WEEK 1

Question 1

levels of neurodevelopment

Answer 1

1) the systems level: looking at the changes in size and shape in the development of the NS - “MORPHOGENESIS”

2) the cellular level: differentiation from progenitors into mature neurons

Question 2

neural induction

Answer 2

a portion of the ectoderm or germ layer (the neural plate) is induced to become neural tissue under signals of the mesoderm. this forms the nervous system.

Question 3

neurulation

Answer 3

as the ectoderm becomes neural tissue, it also undergoes morphogenic changes in shape.

Question 4

morphogenesis at the tailbud stage

Answer 4

at the tailbud stage, cranial, cordial, and lateral folding occur. These give the body a comma shape, enclose the organs in ectoderm (skin), and we start to see a head, tail, somite blocks and branchial arches (jaw and neck) + limb buds later on in development. so the major structures of the developing embryo appear by 4-5 weeks.

Question 5

telencephalon

Answer 5

subdivision of the forebrain which gives rise to most of the cerebral hemispheres via an extensive folding process during neurodevelopment.

Question 6

diencephalon

Answer 6

subdivision of the forebrain which gives rise to important collections of neurons such as the thalamus.

Question 7

differentiation

Answer 7

cells progress from a multipotent population to cells of particular specialized identities or fate. we can think of cell differentiation as a decision tree, which will eventually lead to cells assuming one of a number of fates.

Question 8

Waddington (on differentiation)

Answer 8

represented differentiation as a ball rolling down a hill, the epigenetic landscape, and then rolling into one of a number of channels. which channels it ends up in is not random, it depends on interactions which instruct cells on their next developmental step. ex: neural induction of the neural plate.

Question 9

aspects of neural differentiation

Answer 9

1) the appearance or morphology of individual cells. ex: purkinje cells have elaborate spines, whereas pyramidal cells do not

2) the gene expression profile

3) neurotransmitter type

4) axon projections and connectivity to other neurons in the NS.

Question 10

developmental steps that lead to differentiation

Answer 10

1) neurogenesis: cell division generates neurons

2) cell migration: young neurons migrate out of the ventricular zone

3) axogenesis: young neurons develop axons that grow out towards targets

4) synaptogenesis: axons make contact with their target neurons and other structures

5) cell death/pruning: regression events leading to the formation of mature neurons

Question 11

radial glial cells and the neural tube during neurogenesis

Answer 11

radial glial cells are the progenitor cells of the NS. they undergo cell divisions to expand the progenitor cell population.

once a neuron is generated, it will migrate along the radial glial cells, using them as a guide towards the mantle zone where further differentiation occurs (axon extension).

Question 12

three types of neuronal migration

Answer 12

1) radial migration (spinal)

2) tangential migration

3) neural crest cells

Question 13

radial migration

Answer 13

in the forebrain, cells which migrate radially along radial glia give rise to neurons with long axons which project to other regions of the NS and which use glutamate. these are “excitatory projection neurons”.

Question 14

tangential migration

Answer 14

in the forebrain, cells which migrate orthogonal to the radial axis, and intermingle with the neurons that have undergone radial migration. tangential cells give rise to neurons with short axons which use GABA. these are “inhibitory interneurons”.

Question 15

neural crest cells

Answer 15

cells that split off from the ectoderm while neurulation is underway, migrating away from the forming neural tube to form elements of the PNS (basal root ganglia, sympathetic ganglia, cranial ganglia).

Question 16

stages of axogenesis

Answer 16

1) neurons are round blobs

2) neurons look radially symmetrical with several neurites

3) one of the neurites becomes elected as an axon in a process of symmetry breaking

4) the axons grows and dendrites start to form out of the cell body

5) the dendritic tree becomes more elaborate, with dendritic spines forming

Question 17

types of axon connections

Answer 17

1) axodendritic

2) axosomatic

3) axoaxonic

Question 18

neuroligins, neurexins and synaptogenesis

Answer 18

neurologins and neurexins are families of proteins that are expressed by postsynaptic and presynaptic neurons. they bind the pre and post synaptic parts of the synapse together, and recruit specialized groups of proteins to form the synapse.

