Chapter 23: Wiring the Brain Flashcards
brain development begins as ()
tube
wiring in the brain is determined by:
1. nature - ()
2. nurture - ()
- establishing correct pathways and targets by genetic programs
- fine-tuning based on experience and sensory info from envi
organization of the LGN
inputs are segregated by ()
eye and ganglion cell type
() cells give rise to neurons and astrocytes.
Radial glial
neuronal cell structure developes in 3 major stages
- cell proliferation
- cell migration
- cell differentiation
In humans, the majority of neocortical neurons are born between the () of gestation, peaking at the astonishing rate of 250,000 neurons per minutes
5th week and the 5th month
cell proliferation
(1) and (2) during cell division determine fate of daughter cells.
- Transcription factors
- cleavage plane
Ultimate fate of migrating daughter cells determined by the (1) of the precursor cell, its (2), and its (3) at the time of division.
- age
- position
- environment
cell migration
() migrate vertically from the dorsal ventricular zone by moving along thin radial glial fibers.
Pyramidal cells and astrocytes
cell migration
() generate from the ventral telencephalon and migrate laterally.
Inhibitory interneurons and oligodendroglia
cell migration
Radial processes disappear when () is complete
cortical assembly
cell migration
- First cells to migrate take up residence in (1), which eventually disappears.
- Next cells to divide migrate to the (2).
- The first to arrive become layer VI, followed V, IV, and so on: “(3).”
- subplate layer
- cortical plate
- inside out
- Consequence of a specific spatiotemporal pattern of gene expression
- process by which a cell takes on the appearance and characteristics of a neuron
cell differentiation
Order of cell differentiation: ()
neurons, astrocytes (peaks at the time of birth), then oligodendrocytes
evidence for idea that cell differentiaton is rogrammed well before reaching final destination
neural precursor cell will still differentiate even when extracted from brain and placed in tissue culture
(), a protein secreted by cells in the marginal zone, repels the growing axon and attracts the growing apical dendrite, giving the pyramidal neuron its characteristic polarity.
Semaphorin 3A
Adult cortical sheet like a “()”; many structurally distinct areas stitched together; in humans, many specialized cortical areas are precisely stitched
patchwork quilt
Ventricular zone contains cortical ‘()’; migrating cells are precisely guided by radial glial fibers (for majority of cortical neurons)
helps for “patchform quilt” arrangement of cortical sheet
protomap
Some (~1/3) neurons migrate laterally. How? Neurons in different areas have distinct ().
molecular identities
() input contributes to cortical differentiation
Thalamic
- concept that an entire radial column of cortical neurons originates from the same birthplace in the ventricular zone
radial unit hypothesis
In the fetal telencephalon, () are expressed by neural precursor cells in complementary gradients
- sizes of different cortical areas change when these concentration gradients are also changed
Pax6 and Emx2
describe how thalamic inputs are able to influence cortical development
Subplate neurons attract appropriate thalamic axons
3 phases of pathway selection
(1) : which side of the optic tract?
(2) : which nucleus of the thalamus?
(3) : which layer of the LGN (with topography)?
- Pathway selection
- target selection
- address selection
(): growing tip of a neurite
Growth cone
(): constantly probe the environment and direct the
growth of the neurite towards attractive cues.
Filopodia
Neurite growth occurs when a filopodium binds the () and pulls the growth cone forward
substrate (the surface on which it is growing)
Filopodia bind appropriate proteins, such as laminin, in the ()
extracellular matrix (growing axons express integrin that binds laminin)
(): permissive substrates bordered by repulsive ones
Molecular “highway”
(): process of growing axons sticking together by cell adhesion molecules, CAMs, forming bundles of axons
Axonal fasiculation
(“fascicles”) = bundles of axons
() stretch as nervous system expands.
