Lecture #3 Flashcards
what is the process called in which there is the generation of the neural tube soon after gastrulation?
neurulation
soon after the closure of the neural tube what subset of cells is generated?
neural crest cells → will go on to generate different different types of cells including sensory ganglia, parasympathetic and sympathetic outflows, myelin of the PNS and skull
what is the initial subdivision of the CNS?
brain and spinal cord
inside the brain at the beginning of development, there is the formation of three rudimentary vesicles, what are they?
prosencephalon (anterior), mesencephalon (intermediate), and rhombencephalon (posterior)
as development occurs, the three original vesicles turn into five - what are the new divisions?
prosencephalon: telencephalon → cerebral cortex and corpus striatum (from the basal region of the telencephalon)
diencephalon that connects tissues between the telencephalon and the subtelencephalic regions composed of the thalamus, hypothalamus, and epithalamus
what two divisions will come from the rhombencephalon?
metencephalon (forms the pons and cerebellum) and myelencephalon (medulla oblongata: part of the CNS connecting the brain with the spinal cord)
what is the most important concept of the brain differentiation during development?
dramatic elongation and tangential expansion of the two tele cephalic vesicles, that will general the two cerebral hemispheres
the telencephalon vesicles connect to the diencephalon, and are composed of two half - what are they?
dorsal half: pallium
ventral half: striatum
why is the striatum important?
its a sort of tissue that can modulate the firing and functional activity of the telencephalic vesicles → receives a huge amount of information from telencephalon vesicles and modulates this information
describe the crossroads in the striatum:
allows the cortex to send messages to the spinal cord and vice cress so the cortex can receive information from the periphery
what are the two early developmental regions of the striatum?
medial and lateral ganglia eminences
what are the two subdivisions of the cortex of the early striatum?
piriform cortex: specific part of the telencephalon vesicle that manages olfactory impulse
hippocampus
what is another term used to refer to the two subdivisions of the cortex?
allocortex
in mammals, how many layers make up the neocortex?
6
what four structures help to protect the embryo?
- placenta (filter)
- amniotic cavity
- yolk sac
- allantoid (important for gas exchange between the embryo and the placenta)
what is an example of a virus that can cross the placenta and affect the embryo?
Rubella
which mosquito is a carrier able to transmit Zika virus?
aedes aegypti
what are the main symptoms of Zika?
myalgia, maculopapular rash, arthralgia, and sometimes cardiovascular abnormalities
some patients starting from the micropolynesia outbreak we also have Guillian-Barré syndrome
what is Guillian-Barré syndrome?
a rare and sever disease that occurs after an acute infectious procedure affecting the PNS
if we have an inflammatory neuropathy in the PNS we start to lose tendon reflex and have severe weakness, and in severe cases also failure of the respiratory muscles
what is the current therapeutic strategy for Guillian-Barré syndrome?
aphaeresis of immunoglobulin or the administration of specific immunoglobulin to block the pathologic activation of the immune system
what is the main etiology of Guillian-Barré syndrome?
campylobacter jejuni: activation of the immune system and for the mimicry, the immune system starts to attack the myelin of the PNS causing this tremendous disorder
what are the three lineages of Zika?
- Asian / American: Brazil, Columbia, Guatemala - associated with severe microencephaly
- African lineage I: not associated with microencephaly or Guillian-Barré syndrome
- African lineage II: well investigated
what did scientists find when they did an experiment on a fetus with Zika in 2016?
calcification over the white matter of the brain, severe hypo development of the cerebral cortex, and an increased size of the ventricular cavity
what specific morphological differences did they find in the brain of the fetus?
very few sulci and gyri - the brain was very smooth and the neuroepithelial cells did not tangentially expand
also an accumulation of immune cells in the brain indicating an inflammatory reaction
what were some models used to study Zika?
- iPSCs derived from human neuroepithelial cells → proved the Zika can affect neuroepithelial cells
- spheres
mice → similar brain development and large potential for genetic manipulation - organoids
what specific protein is normally located in cells near the mitotic spindle that is important for the organization of the spindle and therefore for symmetric cell division?
TBK1
what happens to the TBK1 protein in the case of Zika virus?
TBK1 translocates from the spindle region to the mitochondria because it is also involved with the antiviral response
When TBK1 is in the mitochondria it can’t work in the spindle and this causes aberrant formation of the mitotic spindle leading to an altered cell division that causes the apoptosis of cells
what were neurospheres used to discover?
the ZIKV(BR)-infected neurospheres displayed evident morphological abnormalities and underwent a dramatic drop in their dimensions allowing the observation of a huge accumulation of apoptotic cells
what cell membrane protein does Zika interact closely with?
AXL
what is the function of AXL cells in Zika?
expression is confined only to neuroepithelial cells and can enter the cells via AXL
besides AXL, what is another receptor Zika can enter by?
DC sign which is a transmembrane protein normally expressed by myeloid cells, but in the developing brain it is expressed by neuroepithelial cells
who divided the human cerebral cortex into 52 different areas, and what were these divisions based on?
