Foundations of Neuroscience Notes week 13

Foundations of Neuroscience I: Neurogenesis and Cell Development

• Neurons and Microglia:

  • Neurons communicate and process information, while microglia defend against infections.

Roadmap for Week 13

• Focus Areas:

  • Neuroplasticity: Neurogenesis, cell migration, differentiation, synapse formation, and pruning.

  • Activity and experience-dependent wiring, LTP (Long-Term Potentiation), and LTD (Long-Term Depression).

Key Concepts in Neurogenesis

• Neurogenesis involves:

  • Cell proliferation (expansion of neural stem cells).

  • Cell migration to their final destination.

  • Differentiation into specific cell types (neurons, astrocytes, etc.).

  • Formation of axonal connections and synapses.

Neurogenesis Mechanism

• Stem Cells:

  • Radial glial cells differentiate into neurons and glial cells.

  • Early progenitor cells are capable of further differentiation.

• Neurogenesis Process:

  1. Cells in the ventricular zone extend processes to the pial surface.

  2. They migrate along these processes as DNA replication occurs.

  3. Following migration and division, cells become post-mitotic, and their fate is determined by the cleavage plane (horizontal vs. vertical).

• Importance of Notch-1 and Numb:

  • Notch-1 promotes differentiation into a postmitotic neuron when unopposed by Numb, which suppresses it.

Development of Brain Structures

• Neural Tube Development:

  • Precursors for the CNS forms the brain and spinal cord.

  • Dorsal area becomes pyramidal neurons; ventral area gives rise to inhibitory interneurons.

• Cell Migration:

  • Cells move along radial glial fibers to reach their appropriate cortical positions, developing layers in the cortex from the deep layers outward.

Synapse Formation

• Motor Neuron Example:

  • Neuromuscular Junction (NMJ):

  • ACh (acetylcholine) released by motor neurons binds to ACh receptors, leading to muscle depolarization and contraction.

  • Agrin plays a crucial role in clustering ACh receptors at the NMJ through interactions with MuSK (muscle-specific kinase).

• General Steps in CNS Synapse Formation:

  1. Dendritic filopodium contacts an axon.

  2. Synaptic vesicles move to the presynaptic membrane.

  3. Neurotransmitter receptors collect at the postsynaptic membrane.

Neural Circuit Pruning

• Pruning involves the reduction of excess neurons and synapses following initial development.

  • Apoptosis: Regulated cell death ensures proper neural circuit formation.

  • Trophic Factors:

  • Factors like BDNF (brain-derived neurotrophic factor) influence cell survival and growth, preventing unwanted apoptosis.

• NMJ Example in Pruning:

  • Lack of muscle activity can lead to the internalization of ACh receptors and loss of synaptic connections.

Activity and Experience-Dependent Wiring

• Development is influenced by neural activity and experience, exemplified by critical periods for sensory input shaping synaptic connections.

• Hebbian Plasticity:

  • Cells that fire together wire together (correlation strengthens connections).

• Influences of Visual Input:

  • Ocular dominance columns in the visual cortex can be altered by visual experience, particularly during sensitive periods.

Long-Term Potentiation (LTP) and Depression (LTD)

• LTP Mechanism:

  • Strong NMDA receptor activation leads to increased AMPA receptor insertion into the synapse, strengthening synaptic transmission.

• LTD Mechanism:

  • Low levels of NMDA activation result in the removal of AMPA receptors, weakening synaptic connections.

Summary

• Understanding the stages of neurogenesis, cell migration, synapse formation, and the mechanisms of plasticity is vital in neuroscience to comprehend brain development and function.