Neural Development Flashcards
The brain has how many neurons?
10^11
*each of these makes connections with ~1000 other neurons
Describe Phase 1 of the neural development
Different cell types (neurons, glia, muscle cells) develop independently at widely separate locations in embryo according to local program and are unconnected
Describe Phase 2 of the neural development
Axons and dendrites grow out along specific routes setting up a provisional but orderly network of connections between various parts of the system
Describe Phase 3 of the neural development
continues into adult life, connections are adjusted and refined through interactions with distant regions via electric signals
Neurons are produced in association with what type of cells?
glial cells
Provide supporting framework and nutrition
What do neurons and glial cells develop from?
ectoderm from a common precursor
What is the CNS (brain, spinal cord, and retina) derived from?
neural tube
What is the PNS (nerves, sensory neurons) derived from?
From neural crest
What is the neural tube derived from?
a single layered epithelium and starts with a neural groove
How is the neural tube formed?
Single layered epithelium
neural groove
gradually deepens as neural folds become elevated
folds meet and coalesce in the middle line and convert the groove into a closed tube = neural tube
What is the center of the neural tube called?
neural canal
What does the Delta notch signaling control?
differentiation into neurons (lateral inhibition)
What acts as opposing morphogens, causing neurons at different dorso-ventral positions to express different gene regulatory proteins?
Signal proteins secreted from ventral and dorsal side of neural tube
Where do neural crest cells originate at?
At the dorsal end of the neural tube
When do neural crest cells migrate?
extensively during or shortly after closure of the neural tube or neurulation
What do neural crest cells generate?
several differentiated cell types:
- neurons and glial cells of PNS
- epinephrine-producing cells of the adrenal gland
- many of the skeletal and connective tissue components of the head
Describe the migration of neurons
Neurons migrate from their original birthplace and settle in a different location
After final division close to the inner face of the neural tube they crawl along radial glial cells
Radial glial cells extend from inner to outer end of the neural tube
Describe dorsal neurons of spinal cord
Receive and relay sensory information from sensory neurons located in the periphery of the body
Describe ventral clusters of the spinal cord neurons
Develop as motor neurons and send out long axons to connect with specific subset of muscles
Describe intermediate neurons
Intermediate location has inter-neurons that connect specific set of nerve cells to each other
True or False
Axon and dendrites are not distinguishable at first during development?
True
Tip of axon/dendrite has an irregular, spiky enlargement called growth cone
What does the growth cone do?
crawls through surrounding tissue, trailing the axon or dendrite behind
Has an engine and steering apparatus that directs the process along the right path
Behavior dictated by its cytoskeletal machinery
How are axon-specific proteins formed?
one of the growth cone starts migrating fast and develops the proteins and will form the axon
What do growth cone cytoskeletal machinery throw out
filopodia and lamelopodia
What controls the assembly/disassembly of actin filaments, which controls movement of the growth cone?
monomeric GTPases Rho and Rac
Growth cones travel towards target along predictable routes. They exploit two major cues to find their way:
- Extracellular matrix environment sensed by receptors present on membrane
- chemotatic factors released by neighboring cells
Growth cones often follow a path taken by other cells, this is called what?
contact guidance
Consequently, nerve fibers are usually found in bundles
How is contact guidance mediated?
by homophilic cell adhesion
What are two important classes of homophilic cell adhesion molecules?
Immunoglobulin superfamily
cadherin family
*provide a mechanism for selective guidance and recognition
Matrix molecules such as laminin favor what?
axonal growth
Chondroitin sulfate proteoglycans inhibit what?
growth
What are secreted by cells and act as guidance factors at strategic points along path?
Chemotactic factors
Chemotactic factors may be attractive or repulsive. what are some examples?
Netrin
Slit
Semaphorin
Describe netrin effect on the mechanism of commissural neuron guidance
First stage depends on secretion of netrin by cells of the floor plate
Netrin bints to TRPC channels
Entry of extracellular Ca
Activation of machinery for extension of filopodia and movement of growth cone
What neurons in the neural tube do not have netrin receptors, so they do not migrate towards floor plate?
Non-commissural neurons
Describe Slit effect on the mechanism of commissural neuron guidance
Midline cells secrete Slit
Slit receptor = Roundabout (present on commissural neurons)
Slit repels growth cones and blocks entry to the midline
Growth cones become sensitive to semaphorin(repulsive)
Trapped between 2 sets of repellants to travel narrow track
When axonal growth cone reaches eventual target cells what happens?
They halt and communicate and make synapses with target cells
Usually unidirectional signaling in nerve cells but in developing cells bidirectional
Signal from target tissue regulate which grwoth cone synapse and where
How many neurons die after they reach target cell?
50% because they are made in excess
and target cell produces limited amount of specific neurotrophic factors needed for survival
Those that do not get enough die by programmed cell death
*can be reversed by increasing number of target cells and exacerbated by decreasing number of target cells
What was the first prototypical neurotrophic factor to be identified?
Nerve growth factor NGF
Belongs to the family of neurotrophins
Tyrosine kinase NGF receptor
Promotes survival of specific sensory neurons and sympathetic neurons
What are the short term effects of NGF?
Effect on growth cone and neurite extension. Effect is local, direct rapid, and independent of communication with cell body
What are the long term effects of NGF?
Effect on cell survival. mediated by its receptor, uptake into cells via endocytosis and stimulation of downstream signaling pathways
Synaptic remodeling is dependent upon what 2 rules that create spatial order?
- axons from cells in different regions of retina compete for tectal neurons (different times)
- axons from neighboring sites which are excited at the same time cooperate/collaborate to retain and strengthen synapses with tectal neurons
activity - dependent synaptic remodeling depends on what
electrical activity and synaptic signaling
Describe the process on how denser distribution of synapses are formed
Each axon initially branches widely and makes multiple synapses with target cell
Profusion of weak synapses
Network subsequently trimmed by elimination of synapses and retraction of axon branches
Accompanied by sprouting of axons to develop denser distribution of synapses that survive’
Fuzzy initial map -> sharp final map
How is adult memory formed?
Synapses are strengthened by external events that cause 2 or more neurons to be activated at the same time
Entry of Ca through NMDA receptor triggers lasting change in synaptic strength
Corresponding change in physical structure of synapse
Individual dendritic spines remodeled, new spines appear with electrical stimulation