Brodmann in 1909
cytoachitecture and functionality
what is the development program that allows for the generation of this complex diversity?
realization or regionalization
10 years after Brodmann, Vogt further subdivided the human cerebral cortex into what two territories?
isocortical and allocortical territories
what is the isocortical territory?
the major part of the telencephalon - show 6 layers of development and is a neocortex (invention of animals)
what is the allocortex territory?
olfactory system and hippocampus, with the three subtypes of allocortexes called the paleocortex, archicortex, and periallocortex - three layers of development
what is the main area of the archicortex?
hippocampus: very important for spatial navigation of animals and humans and for the fixation of very fresh information in the brain
what is the mesocortex?
the periallocrotex and the prosicortex (along the borders of the isocortex) - forms the transitional zone from the there layer cortex to the six layer cortex
describe the first layer of the neocortex:
largely composed of axons and apical dendrites of pyramidal cells that are needed to connect different regions inside the brain
describe the second layer of the neocortex:
containing mainly small pyramidal cells
describe the third layer of the neocortex:
containing small and medium sized pyramidal cells which together with those in layer II, given rise to the associated and commissural fibers
going forward in the layers of the neocortex, how do the cells change?
the number of cells goes down but the cells increase in dimension
what region are cortical neurons generated from?
ventricular zone neuroepithelial cells → generated in two distinct waves of cell proliferation and subsequent migration from the germinal niche to the regions to far from the basal membrane
where are the first cortical neurons generated?
in the preplate located above the germinal niche
describe the human brain in terms of texture:
gyrencephalic
how long does it take the cortical plate to form in humans vs mice?
6 days in mice, 100 days in humans
according to Brodmanns categorization, what do areas 1, 2, and 3 represent in the brain?
the primary somatosensory cortical area → neurons from this area receive info from the periphery and start to elaborate on it
according to Brodmanns categorization, what do areas 4, 6, and 8 represent?
the motor cortex → in this are there are the first mortar neurons that sent long axons from the cortex to the spinal cord and to a second motor neurons that connects the spinal cord with the muscles
according to Brodmanns categorization, what do areas 17, 18, and 19 represent?
the visual cortex → where the optic input from the eyes is analyzed
according to Brodmanns categorization, what does area 10 represent?
the prefrontal region → important for the generation of thinking
which part of our brain is importation for our interaction in a social environment?
anterior portion
what process links the initial telencephalon vesicles with the adult brain?
regionalization and realization of the cerebral cortex
in humans, what additional series of proliferating neuroepithelial cells are present that help with the creation of the gyrencephalic brain?
basal progenitor cells
what are basal progenitor cells?
proliferating cells that can undergo symmetric and asymmetric divisions, but are different from neuroepithelial cells because they lack the connection with the apical membrane → they are connected only to the basal membrane
these cells only proliferate in the outer sub-ventricular zone (not the germinal niche)
what does the presence of basal progenitor cells in the outer sub-ventricular zone cause?
starts to bend the cortex and their presence is enough to perform a gyrification
describe striatum neurons:
neurons derived from neuroepithelial cells proliferating in the germinal niche of the striatum, that start to migrate and differentiate into different neuronal cell types
why is the striatum important?
it is a region where a huge number of fibers are running up and down, so if something perturbs these axons the ability of the cortex to interact with the subcortical region is altered
what disease causes shaky movements as a result of lack in regulation of the striatum?
Parkinsons
what are the three broad classes of projection neurons that have been described as cortical excitatory neurons?
cortico-thalamic neurons
pyramidal tract neurons
intra-telencephalic (IT) neurons
describe cortico-thalamic neurons:
project into the thalamus and occupy layer VI
describe pyramidal tract neurons:
send long projections that enter into different cortical regions (especially the spinal cord) but often possess collateral projections to the thalamus an medulla
mainly occupy layer V
called pyramidal because the cell body of these neurons is a triangle
describe the intra-telencephalic neurons:
connect different regions of the cortex
layers II-VI
describe the three subcortical regions of the thalamus:
- surface: send their axons only to cortical neurons that are in the occipital to caudal pool
- middle: receive information from the thalamic nuclei
- deep: send their axons through the striatum and enter contact with neurons present only in the frontal part of the cortex
what does regionalization modulate?
the proper development as well as govern how something that is coming from the outside enters and interacts with the cortex
what were the two models for neocortical development?
Intrinsic model (Rakic) and Extrinsic model (O’Leary)
describe the intrinsic model (Rakic):
arealization is the resist of the characteristics of the neocortex itself based on proper information available inside of the cortex and neuroepithelial cells that have all the instructions to build a regionalized cortex
protomap theory: neocortex differentiates automatically during development according to genetic controls
describe the extrinsic model (O’Leary):
protocortex hypothesis: the neocortex is undifferentiated until the thalamus directs particular neural signals to a particular neocortical area causing subdivisions to form
which model for neocortex development won?
the protomap hypothesis → based on transgenic animal models it is clear that the fine-tuning of specific regions of the cortex invite is based on inputs that come from the periphery
