Unit 4, Chapter 23 covers brain wiring, including:
Genesis of neurons
Genesis of connections
Elimination of neurons and connections
Key question: How does the most complicated tissue reliably build itself from nothing?
Peak brain growth occurs prenatally; white matter (connections) increases for a bit longer, but grey matter (neurons) number does not.
Mature brain characteristics:
Many types of neurons.
Neurons wired together in a specific way.
Connections that allow the brain to make sense of the world.
To create a functioning brain from nothing, we need to:
Generate many types of neurons.
Connect them appropriately.
Adjust the connections to match experience.
Most neurons and connections are generated before birth; peak neurogenesis in humans sees 250,000 neurons born every minute.
Very few neurons, if any, are generated in the adult brain (adult neurogenesis).
Genesis of Neurons
Neurons and glia come in many different types.
All neurons and glia arise from neural stem cells (neural progenitor cells).
Neural stem cells are located in the periventricular region.
Different cell types arise from:
Inequitable division at the time of cell splitting.
Local environment: chemoattractants & chemorepellants.
Symmetrical division (vertical cleavage):
Daughter cells both remain in the ventricular zone and continue to divide and proliferate.
Asymmetrical division (horizontal cleavage):
Two daughter cells have different fates; one cell migrates away to its final position within the cortex and stops dividing; the other cell remains in the ventricular zone and continues to divide.
This involves unequal vs. equal sharing of cellular components.
Differentiation of neurons depends upon chemoattractants and chemorepellents.
Example: Pyramidal cells all have the same orientation because Semaphorin 3A is a chemoattractant for their dendrites and a chemorepellent for their axons, causing them to polarize.
Genesis of Cortex
The cortex is built one layer at a time, inside out.
Stem cells (precursor cells) live in the periventricular zone and migrate from there.
Precursor cells give rise to different types of cortical neurons in a specific sequence:
Subplate neurons (disappear later)
Neurons of cortical layer VI, V, IV, III, II (in this order)
The cortex is assembled "inside out."
Neuroblasts (immature neurons) migrate along processes of radial glial cells.
The first neuroblasts form the subplate, then subsequent waves of neuroblasts migrate past the subplate to form the cortical plate.
Subsequent waves of neuroblasts produce the cortical layers, inside out.
Neurogenesis in Adults
The old dogma: "There is no adult neurogenesis."
New neurons can be generated in the adult brain, apparently yes in rodents (but less clear in humans).
Where it occurs:
Hippocampus (memory)
Olfactory bulb (smell).
Stimulating cell proliferation in the adult rat hippocampus is important for learning, memory, and emotional health.
Neurogenesis can be stimulated with environment enrichment, exercise, and socialization.
Most new neurons won’t survive; their function is not known and is the focus of active research.
Genesis of Neurons Summary
Neurogenesis is the process of making new neurons.
Neural stem cells create all types of neurons.
Neurogenesis occurs in the periventricular region.
Most (>99.99%) of your brain’s neurons were ‘born’ before you were.
Neuron types come from inequitable division of stem cells and influences of chemicals on baby neurons.
Symmetric / vertical cleavage creates more stem cells and occurs most early in development; asymmetric / horizontal cleavage creates baby neurons and occurs more later in development.
The cortex is built from the inside-out, layer VI is the first permanent layer.
Adult neurogenesis is rare, occurring only in the olfactory bulb and hippocampus. It is increased by environmental enrichment, exercise, & socialization. It may never happen in humans.
The Genesis of Connections
Three phases of building long-range connections:
Pathway selection
Target selection
Address selection
The tip of a growing neurite is called the growth cone.
The growth cone contains:
Transmitter storage vesicles
Mitochondria
Microtubules
Actin filaments
Filopodia
Lamellipodia
What a growth cone ‘wants’ can change over time
Chemoattraction leads the neural process toward a point; once arrived, the neuron develops further, developing new sensitivities.
Chemorepulsion drives the neural process to continue past the point.
The Elimination of Cells and Synapses
Neurons in immature visual cortex have about 1.5 times the number of synapses of mature cortex (Huttenlocher and Dabholkar, 1997).
During adolescence, in primate visual cortex, synapses are lost at a rate of 5000/second.
Most of the refinement and experience-dependent plasticity occurs after birth and continues through postnatal life into adulthood.
Between the late prenatal period and adolescence, there is considerable refinement of the architecture of the nervous system.
Much of that refinement involves a dramatic reduction of neurons and synapses (“pruning”).
Neurons projecting to a target region compete for a limited supply of trophic factors, resulting in selective neuronal death.
Synaptic Rearrangement
Synaptic rearrangement involves a change in the pattern of innervation of a target neuron or region (final stage of address selection).
Synaptic rearrangement occurs throughout development.
It occurs based on neural activity and synaptic transmission (is activity-dependent).
Some occurs before birth, but most of it takes place as a result of early experience (sensory and motor) in childhood.
For the “correct” development of the visual system, the quality of the visual environment is critical, especially during a critical period of postnatal development.
Three examples:
Segregation of retinal axons in the LGN
Segregation of LGN inputs in the striate (primary) visual cortex
Synaptic convergence and binocularity
Hebbian learning (named after Donald Hebb): “What fires together, wires together.”
Segregation of retinal axons in the LGN is driven by spontaneous activity of retinal ganglion cells in utero – no light input.
Cells in each eye produce waves of activity that are correlated within each eye but not between eyes.
Hebbian modification ensures segregation in the LGN.
Segregation of ocular dominance columns in striate cortex:
Initially, LGN inputs are intermingled in layer IV of cortex.
Later, LGN inputs segregate into ocular dominance columns.
This is an experience-dependent process: monocular deprivation results in altered patterns of columns. Critical period!!
Cells in cortical layer IV are monocular (receive input only from one eye).
Binocular vision requires convergence onto binocular neurons in layer III.
After monocular deprivation, there is an ocular dominance shift.
The critical period for this type of plasticity extends up to 10 years in humans.
Effect of strabismus (“cross-eyes”) on cortical binocularity: There is almost complete loss of binocular neurons in layer III.
Cortical Synaptic Plasticity: Synapses + electrical activity in development → refinement of synaptic connectivity and synaptic modification.
Two simple rules (really part of a single rule based on correlation):
Consider a simple circuit with two neurons that are connected: A (presynaptic neuron) → B (postsynaptic neuron)
Neuron A and B are both highly activated at the same time → synapse from A to B is strengthened (Hebb’s rule) – “what fires together wires together.”
Neuron A is highly active, but neuron B is only slightly activated → synapse from A to B is weakened – “what fires out of sync loses their link.”