Neuroscience Exploring the Brain Chapter 22

1. The occurrence of neurons

cell proliferation cell migration cell differentiation

Cell Proliferation,

       The brain develops from five small fluid-filled vesicle walls, and these fluid-filled spaces remain in the adult brain to form the ventricular system. In the early stages of development, the vesicle wall has only two layers: the chamber layer and the marginal layer. The chamber layer is located inside each vesicle, while the marginal layer is closer to the pial side. Telencephalic vesicles give rise to all the neurons and glial cells of the visual cortex through a "ballet of cells."

• process:
• (1) The process of a cell in the ventricular layer extends upward to the pia mater.
• (2) The nucleus of the cell migrates from the ventricular side to the pial side, and the cell DNA is replicated at the same time.
• (3) The nucleus containing the duplicated genetic material returns to the ventricular side.
• (4) Cell processes retract from the pial side.
• (5) The cell divides into two daughter cells

Cell division: vertical division and horizontal division
       . After vertical division, the two daughter cells continue to divide in the chamber layer, expanding the number of neuronal precursor cells in the early stages of development. Later in development, horizontal division dominates. At this time, the daughter cells farthest from the ventricle begin to migrate outward, reach the cerebral cortex and occupy a certain position, and then lose their ability to divide. The remaining daughter cells remain in the chamber layer and continue to divide. Ventricular precursor cells repeat this pattern until all cortical neurons are generated.
       In humans, the vast majority of neocortical neurons are generated between the fifth week and fifth month of embryonic life.

1. Cell fate determination (plane of division)

   • The differences between cells are determined by specific genes that produce specific messenger RNA (mRNA) and ultimately specific proteins. Thus, cell fate is differentially regulated by gene expression during development, which is regulated by cellular proteins, namely transcription factors.
   • Transcription factors are unevenly distributed in the same cell, and the division plane can determine the distribution destination of the factors.
   • Example: The proteins notch-1 and numb migrate to the two poles of the chamber layer precursor cells respectively. When the cell divides vertically, notch01 and numb are symmetrically allocated to the two daughter cells. When the cell divides horizontally, notch-1 is allocated to migrate away. Among the daughter cells, number is listed in the daughter cells that continue to divide.

2. mature cortical cells

   • Glial cells, neurons (can be further classified based on cortical location, dendritic morphology, and neurotransmitters)
   • Neural stem cells: precursor cells with the potential to generate different types of tissues

3. The final fate of migrating daughter cells

   • Multiple factors: Age of precursor cells and environment when they divide
   • The first cells to migrate from the ventricular layer form the subcortical plate
   • As development progresses, the subcortical plate eventually disappears completely, and subsequently dividing cells form neurons from higher to lower layers.

cell migration

1. cell migration
   • Sliding migration of thin fibers radiating from the ventricular layer to the leptomeninges
   • Fibers come from special radial glial cells
   • Immature neurons, called neuroblasts , migrate along these radiating pathways from the ventricular layer to the brain surface.
   • When cortical organization is complete, radial glia retract their radial processes.
   • Not all cells migrate along the paths provided by radial glia, and approximately one-third of neuroblasts migrate horizontally into the cortex.

Cell Differentiation

1. Cell Differentiation

   • Concept: The process by which cells take on neuronal phenotypes and characteristics as a result of a specific spatiotemporal pattern of gene expression
   • The onset of neuroblast differentiation is marked by the uneven distribution of cellular components from precursor cells. When neuroblasts reach the cortical plate, further differentiation begins. Thus, layer VI and V neurons have already differentiated into identifiable pyramidal cells before layer II cells reach the cortical plate.
   • A sign that neuroblasts differentiate into neurons: when neurites grow on the cell body.
   • The complexity of dendrites is not completely preprogrammed, and the fine structure of axons and dendrites also depends on the influence of "environmental" factors in the cortex.

