Synapses

Definition of Growth Cone: The growth cone is the dynamic, motile tip of a developing axon or dendrite. It is crucial for sensing the environment and directing cellular movement towards synaptic targets.
Growth Cone Navigation: Refers to the mechanisms by which growth cones find their paths to target areas. This navigation involves interaction with various guidance cues present in the extracellular environment.

General Categories of Guidance Cues:
- Attractive Cues: These guide neurons toward specific targets.
- Repulsive Cues: These prevent axons from growing toward particular areas.
Examples and Effects:
- Netrins: Attract axons across the midline.
- Ephrins and Eph receptors: Inhibit axon growth when bound, modulating navigation based on their gradient.

Presynaptic Axon Growth: Axons extend towards their target cells.
Selective Adhesion: Involves adhesion molecules like cadherins which play a role in binding similar isoforms between pre- and postsynaptic cells.
Synaptic Protein Recruitment: Involves synaptic vesicles and proteins aggregating in presynaptic terminals, while postsynaptic terminals cluster receptors.
Bidirectional Signaling: Communication occurs between pre- and postsynaptic cells for synapse stabilization.

Autism and Synapse Formation: The symptoms of autism spectrum disorders (ASD) have been correlated with genes responsible for synapse formation. These include neurexins and neuroligins that are involved in synapse adhesion.

Formation of Neural Tube: The process begins with the formation of the neural tube, crucial for central nervous system development.
Neurogenesis: Characterized by cell division and differentiation, leading to an increased number of neurons and glial cells (gliogenesis).
Cell Migration: Neurons migrate to their appropriate locations.
Formation of Connections: Includes axon pathfinding and synaptogenesis, ensuring proper neuron communication.

Alcohol's Impact on Neural Development:
- L1 mutations are known to cause neurological disorders, particularly impacting conditions like corpus callosum agenesis and mental retardation, mirroring the effects observed in Fetal Alcohol Syndrome.
- Hypothesis on Similarities: Ethanol may inhibit L1 adhesion, leading to similar developmental issues.

Retinal Axons Navigation: Understanding the differential behavior of nasal vs. temporal retinal ganglion cells in crossing the optic chiasm.
- Transcription Factor Zic2: Exclusive to temporal retina, activates EphB1, inhibiting axon growth when bound to ephrins, preventing temporal axons from crossing.

Experiment involving the rotation of the eye in newts/frogs showed that axons return to their original targets despite the altered position of the eye.
- Conclusions: The existence of a topographic map that governs axon guidance.

EphA Receptor Gradient: The spatial distribution of EphA receptors and their inhibitory interaction with ephrins across the tectum is essential for axon targeting.

Key Mutations: L1 and ROBO mutations lead to a diminished corticospinal tract and corpus callosum.

Selective Retention and Pruning: Regulated by neuronal activity and neurotrophic factors.
- Factors such as neuregulin in the brain and agrin in motor neurons are crucial in clustering receptors.

Diagnosis and Symptoms: Features poor communication, repetitive behaviors, and broad descriptive criteria.
Genetic Factors: ASD has a significant heritable nature, with most implicated genes involved in synapse adhesion.
- High incidence (1 in 150). Trends suggest an increase in diagnoses rather than actual prevalence.
- Misconceptions about vaccines and medication during pregnancies clarified with evidence.
Commonalities in Affected Genes: Most relate to synapse development and function.