Plasticity & Regeneration Flashcards
How is gene expression determined?
- Inducing factors (signalling molecules provided by other cells)
- freely diffusible, exerting action over large range or;
- tethered to cell surface, act locally
* *Responsible for differentiation and patterning of developing neurosis - Competence (the ability of a cell to respond to inducing factors) which is dependent on:
- exact set of surface receptors (study of these in animals is molecular basis of human neurological conditions)
- transduction molecules
- transcription factors expressed by the cell
Neurogenesis is the process by which neurons are generated.
When does it occur?
What are neural stem cells?
Neural progenitor cell?
Neuroblast?
Occurs between 5th week-5th month of embryology
Peak rate: 250,000 neurons/minute
Neural stem cells
- infinitely self renewing
- after terminal differentiation they can give rise to full range of cell classes WITHIN RELEVANT TISSUE (e.g. inhib/excit. neurones, astrocytes, oligodendrocytes)
Neural progenitor cells
- Incapable of continuing self-renewal
- Give rise to 1 class of differentiated progeny e.g. inhib neural progenitor cell give rise to inhib neuons UNTIL its mitotic capacity is exhausted.
Neuroblast
- Postmitotic, immature nerve cell than can differentiate into a neuron
- Fate determined by age of precursor cell, position in ventricular zone, environment and time of division
Outline the steps involved in neural cell division
- In G1, nucleus is near ventricular surface
- In S stage, nucleus and surrounding cytoplasm migrate toward pial surface and DNA replicates
- In G2, cell grows and nucleus migrates toward lumen again
- In mitosis, cells lose connection to pial surface and divide.
Symmetrical divisions generate two neural stem cells. Asymmetrical divisions generate a neuroblast and progenitor cell with limited mitotic potential
Consider neuroblast differentiation
How does the neuroblast differentiate?
Differentiation structure of neuroblast (looks like arm with star as hand):
Axon- contains microtubules
Growth cone- contains actin filament which form actin bundles, filopodium (star point), lamelipodium (web between starpoints)
Differentiation involves:
- Pathway selection (e.g. retinal ganglion cell reaching the correct thalamic location)
- Target selection (e.g. selecting the appropriate thalamic nucleus, LGN)
- Address selection (e.g. which LGN layer)
How does the protein distribution differ in neural stem cells, progenitor cells and neuroblasts?
The proteins notch-1 and numb are differentially distributed in the precursor cells of the developing neocortex. Vertical cleavage partitions these proteins equally in the daughters, but horizontal cleavage does not. Differences in the distribution of proteins in the daughters causes them to have different fates.
Vertical cleavage gives rise to 2 identical neural stem cells
Horizontal cleavage gives rise to a neuroblast (who will migrate away) and a progenitor cell with limited mitotic potential
How is the cortex developed?
Inside-out development
-Inside develops first and outside last
Consider neuroblast differentiation
What guidance cues exist and what do they do?
There are four mechanisms of axon guidance.
Chemoattraction-Axons growing toward a secreted attractive cue preferentially grow toward the source, extending up a concentration gradient.
Chemorepulsion- Axons that encounter a secreted repulsive cue preferentially turn and extend away from the source of the cue.
Contact-mediated attraction-Axons that encounter substrate-bound attractive cues preferentially extend along the surface of those cells.
Contact mediated repulsion-Axons that encounter substrate-bound repulsive cues retract their growth cones, resample the environment, and preferentially extend on cells expressing different cues
Consider neuroblast differentiation
Give an example of a neurotrophic factor?
How do their interactions aid in the formation of the CNS and PNS?
Neurotrophic factors e.g. nerve growth factors
Apoptosis: reflects competition for trophic factors and produces the proper match in the number of presynaptic and postsynaptic neurons
Give an example of a molecule that plays a role in chemoattraction
The protein netrin is secreted by cells in the ventral midline of the spinal cord. Axons with the appropriate netrin receptors are attracted to the region of highest netrin concentration.
Give an example of a molecule that plays a role in chemorepulsion
The protein slit is also secreted by midline cells. Axons that express the protein robo, the slit receptor, grow away from the region of highest slit concentration. Up-regulation of robo (Slit receptor) by axons that cross the midline ensures that they keep growing away from the midline.
Consider synaptic elimination
Explain Activity-dependent fine-tuning of neuronal connections as an example of synaptic capacity
When is this important?
Initially each muscle fibre receives inputs from several alpha motor neurons. Over the course of development, all inputs but one are lost. Normally, postsynaptic AChR loss precedes the withdrawal of the axon branch. Simply blocking a subset of receptors with α-bungarotoxin can also stimulate synapse elimination
Activity-mediated influence on the developing brain is most consequential in early life, during temporal windows called critical periods.
What is the critical period concept?
What is required for successful completion?
Variable time window for different skills/behaviours e/g/ sensorimotor skills, language acquisition, visual perception, emotional functions
Successful completion requires:
- Availability of appropriate influences (e.g. exposure to language)
- Neural capacity to respond to them
Experience during a critical period changes the way the brain is wired and how individual neurons respond to stimulus
The first steps in constructing brain circuitry rely largely on intrinsic cellular and molecular mechanisms such as…
Establishment of distinct brain regions
Neurogenesis
Major axon tracts
Initiation of synaptogenesis
Guidance of growing axons to appropriate targets
How is ocular dominance observed in layer 4 of V1?
What is visual deprivation concept?
Radioactive amino acids injected in eye
Transynaptic transport through the LGN terminated in layer 4 of the primary visual cortex
Terminations are visible as bright bands on the autoradiogram
Development of visual perception requires sensory experience. Effects ocular dominance
Why do critical periods end?
What is this important?
Various hypotheses?
- Axon growth
- Synaptic transmission maturures
- Constraint cortical activation
Important for understanding recovery from damage