2. Differentiation of cortical areas

   • neocortex
   • Cortical neurons originate in the ventricular layer, migrate along radial glial cells, and occupy their final position in a certain layer of the cortex.
   • Cortical areas differ not only in their cellular architecture but also in their interconnections, particularly with the dorsal thalamus.
   • The thalamus is important for the specialization of various cortical areas
   • The reason why thalamic axons happen to reach and stay under the parietal cortex: Subcortical plate neurons that follow a radial migration pattern attract thalamic axons to reach different parts of the cortex during development: LGN axons to the occipital lobe, VP Nuclear axon to parietal lobe
   • When the overlying cortical plate is large enough, axons invade the cortex. Arrival of thalamic axons initiates cellular differentiation in the adult brain.

2. The occurrence of cell connection

1. In the development of the central nervous system, long-distance connections or pathway structures are divided into three stages: path selection, target selection, and address selection.
   • Pathway selection: Axons must choose the correct path.
   • Target selection: Axons must select the correct structures to innervate.
   • Address selection: The axon must select the correct cell to make a synaptic connection with the target structure.
2. Axon growth
   • Neurite: The dendrites and axons where neurons begin to differentiate. The growing tips of neurites are called growth cones.
   • Growth cones: Identifying suitable pathways for neurite outgrowths.
   • Growth cone leading edge: Made of flat membranes called lamellipodia.
   • Filopodia: Spicules emerging from the depths of lamellipodia. Used to explore the surrounding environment and enter and exit lamellipodia at will. When filopodia extend and grasp the substrate, they pull the growth cone forward.
   • Growth: Axons grow only when the growth cone extends along the substrate surface. The substrate consists of fibrin, a protein deposited in the extracellular matrix . Growth can only occur when the appropriate proteins are present in the extracellular matrix. Example: The interaction between laminin and integrins (growing axons express a special surface molecule that is linked to laminin) promotes axon extension.
   • Fasciculation: The mechanism that causes axons to stick together and grow together. Nerve fiber fasciculation is caused by the expression of specific surface molecules called cell adhesion molecules (CAM). CAMs in adjacent axonal membranes are tightly connected to each other, allowing axons to grow together.
3. axon guidance
   • A general pattern of pathway formation: Connections are established by leading axons, which stretch as the nervous system expands and guide later-developing neighboring axons to the same target site.
   • Guidance signals: Growth cones can be distinguished based on the different molecules expressed on their membranes. The interaction of these cell surface molecules with guidance signals in the environment determines the direction and amount of axonal growth. The signal can be attractive or repulsive, depending on the receptors the axon carries.
   • Chemoattractant: A diffusible molecule that acts over long distances to attract axons to grow toward their target site.
   • Chemical resistance factors: can drive axons away.
   • Create a domain map
4. synapse formation
   • Mechanism: Synapses can be formed after growth cones come into contact with their target sites.
   • Example: At the neuromuscular junction, the first step is to induce a cluster of postsynaptic receptors at the contact site. The interaction between growth cone-secreted proteins and the target cell membrane initiates this swarming response. in secreted proteins.
   • • 1. A protein called agrin is deposited in the extracellular space at the contact site, and the formed protein becomes the basal layer.
   • • 2. argin interacts with MuSK (muscle-specific kinase) in the muscle cell membrane , and this interaction is activated by rapsyn.
   • • 3. Through the above effects, ACh (acetylcholine) receptors cluster in the postsynaptic membrane. At the same time, the number of this group of receptors is regulated by another molecule released by axons, namely neuregulin, which can stimulate the expression of receptor genes in muscle cells.
   • The interaction between axons and targets is bidirectional.

3. Death of cells and synapses

1. Cell death: The overall number of neurons decreases during pathway formation. This process is programmed apoptosis. After the axon reaches the target site, synapses begin to form, and the number of presynaptic axons and neurons gradually decreases.
2. Nerve growth factor: polypeptide, NFG (nerve growth factor), produced by target tissues of sympathetic axons in the autonomic nervous system.
3. Neurotrophic factor: NGF is a member of this large family, including proteins NT-3, NT-4 and brain-derived neurotrophic factor (BDNF). It has specific receptors on the cell surface. Most of the receptors are nerve cells. Nutritionally inactive protein kinase (trk receptor)
4. Changes in synaptic capacity: Each neuron can receive a limited number of synapses on its dendrites and cell body (synaptic capacity), which peaks early in development and continues to decrease as the neuron matures.

