L2 Circuit Development Flashcards
Axonal growth cone
highly specialized structure on axons, forms into presynaptic ending or terminal end of dendrite
highly motile, explore outside environment, sensing what is around the axon, guide the axon
activity is critical for formation of tracts and circuits within the brain
Lamellipodium
sheetlike expansion of the growing axon and its tip
Filopodia
fine processes that extend from each lammelopodium
like little fingers that reach out to test the environment
Filopodia and Lamellipodium makeup
distinguished from axon shaft b/c of specific cytoskeleton molecules (actin and tubulin)
ATP dependent, force generating interactions between the cytoskeleton proteins provides energy and power to propel the growth cone to its target
Chemoattraction
target-derived signals selectively attract growth cones to useful destinations
trophic molecules then help to support the survival and growth of the neurons
Chemorepulsion
chemorepellant signals that discourage axon growth toward inappropriate regions
Dendritic tiling
ensures proper modulation of dendritic growth, makes sure each dendrite occupies appropriate space for axons to synapse onto it
includes: dendrites not growing toward other dendrites from same neuron, dendrites from different neurons are repelled from each other
formation of topographic maps
(maps of neuronal connections)
crushed nerves return to original topographic location, suggests that gradients of cell surface molecules that help growing axons
Trophic molecules and survival
remember that trophic molecules help to support the survival and growth of the neurons
Neurotrophic factors
secreted from from “target tissues”
regulate differentiation, growth, survival
help regulate the phase of neural development that begins once neurogenesis has concluded, including cell death
helps cells to match to the need (remember chicken embryo with arm cut off)
What happens with the first growth cone reaching a new area?
growth cone changes dramatically
lamellipodium expands
numerous filopodia are extended
growth cone changes shape
Axon cytoskeleton
regulates changes in lamellipodial and filopodial shape for directed growth
Microtubule cytoskeleton
responsible for the elongation of the axon
Netrin
chemoattraction molecule
semaphorins
chemorepellant
active during neural development
bound to cell surfaces or ECM, prevent extension of nearby axons
Trophic interaction
long-term dependency between neurons and targets
dependence is based on a signaling molecule provided by target cells, called neurotrophic factors
Why do developing neurons depend so strongly on their targets?
because of the changing scale of the developing nervous system and the body it serves, combined with the need to match the demands of the body
an initial surplus of neural cells are produced
Cell death is programmed for neural cells that do not attach themselves to a target
Synapse elimination
each target cell is initially innervated by axons from several central motor neurons
inputs are naturally lost during early postnatal development until only one axon remains per target cell
the # of synaptic contacts don’t decrease, but actually increase with age
Convergence
number of inputs to target cell
Divergence
number of connections made by a neuron
Examples of where synaptic elimination occurs
autonomic ganglia in PNS
purkinje cells in CNS
What are the 3 essential roles of trophic interactions?
- survival of subset of neurons from larger population
- formation and maintenance of appropriate numbers of connections
- elaboration of axonal and dendritic branches to support connections
What are 3 general themes of neurons and their targets?
