Neurodevelopment Flashcards
Name 2 methods of studying circuit plasticity
Confocal single-photon microscopy, 2-photon microscopy
Describe confocal microscopy
Individual neurons are labelled with a fluorescent protein, and the emitted fluorescence is detected and envisaged with the microscope
Give an advantage of 2-photon microscopy over confocal microscopy
It is more precise, allowing the fluorescence to be detected in a smaller sample area
Describe Xu et al’s 2009 experiment into synaptic formation and learning in mice
Xu et al taught mice to run on a rotating pole and used a microscope to monitor changes in synaptic connections in the motor cortex. They found that dendritic spine formation and stabilisation was induced in motor control areas but not neighbouring areas
Describe Lu et al’s 2015 experiment proving that new synaptic connections are essential for learning
Lu et al taught mice to run on a rotating rod, with motor neurons stained green to allow identification. They studied the development of new connections, then used a laser to remove only the new connections. Removal of the connections caused the mice to start falling off the rotating rod
Summarise the process of neurogenesis of the human brain
Cortical progenitors form deep layers first, then cortical pyramidal neurons, then upper cortical layers. Finally, cortical progenitors become astrocytes
How long does cortical development take in the human brain?
22 weeks - from gestational week eight to week thirty
Why are synapses hard to visualise in neuron cultures?
Connections may not form effectively in vivo, and neuron cultures are only bidimensional, which likely affects development
Describe cerebral organoids (Lancaster et al, 2013)
Induced pluripotent stem cells are directed to form an organised tissue
State some limitations of cerebral organoids for studying the brain
In vitro models, no vasculature so no supply of nutrients (cell death after a month), not representative of the human brain
Describe the results of Espuny-Camancho et al’s 2013 experiment on ex vivo neurons
They transplanted human neurons from stem cells into a mouse brain, where they produced neurons with dendritic spines that more closely resembled those in post-mortem human brain tissue than any previous culture method
Describe the results of Livesey & De Paola’s experiment into ex vivo neurons
Human neurons spread from the injection site and colonised the mouse brain, developing complex cytoarchitecture similar to that in post-mortem human foetal cortices. The human cells grafts were highly vascularised by the mouse and exhibited elongation and retraction, confirming development involves making excess branches then pruning and refining them
Name a disease modeled by ex vivo studies
Down syndrome
State some developmental brain defects in Down syndrome
Reduced brain volume, impaired neurogenesis, impaired dendritic development, impaired synaptogenesis
State some limitations of mouse models of Down syndrome
Rodents do not have a chromosomr 21, mouse models are partially trisomic for distinct sets of genes, the Down syndrome phenotype is influenced by global transcriptome dysregulation (Antonarkaris et al, 2004)