- Guide neighbor axons to same targets
Pioneer axons
Pioneer neurons grow in the correct direction by “()” (a few hundred microns long).
connecting the dots
The pioneering axon concludes a segment when it arrives at an (). The interaction of the axon and the () throws a molecular switch that sends the axon onward to another ().
intermediate target
Growth cones differ in terms of the molecules they express on their membranes -> Interactions of these () with guidance cues in the environment determine the direction and amount of growth
cell surface molecules
diffusible molecules that act over a distance to attract growing axons toward their targets
Growth guidance cues
examples of growth guidance cues
chemoattractant (e.g., netrin), chemorepellent (e.g., slit)
The protein called netrin is secreted by cells in the ventral midline of the spinal cord. Axons with the appropriate netrin receptors are (attracted to/repelled from) the region of highest netrin concentration.
attracted to
The protein called (1) is also secreted by midline cells. Axons that express the protein called (2), the (1) receptor, grow away from the region of highest (1) concentration
- slit
- robo
Up-regulation of robo by axons that cross the midline ensures that they keep growing away from the midline.
(): chemical markers on growing axons are matched with complementary chemical markers on their targets to establish precise connections
Chemoaffinity hypothesis
Large-scale () in neurons and synapses during the process of refining connections (from before birth all the way through adolescence)
reduction
proper development of brain function requires balance between ()
genesis and elimination of cells
and synapses
Autism spectrum disorder: () disorder
neurodevelopmental
Cell death reflects competition for () provided by the target cells; life-sustaining substances that are provided in limited quantities
trophic factors
(): identified in 1940s (released by targets of sympathetic neuronal axon) -> example of trophic factor
Nerve growth factor (NGF)
- (): NT-3, NT-4, BDNF, etc. Bind to trk receptors (tyrosine kinase) altering gene expressions -> family of proteins, including NGF
neurotrophins
programmed cell death; cell death genes are expressed (normally suppressed by trophic factors)
apoptosis
(): the number of synapses a neuron can receive
Synaptic capacity
(): change from one pattern of synaptic connections to another
Synaptic arrangement
involved in critical period
Synaptic arrangement is a consequence of (2)
neural activity and synaptic transmission
both before (spontaneous activity) and after (sensory experience during childhood) birth
- In some circuits, final refinement of synaptic connections requires ()
neural activity
(): whenever a wave of retinal activity drives a postsynaptic LGN neuron to fire action potentials, the synapses between them are stabilized
Hebbian modification -> strengthened synapses are called Hebbian synapses
Visual cortex has () (cat, monkey)—segregated input from each eye (by molecular cues + activity difference)
ocular dominance columns
(): a period after birth when the ocular dominance columns may be modified by activity dependent plasticity (monkey: ~6 wk).
Critical period
dependent on experience
Inputs from two eyes must be combined for () -> Convergence of inputs from layer IV neurons serving the left and right eyes in layer III
binocular vision
(): formed by correlated patterns of activity from two eyes as a consequence of vision (c.f., ocular dominance columns by asynchronous activity from two eyes)
Binocular receptive fields
(): disrupts binocular connections, results in ocular dominance shift
shift may occur within hours (synaptic changes without substantial remodeling of axons)
monocular deprivation
(): inputs from two eyes actively compete for synaptic control of postsynaptic neurons
Binocular competition
(): eyes are not perfectly aligned so that one eye is turned in a direction different from the other eye (cross-eyed or wall-eyed)
Strabismus
Two rules for synaptic modification
– Fire together, wire together (Hebbian modifications)
(pre + strong postsynaptic activation)
– Fire out of sync, lose their link
(pre + weak postsynaptic activation)
A single synapse has little influence on firing rate of postsynaptic neuron -> Activity of a synapse must be () with activity of many other inputs converging on the same postsynaptic neuron for strong postsynaptic activation
correlated
Focus on two glutamate receptors
- () receptors: glutamate-gated ion channels
- () receptors: have unique properties
- AMPA
- NMDA
2 unique properties of NMDA receptors
– Voltage-gated owing to action of Mg2+ (magnesium block)
– Conducts Ca2+
Magnitude of Ca2+ flux into axon terminal signals level of ()
pre- and postsynaptic coactivation
