Development of the CNS Flashcards

1
Q

What is the origin of the NS ?

A

Simple ectodermal tube

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2
Q

When does development of the NS begin ?

A

Development begins around the third week of gestation when a longitudinal (rostral–caudal) band of ectoderm thickens to form the neural plate

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3
Q

How is formation of the neural plate triggered ?

A

Neurulation is induced by notochord (primary inductor in the early embryo, located deep to the neural epithelium)

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4
Q

Describe the transformation of the neural plate to a tube.

A

END OF WEEK 3
- A midline groove soon appears on the posterior surface of the neural plate, and the neural plate begins to fold inward

  • As the groove deepens, neural folds appear on each side of the groove
  • These folds then begin to approach each other, and by the end of the third week of development, the neural folds begin to fuse (around the cervical segment level), forming a neural tube (process aided by apical constriction)
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5
Q

Identify possible consequences of the failure of the neural tube to develop.

A

If a portion of the neural tube fails to develop or the neural folds do not close completely, this may result in Neural Tube Defects (NTDs):

1) Anencephaly: failure of neural tube to close (at the rostral neuropore), resulting in absence of forebrain (cerebral hemispheres absent)
2) Spina bifida: failure of neural tube to close (“somewhere along the spine”), resulting in defects in the spinal cord and in the bones of the spine

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6
Q

Identify the main sites of spina bifida.

A

The most common location of spina bifida is the lower back, but in rare cases, it may occur in the middle back or neck and may result in a wide range of physical and cognitive disabilities.

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7
Q

Describe further development of the neural tube into the next structures.

A

The rostral end of the neural tube develops into the brain, and the remainder develops into the spinal cord

Fusion of the neural tube occurs from the middle out toward the rostral and caudal ends, and as it occurs, cells from the top or crest of each neural fold dissociate from the neural tube (neural crest cells) (undergo epithelial to mesenchymal transition, lose contact with BM, become motile, and start to migrate into the mesoderm).

As the neural tube closes (rostral neuropore closes on day 25, caudal neuropore closes on day 27), it separates from the ectodermal surface and thus becomes enclosed within the body.

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8
Q

What types of cells do the neural crest cells that dissociate from the neural tube become ?

A

These neural crest cells migrate away from the neural tube epithelium and differentiate into a variety of cell types including:

  • Sensory neurons in the ganglia of the spinal nerves
  • Some cranial nerves (V, VII, VIII, IX, and X)
  • Postganglionic neurons of the autonomic nervous system
  • Schwann cells of the peripheral nervous system (PNS)
  • Adrenal medulla

-Smooth muscle of cardiac outflow

  • Odontoblasts,
  • Craniofacial skeleton
  • Thyroid parafollicular cells
  • Melanocytes
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9
Q

Define neurulation.

A

Formation of the neural plate and closure of the neural folds and neuropores to form the neural tube.

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10
Q

Identify the main clinical features, and risk factors of Anencephaly.

A
  • Usually unreactive to light and sound
  • Usually stillborn
  • Some infants may exhibit respiration and respond to touch and sound

RISK FACTORS

  • Folate deficiency (folate precursor in DNA synthesis, so if deficient, might have some defect in cell division)
  • Previous anencephaly
  • Diabetes
  • Epilepsy drugs
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11
Q

Identify the main types of spina bifida.

A

A) Spina Bifida Occulta:
defect in the bony spinal canal without protrusion of the cord or meninges.
B) Meningiocele: hernial protrusion of meninges through a defect in the bony spine
C) Meningomyelocele: protrusion of the spinal cord and meninges through a defect of the vertebral column
D) Myeloschisis: most severe form of spina bifida, due to failure of caudal neuropore to close, resulting in cleft spinal cord (neural tissue is exposed)
E) Myeloschisis (but with folded (still exposed) neural tissue)

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12
Q

Identify another pathological abnormality associated with NTDs.

A

Associated with displaced cerebellum with hydrocephalus

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13
Q

Identify a factor which may reduce risk of neural tube defects.

A

Supplementing maternal diet with folate reduces risk of neural tube defects

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14
Q

Identify a marker for neural tube defects.

A

Alpha fetoprotein (AFP) is a “disease” marker for neural tube defects/some cancers/liver disease

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15
Q

When does development of the brain begin ? How does it begin ?

A

Development of the brain begins during the fourth week of gestation when differential growth results in enlargements (primary, then secondary vesicles) and bends (flexures) in the neural tube.

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16
Q

Identify the primary vesicles.

