectivity
Theory- explains decline in synaptic dynamics during brain development and understanding pathogensis if asd
Neural tube formation
Medial neural hinge point cells anchor to notochord and change shape
Epidermal cells move to centre
Neural gold elevated while epidermal cells continue to move to midline
Neural fold converge as Dorsolateral hinge point cells become wedge shaped
Neural folds are brought together and crest cells link the neural tube with epidermis
Crest cells disperse and tube separates (forms)
Where are crest cells formed
Along most of anterior-posterior axis of the embryo from posterior diencephalon to lunbosacral region of embryo
Grouped according to position of spinal
What are SHH cells
Morphogen secreted by the notochord which is required for development of midline structures and then for dorsoventral specification of the neural tube
What determines neuron type differntation
Conc of SHH- more is motor neuron
More BMP is sensory neuron
What projenitor cells are made by neurogenesis
Apical progenitors- mitosis near ventricle and can turn into radial glia
Basal- migration scaffold
Subapical- same as apical but can u deffo mitosis anywhere
When does neurogeneis begin
When projenitor cells switch from symmetric to asymmetrical cell division
What become pyramidal cells
Apical and basal projenitor in ventricular and subventrucular zone
How is neuronal growth guided
Growth cones at the end of axons
Spiny bodies sense environment
They avoid contact with unfavourable surfaces and remain on favourable ones
Form synapses at target cells
Must retentive enough neurotrophic factor secreted from target cell to survive
Sema3
Dorsal root ganglia are repelled by sema - when neurophorin is knocked out they loose sensitivity to sema3f but not 3a
Okay a key role in projection- acts as receptor by acting ligands and transmitting signals to expressing cells
What are mechanisms of synaptic connections
Topography-refining dendrites
Convergence- reducing two converging synapses to one
Post synaptic component - cut post synaptic to just pre
Synapses during development
Functional synapses are eliminated during development
Larger stimulation= larger post synaptic potentials in immature neurons. At end of maturation process only one axon remains connected
Spontaneous movements of embryo
Movements of embryo cause correct synaptic connections and refinement of synapses when animal opens eyes
Spontaneous activity propagates rostral my in cortex
How can you view pattern of innervation in eyes
Inject dye in one eye and can see pattern of innervation in layer 4 of cortex. Innervates in stripes I’m response to light- also seen in LGN
What can cause stripes not to develop
If the spontaneous activity in the retina that occurs before the eye opens is blocked by TTX
How should activity occur in eye for best correlation
Synchronous stimulation means domain of overlap is increased in LGN in both sides but asychnorous activity there is less overlap . The correlation between two retina determine the pattern of synaptic refinement . Too correlTed means no segregation between two eyes
How come excitatory blocking doesn’t stop episodic activity in the eye
There are compensatory mechanisms but they aren’t necessary because immature cells have high cl levels inside the cell so GABA causes a large cl movement out of cell that causes depolarisation
Cl is high because there’s a high expression of NKCC1 brings cl into immature cells
As the neuron matures it switched to KCC2 as the dominant transporter which moves cl out of the cell
What happens to synaptic potentials after an episode
It increases before episode then decreases . The spread of waves is limited in the retina by refractories . If second wave appears it won’t propogate in the depleated /same areas
Slow negative feedback
What determines episode duration
Interval time
Duration increases with interval time
Correlated with length of proceeding interval but not the following
What amplitude do episodes return to
Zero
Why are developing networks excitatory
Early in development GABA and glycine are functionally excitatory
That means fast feedback
Causes of asd
Single gene disorders
Metabolic disorders
Unknown like nutrition, pollution etc
Subgroups of genetic asd classification
Post synaptic density - synaptic function and transmission of nts
Chromatin modification and regulation
(epigenetics)- dysfunction
Neuronal signalling and cytoskeleton
Channel activity
Mechanisms that contribute to development of guiding of growth comes
Contact attraction
Chemoattraction
Contact repulsion
Chemo repulsion
Pluripotent stem cells different during asd
Double in number faster
Less time in growth phase
Greater proliferation correlated with brain overgrowth
Synapses in asd
Change or variation in some synaptic formation genes
Synaptic elimination- reduces synaptic contacts
Maintenance of unnecessary synapses in asd - lack of synaptic pruning
Causes Overlap of firing which leads to over sensitivity to light or sound
Asd has hyper connectivity in Brain and more synapses in many regions - over excitation and imbalance between more excitation and inhibition
Fragile x syndrome asd
Genetic condition
Intellectual disability
Features of asd
Physical features like long ears and face
Causes by gene repeat expansion of FMRI gene that codes for fmrp
What is fmrp
RNA building protein that inhibits mRNA translation - located in dendrites abs synapses
What happens if fmrp is lost and what treats it
Excessive protein synergies and altered spine morphology and synapse function - density of spines increase
Inhibition of mglur5 protein corrects fmrp knockout mice - it inhibits direct pathway to prevent over stimulation of movement
What asd symptoms can you measure in animals
Social interaction
Communication
Repetitive behaviours
Impairments in Alzheimer’s
Day to day memory
Concentrating, planning
Language
Visio spatial skills
Spatial orientataion
Changes to wave bands during dementia
Decreased alpha frequency and increased power in theta and delta bands - seen by EEG
changes in eeg are well correlated to the degree of cog impairments
Progression through brain of Alzheimer’s
Starts and hippocampus and moves to frontal areas
What does 4 mountains task show
Asses spatial memory and is a good marker to show dementia pathology
Performance is correlated to degree of hippocampal atrophy
Place and grid cells in dementia
Place cells have decreased spatial info in dementia
Grid cells dissapear
What is epilepsy
Group of neurological disorders that exhibit periodic seizures
Occurs from an imbalance between excitation and inhibition (glu and gaba)
What are seizures
Associated with high frequency discharge impluses by a group of neurons in the brain
What are the types of seizures
Tonic-clonic= person jerks and May loose consciousness and control
Absence = person looks to be dreaming or blank for a few seconds and unresponsive- person is unaware
Parietal/focal= abonornal actuvity in only one area - still consciousness (simple) or not conscious (complex)
What constrains speed and extent of seizure propagation
Feed-forward inhibition
How do seizures affect gaba
During seizures gaba can switch to excitatory
- kcc2 takes cl out of cell making gaba inhibitory
Nkccl moves cl into cell an makes gaba excitatory. When gaba is activated it causes cl to move out leading to depolarisation
During seizures you can see increasing cl levels in cell and gaba starts depolarising cell. And inhibition of gaba leads to hyperpolarising
What happens to cell after seizure
Minutes after seizure there is post translational downregulation of kcc2
Hours to weeks after - genomic downregukation if kcc2 means that it’s more likely to experience hyperexcitability in the future
