NSB CORE 1:Wiring the Visual System

Nature vs. Nurture: Exploration of the contributions of genetics (nature) and environmental experiences (nurture) to the wiring of the nervous system.
- Key Questions:
- How do the relative contributions of nature and nurture differ across various parts of the nervous system?
- How do these contributions vary at different stages of development?
- Are there differences amongst various animal species?
Focus: The mechanisms involved in the development of the nervous system with a specific emphasis on wiring.

Chemoaffinity Hypothesis: A foundational theory proposing that cells and fibers possess unique chemical markers that direct their growth and connections.
- Molecular Gradients: Differences in the concentration of certain molecules guide axon growth.
- Axon-Axon Competition: Interaction between axons that influences their targeting decisions.
- Activity-Dependent Wiring: Wiring adjusted by neuronal activity and experiences.
- Monocular Deprivation and Critical Period: The significance of specific developmental timeframes in visual inputs affecting cortical development.
- Spontaneous Activity: Retinal Waves: The role of spontaneous neuronal activity preceding vision in creating wiring patterns.
- Hebb’s Rule: A principle stating that connections strengthen when a presynaptic neuron repeatedly activates a postsynaptic neuron, linked with NMDA receptor activity.

Pathfinding and Target Selection: RGC (Retinal Ganglion Cells) axons must navigate a series of critical choices to ensure proper wiring:
- Exiting the Eye: Axons must leave the retina efficiently.
- Crossing the Midline: Axons encounter the optic chiasm where some cross to the opposite side.
- Target Identification: Axons must locate specific brain targets (e.g., LGN and SC).
- Retinotopic Positioning: Correct endpoints must be achieved for proper visual mapping.
- Synapse Formation: Synapses must be formed accurately with the right partners.

Predetermination vs. Functional Selection: Historically proposed theories about how axons determine targets.
- Sperry’s Optic Nerve Regeneration Experiment (Newts): Aiming to distinguish between preselection and functional selection based on the outcome of vision restoration during regeneration.
Results of Sperry’s Experiment: Observed inverted vision post-regeneration, leading to conclusions on the predetermined nature of RGC axons in maintaining positional information despite altered visual input.
Point-to-Point Connections: The orderly projections of regenerating retinal axons emphasize the importance of precise axon targeting.

Identification Tags: The premise that axons and target cells catalog chemical tags that facilitate selective attraction and bonding.
- Specific Molecular Differences:
1. Between cells in various tectum regions.
2. Within RGCs originating from different retinal areas.

Repulsion vs. Attraction: Temporal RGC axons exhibit repulsion from the posterior tectal membrane via specific chemical interactions, leading to critical investigations into the underlying protein mechanisms, specifically ephrins and Eph receptors.
Experimental Setup: Utilization of stripe assays to understand retinal axon interaction with tectum membranes and the underlying biochemical signals.
Relative Eph Expression Levels: The targeting positions of RGC axons are modulated by relative levels of Eph expression, as shown in experiments with mouse knock-ins overexpressing EphA3.

Binding of Tectal Ephrin-A5 and Retinal EphA3: Integral to understanding how these interactions lead to axon repulsion and competition in targeting.
Complexity of Targeting Signals: A growing understanding of the multiple signaling methodologies beyond mere gradients, such as counter gradients and multifaceted signaling systems like bidirectional signaling of Eph/ephrin pairs.

Role of Ocular Dominance Columns: Eye-specific columns form in V1, with the evidence of monocular deprivation showcasing significant developmental impacts on visual experience.
Impact of Monocular Deprivation: Causing shifts towards the ipsilateral eye and emphasizing the importance of competitive inputs for the setup of ocular dominance.
Critical Periods: Defined crucial developmental timeframe ranges (e.g., 4th-12th weeks in cats) which determine visual cortex organization and plasticity.

Prenatal Wiring in Monkeys: Ocular dominance columns begin forming even before eyes are open, suggesting an intrinsic timeline for structure generation.
Spontaneous Retinal Waves: Pre-visual input waves of activity that organize neuronal wiring before functional vision, revealed through Ca2+ imaging and multielectrode arrays.
Role of Retinal Waves: In promoting eye-specific segregation of retinal ganglion cells is crucial for establishing organized visual pathways.

Hebb's Rule Revisited: Highlights how consistent presynaptic activity strengthens synapses through correlated firing.
Hebbian Plasticity in Retinal Connections: This adaptive process is essential for the segregation and developmental maturation of RGC connections with LGN neurons.
NMDA Receptors: Operate as molecular coincidence detectors, requiring simultaneous presynaptic glutamate release and postsynaptic depolarization for activation.
Consequences of Correlated Firing: Over time, there is a prompt for synaptic strengthening and dendritic growth, enabling further development of neural connections.

Cooperation of Molecular Determinants and Neuronal Activity: Molecular guides initially direct axons, while neuronal activity assists in refining their organization and features.
Nicotinic Acetylcholine Receptor Subunits: Their roles in retinal wave propagation indicate a coordinated mechanism between molecular signals and functional outcomes in visual system development.