A

Three primary vesicles appear at the rostral end of the neural tube:
-Prosencephalon (which becomes the forebrain)
-Mesencephalon (which becomes the midbrain
-Rhombencephalon (which becomes the hindbrain),
the latter merging with the spinal portion of the neural tube
(these are curved, rather than straight)

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17
Q

Describe further development of the primary vesicles, including ventricles.

A

Around the fifth week, five secondary vesicles appear:

From the prosencephalon (forebrain):

1) Telencephalon (AKA endbrain AKA cerebral hemispheres)
2) Diencephalon (AKA between brain AKA thalamus, hypothalamus, and subthalamus)

3) The mesencephalon (midbrain) (grows slower than forebrain) remains undivided.

From the rhombencephalon (hindbrain):

4) Metencephalon (pons and cerebellum, latter formed from posterior part of metencephalon)
5) Myelencephalon (medulla)

VENTRICLES (all connected)
Two lateral ventricles are associated with the telencephalon, one in each cerebral hemisphere. “C” shaped, due to the curvature of the brain during embryonic development. Both connected to third ventricle via Interventricular foramen of Munro). The third ventricle is associated with the diencephalon, and the thalamus and hypothalamus are located on either side of the third ventricle.

The third ventricle is connected to the fourth ventricle through the cerebral aqueduct (which passes through the midbrain). The fourth ventricle is associated with the hindbrain and lies between the cerebellum and the pons and medulla

Lumen of the tube contains CSF.

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18
Q

Describe development of the cerebral hemispheres.

A

As development proceeds, the hemispheres expand anteriorly to form the frontal lobes, laterally and superiorly to form the parietal lobes, and posteriorly and inferiorly to form the occipital and temporal lobes.

Growth and expansion continue and result, ultimately, in the cerebral hemispheres taking on the shape of a great arc or “C” that covers the diencephalon, midbrain, and pons

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19
Q

Identify the main structural divisions of the brain.

A

The part of the CNS within the skull cavity is referred to as the brain. It consists of the forebrain (from the prosencephalon), the midbrain (from the mesencephalon), and the hindbrain (from the rhombencephalon). The forebrain consists of the cerebral hemispheres and deep structures. The midbrain and hindbrain are collectively referred to as the brainstem, with the hindbrain further divided into the pons, medulla, and cerebellum.

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20
Q

Draw a diagram of the developing brain including ventricles, and the structures surrounding them.

A

Refer to slide 21 in lecture on “Development of the CNS”

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21
Q

Explain the reason for the curvature of the brain, including internal structures.

A

“The cerebral hemispheres and lateral ventricles become C-shaped as a result of the non-uniform expansion of the telencephalon. As the frontal, parietal, temporal and occipital lobes grow the telencephalon expands like an inflating balloon. A small island of tissue overlying the basal ganglia expands comparatively little and is progressively ‘swallowed up’ by the surrounding frontal, parietal and temporal lobes (opercula of cortex from each adjacent lobe cover the insula). This region corresponds to the insula, which is hidden within the depths of the lateral sulcus in the mature brain.

As the telencephalon continues to expand it eventually envelops and fuses with the diencephalon. Once this has happened, axons can pass directly between the cerebral hemispheres and brain stem, traversing the basal ganglia and partially dividing them. Many internal hemispheric structures are distorted by the expansion of the cerebral hemispheres and take on the same C-shaped profile as the lateral ventricles. These include the hippocampus and its outflow pathway, the fornix.” Also include Corpus Callosum, interventricular foramen, Caudate Nucleus.

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22
Q

Define cephalic flexure.

A

the sharp, ventrally concave bend in the developing midbrain of the embryo.

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23
Q

Identify the main brain lobes and grooves.

A
FRONTAL LOBE
Central sulcus
PARIETAL LOBE
Parieto-occipital sulcus 
OCCIPITAL LOBE
Pre-occipital notch
TEMPORAL NOTCH 

Lateral fissure (“separates the frontal and parietal lobes from the temporal lobes, insular cortex lies deep within the lateral sulcus”)

24
Q

What is the function of gyri ?

A

Gyri increase surface and volume of grey matter

25
Q

When do brain lobes and groove become evidence ?

A

At full term.

26
Q

Describe the anatomical location of the lateral ventricles.

A

“Begins in the temporal lobe, travels through a body in the parietal lobe and frontal lobe, and ultimately terminates at the interventricular foramina where each lateral ventricle connects to the single, central third ventricle”

27
Q

What is the function of the fornix ?

A

Connects hippocampus with anterior structures

28
Q

What is the function of the Corpus Callosum ?

A

Connects the two cerebral hemispheres

29
Q

What is the main function of the hippocampus ?

A

Role in memory

30
Q

What lobe is the hippocampus located in ?

