Plasticity

Neuron Survival and Neurotrophic Factors

  • Understanding the role of neuron survival, synapse pruning, and maintenance dependent on neurotrophic factors and synaptic activity.

  • Importance of neurotrophic factors for neuron survival during development and their regulatory effects on interconnected neurons.

Development and Experience-Dependent Plasticity

  • Example of experience-dependent plasticity during development:

    • Certain types of neuronal connections depend on experience (e.g., sensory inputs).

    • Impact of brain damage: post-injury experiences can lead to the reorganization of neural connections and recovery.

Neurogenesis Across Species

  • Locations and occurrences of neurogenesis:

    • Amphibians: Neurogenesis occurs in the brain and spinal cord through various life stages.

    • Birds: Neurogenesis often takes place in specific brain regions such as the hippocampus.

    • Mammals: Notable neurogenesis in the hippocampus and olfactory bulb, with evidence of neurogenesis in humans through techniques like 14C incorporation.

Target-Derived Trophic Support

  • Target-derived trophic support regulates the survival of connected neurons:

    • The number of surviving motor neurons depends on the amount and type of target (muscle fibers).

Elimination of Neurons and Synapses

  • Definition:

    • Large-scale reduction of neurons and synapses that occurs during development.

  • Example:

    • Extra motor neurons produced in spinal cord undergo apoptosis, a form of programmed cell death crucial for refinement of neural circuits.

  • Advantages of apoptosis:

    • Helps fine-tune neural networks by eliminating excess cells.

  • Importance of trophic factors:

    • Essential for survival (e.g., Nerve Growth Factor).

Synapse Pruning

  • Definition and significance of synapse pruning:

    • Process where excess synaptic connections are eliminated to enhance the efficiency of active synapses.

  • Example of synapse pruning:

    • Initial polyneuronal innervation of muscle fibers reduces to single innervation as the organism matures.

Neurotrophins and Their Functions

  • Neurotrophins: A class of proteins that influence the growth, survival, and differentiation of neurons.

    • Discovery noted by Levi-Montalcini & Cohen; key neurotrophins include NT4/5 and BDNF (Brain-Derived Neurotrophic Factor).

    • Regulate functions such as:

    1. Neuronal survival.

    2. Neuritic growth.

    3. Synaptic strength.

  • Neurotrophin release is influenced by synaptic activity; increased activity leads to enhanced neurotrophin release.

Changes in Synaptic Capacity

  • Synapse elimination at the neuromuscular junction: Initially multiple motor neurons innervate a single muscle fiber, which retracts to a single neuron following development.

    • How many muscle fibers does one alpha motor neuron innervate?

    • Many (exact number varies).

    • How many alpha motor neurons innervate a single muscle fiber?

    • One.

  • This concept parallels the formation of ocular dominance columns in the primary visual cortex, showcasing similar pruning mechanisms.

Developmental Changes in Synaptic Capacity

  • Significant changes occur during postnatal life in the human brain:

    • Particularly in regions such as the primary visual cortex (V1) and prefrontal cortex.

    • Synaptogenesis followed by pruning, with pruning being activity-dependent, peaking in prefrontal cortex.

  • Illustration of increased myelination alongside these synaptic changes.

Examples of Motor Neuron Outcomes Based on Neurotrophic Signaling

  • Scenario example:

    • If a motor neuron innervates nine muscle fibers and only three receive substantial NT-4/5 signaling:

    • a. Neuron dies if receiving neurotrophins at less than half its synapses (false).

    • b. The neuron survives with all synapses retained (false).

    • c. Synapses on the fiber with the most NT-4/5 are retained (not necessarily true).

    • d. Correct: The neuron will likely lose the synapses on the six muscle fibers where it is receiving minimal neurotrophic support, while synapses on the other three muscle fibers will remain due to adequate neurotrophic signaling.

Synapse Strengthening and Elimination During Development

  • Examples include:

    • Transition from polyneural innervation to single innervation in various systems (e.g., motor neurons/muscle fibers, ocular dominance in V1, specific ganglia).

  • Mechanisms driving synapse strengthening or elimination:

    1. Activity dependence: Neurons that fire together strengthen their synaptic connection (Hebb’s postulate).

    2. Competition for neurotrophins: Only the most active synapses retain supportive neurotrophins (e.g., NGF, BDNF, NT-3).

Brain Plasticity

  • Brain plasticity and synapse pruning continue beyond infancy:

    • Dr. Giedd's observations indicate gray matter thickening prepuberty due to neuroanatomical changes (suggest chromatolysis rather than pure cell proliferation as a hypothesis for this effect).

    • Dendritic and axonal changes contribute to increased synaptic connections rather than a higher number of neurons.

Nervous System Recovery Post-Injury

Peripheral Nervous System (PNS) Regeneration

  • Recovery processes in PNS involve:

    • Axonal regrowth that mirrors developmental processes, enabling neurons to navigate and reconnect appropriately.

  • Questioning whether it's possible to repair the CNS following injury.

    • Potential for neuron replacement and recovery from trauma (e.g., spinal cord injury, degenerative diseases).

Neurogenesis Sources in Adult Mammals

  • Notable sites of neurogenesis:

    • Olfactory bulb and hippocampus show significant generation of new neurons.

    • New neurons primarily become local interneurons rather than long-projecting neurons.

Regulation of Neurogenesis

  • Factors increasing neurogenesis:

    • Exercise boosts neurogenesis.

    • Brain injury can stimulate neurogenesis as a repair mechanism.

    • Learning and enriched environments promote neuron formation.

    • Antidepressants (SSRIs) can lead to increased neurogenesis over time (2-week delay in effectiveness).

  • Factors decreasing neurogenesis:

    • Chronic stress and aging can inhibit the formation of new neurons.

Mechanism of Regeneration in the Peripheral Nervous System

  • Key factors promoting regeneration include:

    • The response from Schwann cells and macrophages remove debris and support axon regrowth via growth factors and extracellular matrix.

  • The regeneration process is location-dependent; axonal injury generally allows for regeneration if proximal of the cell body but limited in CNS due to glial proliferation restraint.

Case Study: Regeneration in Humans

  • Historical example:

    • Recovery case involving John Stennes, severed arms reattached successfully by Dr. Allen Van Beek, illustrating potential of surgical intervention in enhancing nerve recovery.

Peripheral Nerve Regeneration Experiment

  • Henry Head's study documented areas of regained sensation after 2-6 months:

    • Differentiation in recovery of sensitivity to pin prick and light touch illustrated the complexities of axonal regrowth to their specific targets.