Lecture 2: Neuron Doctrine Flashcards

1
Q

What is the reticulum debate?

A

do brain cells join together as one, or just touch processes

  • discrete cells vs. reticulum
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2
Q

What is a neurite?

A

long, thin projection emerging from cell body of neuron

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3
Q

Why was there a debate about discrete cells vs. reticulum?

A

with such narrow processes, even when using light microscopy, it’s hard to tell whether the cell plasma membranes join (ie. fuse together) or just touch

biggest debate in Neuroscience (in 1895) was about what could be seen in Golgi stains

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4
Q

What is the answer to the reticulum debate? Who resolved the debate?

A

resolved (by Cajal) – brain does consist of individual cells which touch, but don’t join

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5
Q

Where did Cajal’s observations to resolve the reticulum debate come from?

A

observations and evidence from Golgi’s ‘black stain’

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6
Q

What is Cajal’s evidence for resolving the reticulum debate? (3)

A
  • specialized terminal ‘blobs’ (swellings) – occur wherever neurites touch
  • or​​ganized subcellular fibril structures are continuous within a cell body and its neurites, but discontinuous where two neurites meet
  • neurites are longer in later developmental stages and after longer periods following damage/regrowth
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7
Q

What confirmed Cajal’s powers of observation for the reticulum debate?

A

transmission electron microscopy

  • where two neurites come closest, there is still a gap (~10s of nm) between the membrane of one neurite and another
  • where two neurites come closest, there are usually asymmetric neurite and membrane specializations
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8
Q

How did transmission electron microscopy confirm the solution to the reticulum debate?

A

(smaller wavelengths = higher resolution) made it possible to see neurites that meet retain separate membranes

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9
Q

What are the 4 points of the Neuron Doctrine (Cajal’s evidence)?

A
  1. nervous system is composed of distinct, discrete units
  2. basic unit of the nervous system is the individual cell, or neuron
  3. information (ie. electrical signals) flows within a neuron from dendrite to axon
  4. information flows between cells from axon terminals across synapses to dendrite/soma of next cell
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10
Q

Neuron Doctrine (Cajal’s Evidence)

  1. Nervous system is composed of distinct, discrete units
  2. Basic unit of the nervous system is the individual cell, or neuron

What (two) consequences does this have for how all these individual, elongated cells are going to perform the functions of the nervous system as a whole?

A

neurons need a means of encoding and relaying information along neurites
- even during Golgi/Cajal reticulum debate, it had been long known that nervous system was source of ‘animal electricity’ which was necessary to its function – no one knew how

neurons also need a means of passing information across gaps between cells

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11
Q

What are neurites?

A

electrical ‘cables’

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12
Q

What are some characteristics of neurites?

A
  • long
  • high surface area
  • low internal resistance
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13
Q

How did Cajal predict that neurites are electrical ‘cables’?

A

based on their structure

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14
Q

What are neurites specialized to do?

A

specialized for rapidly generating, integrating and transmitting electrical signals via cell membrane

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15
Q

What are proteins in the cell membrane specialized to do?

A

specialized to be able to rapidly alter membrane’s electrical potential

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16
Q

What are the 2 types of neurites for typical neurons?

A

dendrites OR axons – each have distinct properties

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17
Q

How many axons and dendrites does a neuron have?

A

has only one axon, but can have more than one dendrite

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18
Q

Do axons or dendrites have many sub-brances?

A

both

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19
Q

What is a neuronal compartment?

A

term that recognizes somata and axon terminals, which also have distinct anatomy and functions and are not actually neurites

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20
Q

What are the 4 distinct neuronal compartments?

A
  • dendrites
  • cell body/soma
  • axon
  • axon terminals
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21
Q

Where is most of the length of long neurons?

A

in the axon

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22
Q

What do discrete cells require a specialized means for? What is this specialized means?

A

intercellular communication (to pass information) – synapse

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23
Q

What is a synapse?

A

location where two neurons make contact and are able to pass physiological information from one cell to another

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24
Q

How did Cajal know in what direction the signals flowed through a neuron?

A

observed olfactory organ

  • nose is a sensory organ
  • can determine things based on where the dendrites are in the nose
  • nose will more often be bringing information in
  • dendrites are in CNS (receiving end)
  • axon is leaving to target muscle
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25
Q

How and where does information flow through neurons?

A

predominantly unidirectionally, from dendrite to axon to next cell (across synapses)

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26
Q

What happens to information flow between neurons?

A

synapses transfer information from presynaptic cell to postsynaptic cell

  • from axon terminal to dendrite
  • from axon terminal to soma
  • from axon terminal to another axon terminal
  • sometimes (rarely) they also occur between dendrites
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27
Q

Synapse Debate: What are the two options of how synapses work?

A
  • electrical synapses

- chemical synapses

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28
Q

What is an electrical synapse?

A

specialized electrical ‘junctions’ at membrane that allow flow of current from one neuron directly into another

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29
Q

What is a chemical synapse?

A

no direct opening between neural membranes – chemical messenger diffuses across gap (synaptic cleft) between neurons

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30
Q

What is the synapse rule in most nervous systems (especially vertebrates)?

A

chemical synapses

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31
Q

How do the majority of synapses in the vertebrate nervous system communicate?

A

communicate across synaptic clefts by release of neurotransmitter chemicals from axon terminals

  • neurotransmitters trigger new electrical signals in dendrites (or other structure) on other side of synapse
  • electrical synapses (mediated by gap junctions) also occur – but not as common
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32
Q

TRADE-OFF: Fully electrical signalling would be faster (and more energetically efficient) – what are the advantages of chemical signalling? (3)

A
  • amplification of signals – ie. small axon terminal can depolarize a large somata
  • modification of the transfer function (plasticity) – size of the effect the presynaptic neuron has on postsynaptic neuron can be altered
  • computation processing (signal inversion) – chemical signals can be excitatory OR inhibitory
33
Q

What are the 2 methods of solving the chemical/electrical synapse debate?