A

Temporal lobe

31
Q

What is the role of the Interventricular foramen of Monro ?

A

Fluid filled space

32
Q

Describe the anatomical location of the fornix.

A

Loops around the III ventricle and diencephalon, connects hippocampus with anterior structures

33
Q

Identify the fornix, Corpus Callosum, Lateral ventricle, Hippocampus, and Interventricular Foramen on a sagittal plane of the brain.

A

Refer to slides 31 and 32 of lecture “Development of the CNS”

34
Q

Identify the fornix, Corpus Callosum, Lateral ventricle, Hippocampus on a coronal plane of the brain.

A

Refer to slide 33 of lecture “Development of the CNS”

35
Q

What is the Caudate Nucleus ?

A

An elongated, arched gray matter mass closely related to the lateral ventricle throughout its entire extent, which, together with the putamen, forms the neostriatum (it’s a basal ganglion). Functions in motor control.

36
Q

What is a basal ganglion ? Identify its main structural components.

A

Any of several masses of gray matter embedded in the cerebral hemispheres that are involved in the regulation of voluntary movement.

1) Caudate Nucleus (head is located in the floor of the lateral ventricle and the body arches over the thalamus in a C shape tapering off into a tail located in the roof of the inferior horn of the lateral ventricle)
2) Putamen (most lateral of the basal ganglia and embryologically is connected to the caudate nucleus)
3) Globus pallidus (medial to the putamen and lateral to the thalamus)
(putamen and GB make up lentiform nucleus)
4) Substantia nigra (SN)
in the rostral midbrain
5) Subthalamic nucleus (STN)
located inferior to the thalamus

37
Q

Describe the separation of the different parts of the basal ganglia.

A

“The internal capsule is a white matter structure situated in the inferomedial part of each cerebral hemisphere of the brain. It carries information past the basal ganglia, separating the caudate nucleus and the thalamus from the putamen and the globus pallidus”

38
Q

Identify the basal ganglia, Lentiform nucleus, Caudate Nucleus, and Internal Capsule on a transverse plane of the brain.

A

Refer to slide 35 of lecture “Development of the CNS”

39
Q

What is the function of the amygdala ? Is is part of the basal ganglia ?

A

Nucleus at the front of the temporal lobe. The amygdala is concerned with memory registration.
No

40
Q

Draw a typical basal ganglion, along with its main structural components (+ internal capsule, amygdala and thalamus).

A

Refer to slide 36 in lecture “Development of the CNS”

41
Q

Identify the C Nucleus, Internal Capsule, L ventricles, Lentiform Nucleus on a coronal slice.

A

Refer to slide 37 in lecture “Development of the CNS”

42
Q

Explain how the fourth ventricle forms.

A

Around 6 weeks, a dorsal fold develops in the rhombencephalon (pontine flexure) that divides the rhombencephalic vesicle into the myencephalic vesicle (the myelencephalon becomes the caudal part of the 4th ventricle, i.e., the medulla) and the metencephalic vesicle (the metencephalon becomes the rostral part of the 4th ventricle, i.e., the pons).

While this is happening, the back of the brainstem opens out. This means that the sensory grey matter goes from dorsal position (before IV ventricle forms) to more lateral.
(find motor grey matter medially)

43
Q

Is cerebellum white or grey matter ?

A

Grey matter

44
Q

Draw a transverse section showing the IV ventricle, choroid plexus, sensory and motor grey matter.

A

Refer to slide 41 in lecture “Development of the CNS”

45
Q

Describe the main developmental events in the wall of the fourth ventricle.

A

As fourth ventricle opens out, two events happen in its wall:

  • Near tail end, choroid tisue develops (makes CSF)
  • Rostrally, cerebellum develops
46
Q

Label a dorsal view of the brainstem with cerebellum removed.

A

Refer to slide 42 in lecture “Development of the CNS”

47
Q

What are the functions of the superior and inferior colliculus ? Where are they located ?

A

Both located in the midbrain.

Superior colliculus: “part of the brain circuit for the transformation of sensory input into movement output. Its major function is orienting the animal, particularly with eye movements, to objects of interest in the outside world”

Inferior colliculus: “principal midbrain nucleus of the auditory pathway and receives input from several peripheral brainstem nuclei in the auditory pathway, as well as inputs from the auditory cortex.”

48
Q

What are the functions of fasciculus cuneatus and gracilis ?

A

Gracilis: bundle of axon fibres that carries sensory information from the lower part of the body to the brain stem

Cuneatus: bundle of axon fibres that carries sensory information from the higher part of the body to the brain stem

49
Q

Where do the cranial nerves exit the brainstem ? Where do craniel nerve nuclei tend to be ?

