LIN350C 19 Neuroplasticity

Overview: The brain develops more cells than necessary during development.
Key Figure: Rita Levi-Montalcini; recognized for her work on nerve growth.
Guidance: Cellular growth is orchestrated through feedback signals derived from target tissues.
Example: Snake venom has been shown to enhance nerve fiber outgrowth in laboratory Petri dishes; this effect is attributed to a substance known as Nerve Growth Factor (NGF).

Concept: Nerve cells initially proliferate beyond required amounts but must compete for a limited supply of neurotrophic factors like NGF.
Mechanisms:
- Caspase Proteins: These proteins facilitate programmed cell death (apoptosis) by breaking down cells from within.
- Microglia: A type of supportive glial cell responsible for clearing cellular debris following cell death.

Process: In the developing brain, immature neurons exhibit ‘promiscuity’ by forming an excessive number of synaptic connections, which are later trimmed back to eliminate excess, mismatched, and redundant synapses.
Timeline:
  - Synapse formation initiates during embryonic development and continues in the early postnatal stage.
  - Functional synapses start appearing in humans as early as 23 weeks of gestation.
  - Peak synaptic density reaches between 2.5 to 8 months of age, while certain regions of the frontal cortex continue to generate new synapses into the third year of life.

Concept: The human brain achieves its full size by around 16 years of age, but mature functionality, especially in the prefrontal cortex, is only reached once the pruning process concludes.
Behavioral Correlation: Gradual brain modifications related to pruning also correlate with behavioral changes observed during development.
Metaphor by Michelangelo: “The sculpture is already complete within the marble block, before I start my work. It is already there, I just have to chisel away the superfluous material.”

Function: The frontal cortex is crucial for complex cognitive functions such as decision-making and assessing rewards.
Adolescents: Due to the protracted maturation period of the frontal cortex, adolescents often display risk-taking behaviors driven by the need for peer approval.
Outcome of Synaptic Pruning: As synaptic pruning progresses into the second and third decades of life, executive functions improve, resulting in more responsible adult behavior.

Research by David Hubel and Torsten Wiesel (1960s):
  - They discovered that inputs from the left and right eyes converge in the primary visual cortex and compete for neural space, an interplay determined by visual experience.
  - An experiment involved suturing one eyelid of newborn kittens, revealing that this manipulation had a significant detrimental effect on the visual cortex’s development.
  - Reversibility: Despite the adverse impact, symptoms were reversible if the eyelid was reopened before a certain age threshold was reached.

Neuronal Maturation:
  - Maturation of inhibitory interneurons is essential for developing the visual cortex. Key components include:
    - GABA: A neurotransmitter critical for inhibitory signaling.
    - Basket Cells: A type of GABAergic interneuron.
    - OTx2 Proteins: Proteins that prompt the maturation of basket cells.
    - Perineural Nets (PNNs): Extracellular matrices surrounding neurons that are significant for synaptic stabilization.
Evidence:
- Brain-derived neurotrophic factor (BDNF) has been shown to enhance learning and cognitive development.
- Disruption of PNNs can extend the critical period for visual cortex development.

Researcher: Paul Bach-y-Rita
Reference: https://psychology.stackexchange.com/questions/9135/why-is-sensory-substitution-not-that-successful

Learning Mechanism: Blind individuals can navigate using echolocation, generating clicking sounds with their tongues or feet that help them interpret the surrounding environment based on the returning echoes.
Training: Mastery of echolocation necessitates extensive training, and proficient practitioners can accomplish intricate tasks typically unmanageable without sight, such as playing video games or riding bicycles.
Neuroplasticity Impact: During echolocation, the auditory information is processed in the visual areas of the brain rather than the auditory regions.

Plastic Changes in Deaf Individuals:
- In people born deaf, the auditory cortex, typically responsible for processing sound, becomes activated in response to visual stimuli.
- It has been observed that deaf individuals may possess enhanced peripheral vision.

Donald Hebb's Principles: - “Repetition of activity tends to induce lasting cellular changes that add to its stability.”
- “When an axon of cell A is sufficiently close to excite cell B and repeatedly or persistently participates in firing it, metabolic changes or growth processes occur in one or both cells, increasing A’s firing efficiency with respect to cell B.”

Research by Bliss and Lømo: Their studies demonstrated that stimulating neuronal fibers at a frequency of 10 to 20 Hertz resulted in a significant enhancement of the electrical responses recorded in the hippocampus.
Characteristics of Responses:
- Responses were not only larger but also sustained for more extended periods, indicating slower returns to baseline activity.

Definition: N-methyl-D-aspartate (NMDA) receptors function as ion channels that allow the passage of sodium, potassium, and calcium ions, but their central pore is blocked by a magnesium ion under resting conditions.
Mechanism Inducing LTP: Under high-frequency stimulation, glutamate release increases, leading to the removal of magnesium blockage, permitting ionic currents to flow through the NMDA channel.

Contribution: Astrocytes establish networks both amongst themselves and with neighboring neurons; their activity persists over seconds compared to neurotransmission, which occurs within milliseconds.
Function of Glutamate: When astrocytes release glutamate, they can excite entire clusters of neurons, promoting synchronization within neuron populations.
Impact on LTP: The ongoing activity of astrocytes may also facilitate long-term potentiation by persistently activating postsynaptic membranes in synchrony with incoming signals.

Ongoing Process: Synapses within the adult brain are generally in a state of elimination, which appears to be managed by microglia.
Monitoring Mechanism: Microglia continuously survey their local brain regions and selectively engage with stubby spines, the least stable of synaptic connections.
Function of Microglia: They effectively monitor synapse status in their vicinity and engulf the less persistent unwanted synapses.

Prenatal Phase:
- Neuronal proliferation
- Cellular suicide
Pre- and Postnatal Phase:
- Presynaptic proliferation
- Presynaptic pruning
Predominantly Postnatal (Adult Brain):
- Long-term potentiation
- Postsynaptic pruning