4. Activity-dependent synaptic rearrangement

1. Synaptic rearrangement: Changing synapses from one way to another.
   • Synaptic rearrangement is the final step in the address selection process.
   • Synaptic rearrangements are the result of neuronal activity and synaptic transmission.
2. synapse separation
   • Dissociation of retinal axons in LGN
   • Dissociation of LGN input information in striate cortex
3. synaptic convergence
4. synaptic competition
5. modulating influence

5. Basic mechanisms of cortical synaptic plasticity

1. Mechanisms and rules:
   • Synapse formation does not require any electrical activity, and activation of synaptic transmission during development plays a key role in the final refinement of connections.
   • law:
     • (1) Neurons that are activated together are connected together.
     • (2) Neurons that activate out of sync will lose their connections.
2. Transmission at excitatory synapses in the immature visual system
   • Glutamate: Neurotransmitter that modifies synapses. Can activate several postsynaptic receptor subtypes.
   • Neurotransmitters: G protein-coupled receptors and transmitter-gated ion channels.
   • Postsynaptic glutamate-gated ion channels allow positively charged ions to enter the postsynaptic cell and can be further classified as AMPA receptors or NMDA receptors.
   • AMPA receptors and NMDA receptors are co-distributed at many synapses.
   • NMDA receptor: Due to the action of magnesium ions at the channel, the NMDA receptor becomes a voltage-gated channel. At resting membrane potential, due to the movement of magnesium ions into the channel, the inward current flowing through the NMDA receptor is blocked. However, by depolarizing the locked membrane potential, the magnesium ions are removed and current flows freely into the cell. Therefore, only when glutamate is released from the presynaptic terminal and depolarization occurs in the postsynaptic membrane, a large amount of current can pass through the NMDA receptor. Another feature: its channel can mediate calcium ion influx, and the amplitude of calcium ion influx in the NMDA receptor channel provides a specific signal for the level of pre-synaptic and post-synaptic mutual activation.
3. long-term potentiation of synaptic transmission
   • Strong excitation of NMDA receptors enhances outstanding transmission efficiency, a phenomenon called long-term potentiation. (LTP) AMPAylation of synapses leads to enhanced synaptic transmission. AMPA is acquired during development.
4. synaptic long-term depression
   • Low levels of NMDA receptor activity and low calcium ion influx, and reduced AMPA receptors.
5. end of critical period hypothesis
   • (1) Plasticity decreases when axonal growth ceases.
   • (2) Plasticity decreases as synaptic transmission matures.
   • (3) Plasticity decreases when cortical excitation is restricted.

Review questions

answer:

1. Cortical neurons arise in the ventricular layer, migrate along radial glia, and occupy their final position in a certain layer of the cortex. Migration first crosses the cortex to form the cortical plate, and then cells that reach the cortical plate will differentiate into layers VI to I.
   2. Path selection, target location selection, address selection? ? ? ? ? ??
   3.? ? ? ?
   4. Weakening of polyinnervation of muscle fibers: changes in synaptic capacity. Initially each muscle fiber can receive input from several motor neurons, but eventually this multi-innervation disappears and each muscle fiber only receives synaptic input from a single alpha motor neuron.
   Separation of retinal terminals in the LGN: The first axons to reach the LGN usually originate from the contralateral retina, and those axons extend out and occupy the entire pattern. Later arriving ipsilateral axons are mixed with contralateral axons. Axons from both eyes then separate from each other and enter eye-specific areas.
   Similar, develop first and then separate.
   Different: Enter different functions? ? ? ?

5. If early treatment is not carried out, the permanent loss of stereoscopic vision will occur after the critical period is over. Strabismus makes the separation of visual dominance columns in the fourth striate cortex more pronounced.
6. The critical period ends.
- (1) Plasticity decreases when axonal growth ceases.
- (2) Plasticity decreases as synaptic transmission matures.
- (3) Plasticity decreases when cortical excitation is restricted.