A

Cranial nerve nuclei tend to be dorsal, most cranial nerves exit ventrally, (10 from BS from dorsal grey matter). Trochlear (IV) is the only nerve to emerge from the posterior surface of the brainstem.

50
Q

Describe development of the spinal cord.

A

Caudal end of the neural tube “forms a narrower tube of relatively the same size along its length that will eventually form the spinal cord.”

This tube has an inner ventricular layer (progenitor cells- neurons/glia), cell division in which provides neurons/glia of the middle mantle layer (contains neuron bodies/glia. The outer marginal layer contains processes of neurons (refer to slide 44 of lecture).

As the neural tube develops, changes take place that differentiate the orientation of spinal cord functional elements from brainstem functional elements. The neural tube has an alar plate (AKA alar lamina), positioned dorsally (will be posterior), containing the sensory components, and a basal plate (AKA basal lamina), positioned ventrally (will be anterior), containing the motor components of the nerves (both in the mantle layer, i.e. grey matter). These two plates are separated by a groove called the sulcus limitans. This arrangement is consistent throughout the spinal cord, where sensory information is located in the posterior gray horn and motor information is located in the anterior gray horn. Of note, visceral sensory and visceral motor information are both located closest to the sulcus limitans.

Changes occur in this arrangement as the brainstem begins to develop. In the caudal area of the brainstem, specifically in the area that will become the rostral or open medulla, the central canal widens to form the fourth ventricle. As this occurs, the alar plates move out laterally. The sulcus limitans still separates the alar and basal plates. Sensory components (including somatic and visceral) of the cranial nerves are now located lateral (rather than posterior) to the sulcus limitans, whereas motor components (including somatic and visceral) are now located medial (rather than anterior) to the sulcus limitans. In the rostral pons, the fourth ventricle narrows down as the cerebral aqueduct forms. At this point, the alar plate rotates back to a more posterior position relative to the basal plate.

51
Q

State whether each layer of the caudal neural tube is grey or white matter.

A

Mantle- grey matter

Marginal- white matter

52
Q

State whether the following is white or grey matter:

  • Hippocampus
  • Fornix
  • Corpus Callosum
  • Basal ganglia
  • Putamen, GB, Lentiform Nucleus
A
  • Hippocampus: Grey Matter
  • Fornix: White Matter
  • Corpus Callosum: White Matter
  • Basal ganglia: Grey Matter
  • Putamen, GB, Lentiform Nucleus: Grey Matter
53
Q

Describe how connections form between the PNS and the spinal cord.

A

1) Ingrowth of neurites from dorsal root ganglion cells (DRG)
forms dorsal root

2) Outgrowth from neurons motor grey
forms ventral root

Sensory information enters the spinal cord through the dorsal/posterior roots. Sensory cell bodies are located in the dorsal root ganglion of each spinal nerve (DRG cells come from neural crest cells).
Motor information leaves the spinal cord through the ventral/anterior roots (to peripheral musculature)

The anterior root does not contain a ganglion.

Distal to the dorsal root ganglion, the fibers of the anterior and posterior root merge together and pass through the dura to become the spinal nerve. Because the spinal nerves contain both sensory and motor fibers, they are considered a mixed nerve, as opposed to either a sensory or motor nerve (there is a descending)

54
Q

Draw a segment of spinal cord, along with all tracts, neurons and pathways present. Denote the parts which are grey, and white matter.

A

Refer to slides 47 and 48 in lecture on “Development of the CNS”

55
Q

What induces the neural tube formation and nerve cell specialisation?

A

Notochord important for inducing neural plate. Noggin, chordin, follistatin produced in the notochord block BMP allows default differentiation of neural ectoderm (without this, Bone morphogenetic protein inhibits neural ectoderm, promoting skin)

56
Q

Identify pathologies associated with defective neural crest development, stating the main clinical features of each and the genetic pattern of inheritance.

A

1) WAARDENBURG’S SYNDROME (autosomal dominant, some due to Pax-3 gene deletion, leading to failure of neural crest to develop properly)

  • Pigment abnormalities (even albinism) (melanocyte defect)
  • Deafness (cranial nerve ganglia defect)
  • Constipation (autonomic ganglia defect)
  • Heterochromia of eyes
  • Telecanthus

2) TREACHER COLLINS SYNDROME (autosomal dominant, due to defective protein called Treacle, FCOF1 gene, leading to failure of formation/apoptosis of neural crest cells)

  • Abnormal eye shape
  • Micrognathia
  • Conductive hearing loss,
  • Underdeveloped zygoma
  • Malformed ears