Chapter 23- Wiring of the Brain PDF

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Professor Julia Peterman...

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Chapter 23- Wiring of the Brain The wiring of the visual system  Complicated pathways  Precise layering  Neurons are organized by the o Ganglion cell type o Where the info is coming from o Retinotopic position  Where the cells are in the retina How did such a precise wiring arise?  Brain comes from the neural tube in fetal development  Impacted by both environment and genes The genesis of neurons  Step one of wiring the nervous system is the generation of neurons  Adult striate cortex o 6 layers o Each have distinct neurons  Separates them from other neurons/layers o Neuronal structure develops in three major stages  Cell proliferation  Cell migration  Cell differentiation  Brain vesicles o Forebrain o Midbrain o Hindbrain  Early in development, the walls of the vesicles are only 2 layers thick o Ventricular zone  Lines the inside of each vesicle o Marginal zone  Lines the outside of each vesicle  Faces the pia mater  Meninge layer closest to the brain  Within these layers of telencephalic vesicle, five steps occur that give rise to all the neurons and glia of the visual cortex Five steps of cell proliferation  Step 1 o A cell in the ventricular zone extends a process that reaches upward toward the pia  Step 2 o The nucleus of the cell migrates upward from the ventricular surface toward the pial surface

o The cell’s DNA is copied  Step 3 o The nucleus, containing two complete copies of the genetic instructions, settles back to the ventricular surface  Step 4 o The cell retracts its arm from the pial surface  Step 5 o The cell divides in two o Called neural progenitors o Will give rise to all of the neurons and astrocytes of the cerebral cortex o Radial glial cells  Give rise to most of the neurons of the CNS Cell proliferation  In the beginning, there are hundreds of radial glial cells and billions of neurons  How do we get the increase? o They are multipotent stem cells o They can divide and lead to many types of cells o Expand the population of neural progenitor cells through a process called symmetrical cell division  Vast majority of neocortical neurons are born between the fifth week and the sixth month of gestation o All happening in utero  There are some, select regions in adult brain that have the capacity to generate new neurons o By and large, neuron generation mostly happens in infancy  In most parts of the brain, the neurons you are born with are all you will have in your lifetime o Many will die o Saying that only a few neurons will be new  Mature cortical cells can be classified as glia or neurons o Neurons can be further classified according to  The cortical layer in which they reside  Their dendritic morphology and axonal connections  The neurotransmitter they use  Axonic connections o Hypothetically, these different neurons can come from different precursor cell  This is NOT true  Multiple cell types, including neurons and glia can arise from the same precursor cell o Depends on what genes are transcribed during early development, cell environment, and other things o Cortical pyramidal neurons and astrocytes derive from dorsal ventricular zone, but others derive from the ventral zone Cell migration

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Many cells will climb up a process of the radial glial cell Migrate by slithering up thin processes emitted by these cells o Located in the distance between the ventricular zone and pial surface  Heading towards the surface of the brain o Immature neurons follow this path  THEN radial glial cells will take back their processes  Not all immature neurons follow this pattern o About 1/3 will travel horizontally rather than climbing up  Steps o First group of neuronal precursor (immature neuron) cells will end up in subplate layer  Subplate layer is gone by maturation o Immature cells that are destined to become the cortex start migrating  Must cross subplate  Includes neurons of layer 6  Then layer 5, 4, and so on o Cells migrate past existing layers o Layering of the cortex is assembled “inside-out” The genesis of connections  As neurons proliferate, they extend axons that have to find the appropriate target  This development of long range connections (pathway formation) in the CNS occurs in three phases o Pathway selection o Target selection o Address selection  The correct path to take depends on what cell type it is where it is located, and other complicated components  Making the decisions  pathway selection  Finding the axons and which area to innervate  target selection  Establishing retinotopy  address selection  Each step relies critically on communication of cells Communication between cells  Takes place in many forms o Direct cell–cell contact o Contact between cells and the extracellular secretions of other cells o Communication between cells over a distance via diffusible chemicals o As the pathways develop, the neurons also begin to communicate via action potentials and synaptic transmission  Dummed down o Cell-Cell o Cell-Extracellular Solution o Cell-Chemical Signaling o Cell-Synaptic Transmission

The growing axon  How does it form?  Migrated cell has found the correct layer  Neuron differentiates and extends processes that will ultimately become the axon and dendrites  At this stage, the axonal and dendritic processes are similar and are called neurites  Growing tip of neurite is the growth cone o Growth cone is what is specialized to identify the appropriate pathway for neurite elongation based on chemical communication with chemoattractants and chemorepellants Axon Guidance  Guidance Cues o Chemoattractants  Netrin  acts over distance to attract axon o Chemorepellants  Slit  Acts over distance to repulse axon  Repulsion and Attraction is largely dependent on receptors  Research on Frogs revealed that manipulation of these chemical signals could cause axons to form connections in the wrong places, affecting the frogs visual perception due to these improperly located axon connections The chemoaffinity hypothesis  The idea that chemical markers on growing axons are matched with complementary chemical markers on their targets to establish precise connections  Ephrins are a repulsive signal for temporal retinal axons Synapse Connection  When the growth cone reaches the target, the synapse is formed  Steps: o A dendritic projection touches the nearby axon o Contact leads to movement of synaptic vesicles and proteins to the presynaptic membrane o Post-synaptic receptors accumulate o Synapse begins transmitting action potentials The elimination of cells and synapses  Large scale reduction in numbers of neurons and synapses  During development, a large amount of connections and neurons are formed  However, it is important that the effective connections and neurons are strengthened and reinforced while those that are not effective are removed in a process called “pruning”  Proper brain function requires a balance of pruning and production of connections and neurons during development Cell death

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Apoptosis o Programmed cell death  After axons reach target, some presynaptic axons will die according to “death gene” that terminates the cell through apoptosis o Cell death genes  Trophic factors o Death is dependent on expression of these genes and competition amongst neurons for trophic factors that deactivate these genes o Presynaptic neurons with no target will not receive these trophic factors, causing death of the cell o Types of trphic factors  Nerve growth factor (first discovered)  BDNF  Necrosis Mechanisms of synaptic plasticity  The processes that reinforce neural connections of effective synapses  “Neurons that fire together wire together” o Neurons that produce inputs that correspond with the postsynaptic will be reinforced while those that produce irrelevant input will be cleaved o Ex: an inhibitory neuron firing with a postsynaptic neuron surrounded by excitatory neurons  “Neurons that fire out of sync lose their link” o Presynaptic neuron is active when the postsynaptic neuron is active o Synchronicity of activity corresponds to reinforcement Glutamate and Plasticity  Glutamate is the primary neurotransmitter for neurons in the cortex  Glutamate acts on special receptors like NMDA and AMPA  NMDA receptors are both voltage gated and ligand gated meaning that a variety of conditions must be met for them to open  To achieve significant release of calcium, the NMDA receptors must open as well as other receptors NMDA RECEPTORS  Activation of the NMDA receptor demonstrates effective synaptic activity and the neuron will trigger changes to facilitate reinforcement of the connection o Ex: insertion of receptors and myelination  This is the process of Long Term Potentiation where downstream changes also occur to make the firing more effective...