- neurons depend on trophic factors for survival and persistence of correct amount of connections
- Target tissues synthesize the trophic factors
- Interneural competition exists for the limited amount of trophic factors
Nerve growth factor
trophic factor
supports sympathetic neurons in vitro
helps match number of nerve cells to number of target cells
Brain derived neurotrophic factor
supports certain sensory ganglion neurons
infleunce synaptic activity and plasticity
Hebb’s postulate
explains the cellular basis of learning and memory
implies that synaptic terminals strengthened by correlated activity during development will be retained or sprout new branches vs ones that lack activity will die
also, coordinated activity between presynaptic and postsynaptic helps to strengthen them
Brain development throughout life
- behaviors not initially present in newborns emerge and are shaped by experiences throughout early life
- Superior capacity for acquiring complex skills and cognitive abilities during early life
- Brain continues to grow after birth roughly parallel with the acquisition of complex behaviors
Postnatal brain growth
due to growth of dendritic and axonal branches, and synapses that parallel the development of complex behaviors
not due to the growth of new neurons
Elimination phase postnatal
the brain continues to grow
continued growth and strengthening of existing synapses, which again parallel the development of more complex behaviors
shows us that the brain is dependent on environment stimuli
Critical periods
the time when experience and the
neural activity that reflects that experience have
maximal effect on the acquisition or skilled execution of
a particular behavior
think of fly away home, how geese couldn’t fly because they didn’t have an actual mom
Critical Periods basic properties
- Encompass a time when behaviors is especially susceptible to environmental influences
- Failure to be exposed to stimuli during critical period makes it almost impossible to gain related skills or neural pathways
- Critical periods rely on changes in organization and function of circuits in cerebral cortex
- Critical periods exist in many sensory systems
When critical period ends
core features of the behavior are largely unaffected by subsequent experience
Neuron growth
human brains do not produce many new neurons once initially formed through early postnatal life
Central nervous system recovery
usually attributed to reorganization of function using remaining, intact circuits rather than repair of damaged brain tissue
Injury and brain
local injury often leads to neuronal death
neural stem cells are retained, most are limited in their ability to divide, migrate, and differentiate
Immune responses and brain
mediated by microglia, astrocytes, oligodendrocytes
release cytokines, which inhibit regrowth of neurons and sometimes axon
Types of neuronal repair
peripheral nerve regeneration
restoration of damaged central nerve cells
genesis of new neurons
Peripheral nerve regeneration
regenerates the axon distally
cell bodies are still intact, but axon has become damaged
most successful of the neuronal repair types
Restoration of damaged central nerve cells
neuron is damaged, but cell survives
new dendrites, axons, synapses have to grow from an exisiting cell body (SPROUTING)
usually a short growth length because glial cells inhibit growth of neurons
Genesis of new neurons
occurs rarely in adults
olfactory neurons regenerate regularly
Henry Head
did a nerve transection on himself
Peripheral nerve repair adult vs embryo
Adult is bigger, axon has to grow a longer length
synaptic target has already been created in adult
Schwann cells and macrophages help secrete molecules that help with reinnervation of targets
Severed vs Crushed
Crushed axon = more rapid recovery
damaged segments still provide a guide
Severed axon = only schwann cells remain and they secrete factors that guide regeneration of intact proximal axons
Schwann Cells and Regeneration
is an essential mediator of axonal growth
-provide molecular support
-recreate an environment similar to before that supports axon guidance and growth
-increase adhesion molecules that help faciliatate growth cone motility, force generation, microtubule assembly in new axon
CNS Regeneration
very little long-distance axon growth or reestablishment of functional connections occur after injury
Different types of CNS injury
Trauma
Lack of oxygen to specific area
Global oxygen deprivation
neurodegenerative diseases
Why isn’t CNS healing as successful as PNS healing?
- Damage to brain tissue leads to necrotic and apoptotic cell death processes
- Cells do not produce signaling that is similar to when the brain/CNS was growing (doesn’t create similar environment)
- Microglial and glial activity inhibit growth
- Upregulation of growth-inhibiting molecules
Glial cells in CNS injury
when injury occurs, all 3 glial cell types are aroused, which opposes neuronal regrowth
produce a glial scar which effectively blocks new growth from the neuron
local growth of glial cells is preserved, macrophages grow abundantly, and neighboring neurons die
Immune-mediated responses after CNS injury
1.Injury damages/disrupts the BBB, tight junctions fail
2. Neutrophils and monocytes are able to enter, which activates microglia, astrocytes, T & B cells
3. Cytokines are released, including interleukin 1. Reinforces the inflammatory state, causing scarring
Neurogenesis in the CNS
there is not SIGNIFICANT neuronal addition after fetal development
interneurons are the main form of neuronal growth, arising from stem cells in ventricles
most new neurons that do grow in an adult brain die before integrating
Plasticity of CNS
idea of functional remapping
the damaged neuron doesn’t grow back, but the neurons surrounding the area change their mapping to cover the area
Nudo article summary
Motor cortex is organized in topographic maps
motor training can change these maps, adaptations occur to take on the new skills/motor patterns
tasks have to be complex or require enough stimulation to cause the adaptation
can be applied to injuries