Question 19

cell death and pruning

Answer 19

cell death: either the elimination of whole cells or parts of cells, axons, synapses, or dendrites. around 50% of motor neurons die later on in development.

pruning: from 4 to 6 years, synapse pruning and consolidation takes place and a decrease in the complexity of the brain occurs. pruning can also occur to axons and dendrites.

Question 20

cell death and pruning: functions

Answer 20

1) eliminate unwanted or aberrant neurons or connections

2) match numbers of pre and post synaptic cells

3) ensure that synaptic transition and circuit function are optimized

Question 21

neurodevelopmental disorders

Answer 21

• ASD
• schizophrenia
• childhood onset epilepsy
• x-linked mental retardation

caused by gene mutations that affect dendrite and synapse development, axon growth, guidance, neuronal migration, synapse formation, and function.

Question 22

synaptogenesis and ASD

Answer 22

mutations in the Neuroligin 4 gene are linked to ASD. Nlgn4 knockout mice show that markers of inhibitory synapses are reduced in some areas of the hippocampus + social interaction and communication impairments, as well as repetitive behaviors or interests.

Question 23

dendritic spines and schizophrenia

Answer 23

individuals with schizophrenia show reduced dendritic spines in the dorsolateral PFC. this reflects defects either in the process of dendritic development and/or pruning.

Question 24

convergence

Answer 24

the ability of different cells to send their inputs to a single target cell - so the single cell is receiving input from multiple sources. the average neuron in the brain receives 10k inputs from 10k synapses.

Question 25

divergence

Answer 25

the ability of a single cell to project to multiple cells. there are up to 1k different axon terminals from one single neuron.

Question 26

functional division of the NS

Answer 26

1) CNS: brain + spinal cord

2) PNS: autonomic (unaware) NS and somatic (aware) NS.

• this view has limitations tho

Question 27

autonomic NS

Answer 27

1) parasympathetic component (“rest and digest”, tho there are limitations to that)

2) sympathetic component (“fight or flight”, still, limitations)

ex: parasympathetic constricts the pupil in bright light. sympathetic dilates the pupil in darkness.

Question 28

CNS or PNS neuron?

Answer 28

if a neuron is entirely contained within the brain and/or spinal cord, it is a CNS neuron. if any part of it (dendrites, axon, or cell body) projects outside these structures, it is a PNS neuron.

Question 29

3 planes of the brain

Answer 29

1) horizontal, transverse sections

2) sagittal, runs through the midline

3) frontal, parallel with the plane of the face

Question 30

CNS: anatomical components

Answer 30

1) the spinal cord, which ends at the base of the skull

2) the hindbrain, made up of the pons, cerebellum and medulla

3) the midbrain

4) the forebrain, which represents the cerebral hemispheres

Question 31

cauda equina

Answer 31

“the horse’s tail”: any nerve below L1 and L2 has to travel down the spinal cord until it finds its corresponding foramen and exits. so there’s a group of nerves at the base of the spinal cord where there’s no tissue or cell bodies involved. this is clinically important because a needle can be placed here without damaging the spinal cord.

Question 32

brainstem: functions

Answer 32

• most important part of the brain. “brainstem death” refers to whether someone is capable of independent life or not
• ascending somatosensory and descending motor pathways going through it, as well as important cerebellar connections
• houses most cranial nerve nuclei
• important center for chemoreception and reflexes
• life-supporting processes such as respiration and arousal centers
• 3 nuclear groups: raphe (serotonin site), locus coeurulus (adrenalin site), and substantia nigra (dopamine and movement control site)

Question 33

4 lobes

Answer 33

1) occipital

2) parietal

3) frontal

4) temporal

note: no single function of the body is concerned with any one individual lobe. they work in tandem. ex: movement is mediated by the frontal and parietal lobes.

Question 34

2 types of cortical connections

Answer 34

1) ascending sensory connections

2) descending motor connections

Question 35

ascending sensory connections

Answer 35

sensory info from the body enters the spinal cord and is then transferred via the thalamus to the somatosensory cortex for processing. smell is the only sense that does not go through the thalamus - it goes directly to the olfactory cortex with no processing. the only thing the thalamus does is tell us whether we like a smell or not.

