MARY ET BOYLE, PH.D. DEPARTMENT OF COGNITIVE SCIENCE

Transcription

1 Neurodevelopment MARY ET BOYLE, PH.D. DEPARTMENT OF COGNITIVE SCIENCE UCSD

2 Brain Development Proliferation Differentiation Migration Axon and dendrite development Synaptogenesis Synapse Pruning Apoptosis programmed cell death

3 Embryonic Brain Development Nervous system develops from ectoderm

4 Properties of Stem Cells Self-renewal Maintain an undifferentiated state after numerous cycles of cell division. Potency The capacity to differentiate into specialized cell types. Totipotent differentiate into embryonic cell types Pluripotent t can differentiate t into nearly all cells Cells are derived from any of the three germ layers. Multipotent can differentiate into a number of cells, but only those of a closely related family of cells. Oligopotent can differentiate into only a few cells Unipotent can produce their own cell type maintain the property of self-renewal.

5 Unipotent Totipotent Multipotent Pluripotent Oligopotent

6 Stem Cells Neural plate cells Appear the have unlimited capacity for self-renewal Totipotent can develop into different mature cell types As the neural tube develops, specificity increases: Multipotent Glial stem cells Neural stem cells

7 Cell Differentiation Single cell Two daughter cells with identical DNA Expression of Neuron specific gene Expression of Epithelialspecific gene Neuron Epithelial cell

8 Differentiation Models: cell autonomous No outside influence

9 Cells differentiate into their distinctive type, e.g. unipolar, multipolar, etc. Image shows Purkinje cells at different developmental ages

10 Differentiation Model: induction

11 The notochord influences some (not all) of the cells in The notochord influences some (not all) of the cells in the spinal cord to become motor neurons. Vitronectin is the chemical that directs them to become spinal motor neurons.

12 Proliferation: Ventricular Zone Ventricular layer lines the inside of neural tube The alar plate gives rise to the sensory neurons. The basal plate gives rise to the motor neurons, sympathetic and parasympathetic nervous system.

13 Migration Neural tube migration Radial migration moving out along the radial glial cells Tangential migration Moving up

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15 Somal Migration Somal an extention develops that leads migration, p g, cell body follows

16 Glial-mediated Migration Cell moves along a radial glial network.

17 Annu. Rev. Cell Dev. Biol :

18 Inside-Out cortical migration

19 Development of Cortex

20 Yuanyi Feng Christopher A Walsh Yuanyi Feng, Christopher A. Walsh Nature Reviews Neuroscience 2, (June 2001)

21 MRI appearance of human lissencephaly and double cortex syndrome. MRI images of cerebral cortex in a normal human being (Normal), a patient with LIS1 mutation (LIS1), a female patient with DCX mutation (DCX-Female) and a male patient with DCX mutation (DCXMale). Notice that patients with mutations in LIS1 and male DCX patients show strikingly similar lissencephalies, whereas female patients with DCX mutations present with double cortex syndrome, in which a band of grey matter is embedded within the white matter beneath the normal cortex.

22 Hooking up - Synaptogenesis Once migration is complete and structures have been formed (aggregation), axons and dendrites begin to extend Growth cone at the tip of each extension, filopodia extend and retract like a cane used by blind person finding their way.

23 Chemoaffinity Hypothesis R. Sperry Postsynaptic targets release a chemical that guides axonal growth Frog retina rotation experiments.

24 Chemical guidance cues

25 Synaptogenesis Formation of new synapses Depends on the presence of glial cells especially astrocytes Chemical signal exchange between pre and post synaptic neurons is needed. Over population of neurons.

26 Immature synapses

27 Activity-dependent synaptic pruning

28 Apoptosis and Synapse Rearrangement 50% more neurons that are needed are produced cell death is normal. Neurons are programmed to die (apoptosis) when they fail to compete for chemicals provided by targets. Increase targets > reduced apoptosis Destroy some neurons > increased survival of remaining cells Increase number of innervating axons > decreased proportion p survive.

29 Life-preserving chemicals Neurotrophins promote growth and survival,,guide axons, stimulate synaptogenesis Nerve growth factor (NGF) Necrosis passive cell death Apoptosis active cell death; much cleaner; better way to go.

30 Cortical Development Age 4-21 Gogtay et al PNAS

31 Postnatal cerebral Development in Infants Postnatal growth is a consequence of: Synaptogenesis Myelination sensory areas then motor areas Myelination of prefrontal cortex continues into adolescence Overproduction of synapses may underlie the greater plasticity of the young brain.

32 Effects of Experience: deprivation Early visual deprivation Fewer synapses and dendritic spines in 1 visual ctx. Deficits in depth and pattern vision

33 Effects of Experience: enrichment Thicker cortices Greater dendritic development More synapses per neuron

34 Neurogenesis Old dogma: no new neurons after infancy 1960 s: evidence of cell proliferation in adult hippocampus and olfactory bulb (J. Altman) 1980 s: discovery of neurogenesis in adult male canaries (Nottebohm) 1990 s: neurogeneis occurs throughout lifespan in many species, including humans!

35 Neurogenesis Dentate gyrus of the hippocampus Subventricular zone of the cortex Associated with: Environmental enrichment Exercise Memory formation

36 Adult Neurogenesis in Humans Erikson et al 1998 Nature Medicine