Lecture 44: Developmental Neurobiology, Postnatal Flashcards
What three processes define the maturation of CNS circuitry?
- Prenatal
When the initial circuits are formed
-circuits are dependent on guidance molecules - Perinatal
- Postnatal
When plasticity and refinement takes place
When the circuits are set in stone
Where can we see the best example of postnatal synapse formation and plasticity?
The visual system is the classic model
How are ocular dominance columns formed? And how is it organized?
Formed perinatally BEFORE experience…formed by endogenous activity
Some monocular columns and some binocular columns as well
How do you determine ocular dominance?
Via terminal labeling
OR
Electrode activity stimulation
What happens when you block vision in one eye?
There are visual defects because the striatal cortical cells do not form very well…even when you open the eye, the recovery doesn’t get back to normal
Known as the “critical window”
Example: if you suture one eye of newborn cat for 12 weeks, and you open it after 12 weeks of life, the undamaged eye will still be unable to see
What is the mechanism for the deprivation of use of normal structure?
The geniculate terminals corresponding to each are in COMPETITION for cortical targets, and the more active terminals from the undeprived eye had a greater edge
What would happen if both eyes were sutured shut?
Ocular dominance forms normally because neither eye had maturation advantage
What is the critical period/window?
The period postnatally where neural circuits are ingrained into the brain
Lack of stimulation during critical period can lead to maturation dysfunction (eyes)
After the critical period, the synapses are permanently changed and set in stone
What happens when you suture one eye in an adult?
The cortical neurons are NOT affected because the critical period had already generated the synapses to the cortices from LGN
What are the features of critical periods?
A. Postnatal period during which nerve connections are shaped by activity (experience) and are sensitive to perturbation
B. Different circuits in the CNS have different critical periods
C. For OD columns in visual system
Lecture emphasis here: 1. Monocular deprivation (MD) causes a shift of OD in V1 toward the non-deprived. This is effective only before certain age. MD has no effect on adult animals
i. monkey: first 6 months
ii. HUMANS: 1st year most important but may extend 5-9 years
2. If MD occurs within the critical period, the effect on ODs is permanent and largely irreversible - implications for surgical care of children with cataracts 3. If MD occurs within the most sensitive part of the critical period (e.g. first 6 weeks in monkeys), just a few days of MD results in a complete loss of vision in the sutured eye
What are other CNS circuits that have critical periods?
Human language = 2-7 years of age….phenome recognition during first year
Social interaction = isolation for 6-12 months leads to behaviorally abnormal people
What is the cellular basis of activity-dependent plasticity during critical periods?
- Mechanisms the weaken and strengthen excitatory synapses
- A balance of inhibition and excitation within the cortex
Cell’s that fire together wire together (long term potentiation)
Neurons out of synch lose their link (long term depression)
Significance: the deprived eye input is uncorrelated with cortical cell activity and there fore will lose the competition (out of sync)
Significance 2: if cells STOP firing (as in if cells stopped firing in the bi-sutured state, then there will be NO FORMATION of ocular dominance, etc.)
Why are inhibitory circuits essential for the critical period?
Why are inhibitory circuits essential for the critical period?
Because without inhibition, there will be inappropriate plasticity
-may provide millsecond modulation of pyramidal cell activity
-allows for competitive interactive between visual inputs
So inhibition circuits OPENS UP critical period
What is our understanding of cellular mechanisms governing the critical period?
The cellular mechanisms governing “critical period” plasticity are incompletely understood, but include:
Hebbian changes in synaptic strength (the fire together wire together and synch-link idea)
A balance of inhibition and excitation
What are the clinical implications of developmental models of plasticity?
Evidence in animal models that “brakes” for critical period can be removed means that there is potential to restore developmental levels of plasticity to treat brain disease