Question 36

descending motor connections

Answer 36

from the cortex to the spinal cord through the corticospinal tract, and to nuclei within the brainstem. other pathways responsible for higher levels of motor control go to the BG, cerebellum, and the limbic system.

Question 37

association fibres/neurons

Answer 37

connections within the cerebral cortex that occur on the same cerebral hemisphere.

Question 38

commissural neurons

Answer 38

connections within the cerebral cortex between cerebral hemispheres. ex: corpus callosum. these let one side of the brain know what the other is thinking or doing.

Question 39

projection neurons

Answer 39

extend long distances and connect structures from the brain to the spinal cord or vice versa. these include motor fibers that are descending from the cortex to the spinal cord, and ascending somatosensory fibers bringing in info from the spinal cord to the cortex.

Question 40

diffusion tensor tractography (dti)

Answer 40

type of MRI that relies on looking at the ways in which water diffuses through structures. enables us to image myelin so we can plot individual pathways.

Question 41

Cajal & Golgi

Answer 41

won the Nobel prize in physiology and medicine for their discovery that the brain was not a single continuous entity, but composed of individual cellular units.

Question 42

2 major cell types of the NS

Answer 42

1) neurons

2) glia

Question 43

neuronal communication

Answer 43

neurons communicate by passing electrical signals along their elongated form, and they convert it into a chemical signal to activate another electric signal in the next neuronal network.

Question 44

neuronal communication speed

Answer 44

from 1 mph (speed of a tortoise) to 268 mph (faster than most F1 cars).

Question 45

types of neurons

Answer 45

1) classic model neurons: receives signals from and sends signals to other neurons, long extended shape

2) sensory neurons: can be activated by skin cells, for example

3) motor neurons: can stimulate muscle movement

4) interneurons: can send and receive signals with multiple other neurons. they carry info between sensory and motor neurons

Question 46

glial cells

Answer 46

the “glue” of the NS. they support neurons, and have three subtypes:

1) astrocytes

2) oligodendrocytes

3) microglia

Question 47

astrocytes: functions

Answer 47

1) distribute nutrients from the blood supply to neurons

2) ensure the maintenance of extracellular ionic balance

3) tissue repair

4) regulation of synaptic activity by direct contact with synapses

5) astrocyte-astrocyte signaling via gap junctions (gaps in the cell membrane that leak charge ions)

Question 48

microglia: functions

Answer 48

smaller than astrocytes

1) resident immune cells of the brain

2) clear debris

3) recruit other cells to sites of damage

4) aid in tissue repair

5) can also degrade synapses, essential for synaptic pruning, BUT might make matters worse when neurons undergo chronic stress during disease by preventing recovery

Question 49

oligodendrocytes: functions

Answer 49

equivalent to Schwann cells in the PNS

1) support and insulate neuronal axons by generation of myelin sheath

2) increase speed of neuronal signaling through saltatory conduction

3) provide metabolic support

Question 50

neuroinflammation

Answer 50

activation of glia within our NS. this may initially be a defense response to threat to protect neurons, but chronic activation can lead to the over activation of astrocytes and microglia and toxicity to neurons.

Question 51

purkinje cells

Answer 51

highly branches as they receive many inputs and are the only output of the entire cerebellar cortex.

Question 52

axonal length

Answer 52

can vary widely, determining the distance of output in the network. the longest axon in the body is from the lower motor neurons, 1 meter in length.
if the cell body was the size of a ping pong ball, the axon would be 380 meters long, just under 4 football fields in length!

Question 53

dendritic spine

Answer 53

small protrusions on dendrites which form the postsynaptic side of the synapse with axon terminals from other neurons. their shape and size affect how they receive and transmit input: larger surface area spines provide more space capacity for neurotransmitter receptors and from stronger, more stable synapses.

Question 54

microglial morphology

Answer 54

microglia change morphology when they become activated or ‘reactive’, becoming rounder and more phagocytic.
- reactive microglia release more cytokines to attract more microglia to the site of perceived injury
- phagocytic microglia engulf any perceived debris, including synapses

Question 55

microglial scoring system

Answer 55

1: ramified, normal

2: reactive

3: amoeboid

4: phagocytic

this shows progressive inflammation.

Question 56

astrocytosis

Answer 56

an increased number of cells in a given location is due to the local recruitment or enhanced proliferation of astrocytes

Question 57

neuronal substructures

Answer 57

1) nucleus: where all genetic info is stored

2) endoplasmic reticulum: where some new proteins are produced, sorted, and processed for delivery to their required location

3) Golgi apparatus: additional sorting and processing centre

4) mitochondria: energy generator of the cell, also have key roles in calcium buffering and cell signaling

5) lysosome: enzyme filled vesicles for the degradation of proteins and organelles when faulty

6) cell membrane: lipid bilayer containing receptors for cellular communication

Question 58

unique features of a neuron

Answer 58

1) neurons have an unusually high energy demand, the majority of which is used to maintain electrical equilibrium (sodium potassium ATP pump). it also is used for recycling of neurotransmitters and calcium buffering

2) neurons need to transport cargo along long distances due to their extended morphology, as the majority of proteins and mitochondria are produced next to the nucleus but are needed at synapses. cargo is transported along microtubules away from the nucleus (ANTEROGRADE) or towards the nucleus (RETROGRADE).

3) neurons are vulnerable to stress: neurons are post-mitotic, meaning they cannot undergo cell division for growth or repair, making them vulnerable with age as cells deteriorate and have a reduced resistance to cell stress.

Question 59

retrograde transport impairment

Answer 59

could lead to a buildup of dysfunctional components at the synapse and a reduction in the supply of recycled components, blocking normal synaptic function.

Question 60

processes that become dysfunctional with aging

Answer 60

• protein clearance
• DNA repair
• mitochondrial function

Question 61

neuronal plasticity

Answer 61

ability for neurons to adapt to stimuli, such as the growth of existing or new synapses during memory formation

Question 62

renewal of proteins

Answer 62

via protein synthesis (through gene expression) or protein recycling

Question 63

gene expression

Answer 63

the process by which a gene (DNA) is used to synthesize the product it encodes. this is most commonly protein, but can also include functional RNAs such as transfer RNA (tRNA) or ribosomal RNA (rRNA)

Question 64

two steps of gene expression

Answer 64

1) transcription: the photocopying of DNA into messenger RNA (mRNA). This keeps the DNA in the nucleus where it can be protected from damage.

2) translation: the literal translation of the genetic code on the mRNA photocopy into protein

these processes are regulated so that proteins are only made when needed

Question 65

transcription

Answer 65

the enzyme RNA polymerase moves along the DNA, copying its code (A, G, C, T) into mRNA (A, G, C, U). the DNA structure needs to be relaxed for transcription via epigenetic practices, like DNA methylation.

Question 66

RNA splicing

Answer 66

before being exported to the cytoplasm for translation, splicing machinery slices non-coding regions (introns) at the mRNA, only leaving protein coding. alternative splicing can slice different regions, producing different RNA transcripts that encode for different proteins with different functions. this is the way in which the genetic code can increase the number of potential proteins it makes.

Question 67

translation

Answer 67

in the cytoplasm, ribosomes read mRNA code and translate it into protein. the ribosome recognizes a 3-base pair code (1 amino acid; AUG or ATG) and brings in a tRNA carrying the appropriate amino acids. Binding them together, a polypeptide is formed, and once folded, becomes the protein.

Question 68

local translation

Answer 68

though translation usually occurs close to the nucleus, in neurons, it occurs sometimes at sites with high protein demand, such as synapses.

Question 69

protein processing and folding

Answer 69

protein folding occurs as soon as a protein is made, and then undergoes quality control to ensure it is correct. thus, misfolded proteins can be targeted quickly for degradation.
proteins also have post-translational modifications that modulate their folding, such as phosphorylation, greatly increasing the diversity of protein functionality.
protein misfiling is a major cause of neurodegenerative disorders, usually leading to buildup of aggregated protein in the brain.