A
  • electron microscopy

- physiology experiments

34
Q

How is electron microscopy a method of solving the chemical/electrical synapse debate?

A

can show that electrical synapses are rarer than chemical synapses by counting how often you see the different structures necessary for each type of synapse

35
Q

How are physiology experiments a method of solving the chemical/electrical synapse debate?

A

neurobiologists resolved the debate years before synapses were visualized using EM through use of clever experimental design

36
Q

Nobel Prize-worthy demonstration of chemical synaptic transmission used frog hearts. In 1921, what did researchers already know?

A
  • electrically stimulating nerves could also drive (or inhibit) muscle contractions, including in the heart
  • adding certain organic chemicals to muscles could make them contract (or sometimes, stop contracting)
37
Q

What is the simplest definition of neuron types based on?

A

connectivity – three categories

defined by the cell types which the neuron contacts, and directionality of those synapses

ie. is the neuron bringing information into the nervous system, passing information within the nervous system, or bringing information out to non-neuronal cells

38
Q

What are the 3 categories of neurons based on connectivity?

A
  • sensory neurons
  • interneurons
  • motor/effector neurons
39
Q

Sensory Neurons

A
  • dendrites in body, axon going into nervous system
  • brings sensory information from outside of nervous system into the system
  • makes synapses on neurons
40
Q

Interneurons

A
  • connects between neurons
  • only talks to other neurons
  • receives and makes synapses on neurons
41
Q

Motor/Effector Neurons

A
  • brings sensory information out of nervous system
  • receives input from neurons
  • only makes outputs to cells that are not neurons
42
Q

What are other methods of defining neurons? (4)

A
  • structural diversity: number and arrangement of neurites
  • chemical diversity: neurotransmitters released and detected by receptors
  • electrical diversity: speed and/or precision of signals
  • wiring diversity: which other cells are contacted with synapses
43
Q

What is the single cell sequencing (sc-Seq) method?

A

physically separates piece of brain tissue into individual cells, then sequences the RNA from each cell individually, then looks for shared RNA profiles

44
Q

Could there be more than 50,000 types of neurons? Are all those ’50,000’ types actually meaningful?

A

too many to say anything meaningful about the brain

45
Q

TRADE-OFF: Neurons need to be big. Why? What is the challenge of this?

A

neurons have to be big to signal as rapidly as they do (one end of your body to the other), but this makes them exponentially more difficult to get fuel and supplies all the way to the tips of neurites

46
Q

What are some challenges that neurons face? (4)

A
  • size (and transport)
  • creating and maintaining compartment polarization
  • energy intensive, metabolically expensive signalling
  • crossing between biophysics (electrical signalling) and biochemistry (chemical signalling, inside and outside the cell) in a rapid and yet reliable manner
47
Q

How do neurons face challenges?

A

nervous systems come with biological ‘pit crew’ – variety of distinct types of support cells (glia), which are there to keep neurons functioning at peak performance in many different ways

48
Q

What are glia (glial cells)?

A

‘glue’ that hold nervous system together and keep it running

49
Q

What are the 3 types of glia (glial cells)?

A
  • astrocytes
  • myelinating cells
  • microglia
  • ependymal cells
50
Q

How common are glia in the CNS?

A

glia make up ~50% of cells in CNS – but this varies by species and region

although textbooks usually tell you that glia make up ~90% of cells in the brain, recent evidence shows that it is actually more like 50% on average

51
Q

What is the isotropic fractionation method?

A

the approach essentially brains through a high-tech blender, which breaks tissue connections but effectively keeps individual cells intact and alive so that they can be precisely counted by cell-sorting machines

these sorting machines separate isolated cells based on the cell surface proteins they express

52
Q

What is the overall % of glial cells in the brain?

A

ranges from ~33-67% depending on species (~50% in humans)

53
Q

Where are glial percentages/ratios lowest in mammalian species’ brains?

A

lowest in cerebellum, and generally lower in cerebral cortex than other parts of brain

54
Q

Ependymal Cells

Where are they located?

A

ventricle wall and choroid plexus within brain and spinal cord – line CNS ventricles

55
Q

Ependymal Cells

What specialized structure do these cells have? Why?

A

have their own, more permissive form of the blood (CSF) barrier, which allows ependymal cells and choroid plexus to constantly secrete water and ions

56
Q

Ependymal Cells

What is the function of these cells?

A

secrete most of the fluid that becomes CSF

because of glymphatic system, this is also the extracellular fluid (ECF) that surrounds neurons (and can also be called ISF – interstitial fluid)

57
Q

Myelinating Cells

What are they called in the CNS?

A

oligodendrocytes

58
Q

Myelinating Cells

What are they called in the PNS?

A

Schwann cells

59
Q

Myelinating Cells

Why do they have different names in CNS vs. PNS?

A

because they have distinct embryonic origins and different relationships with neurons

60
Q

Myelinating Cells

What is the function?

A

create myelin sheaths that surround some (not all) axons, which provides electrical insulation that speeds conduction of neural signals along axons, and supplies axons with nutrients and trophic factors

61
Q

Myelinating Cells

What part of neurons do these cells contact?

A

only contact axons (NOT dendrites and cell bodies)

62
Q

What is myelin?

A

lipid-rich substance produced inside myelinating glia

63
Q

Where is myelin?

A

concentrated inside the processes of these cells that are wrapped many times around axons

64
Q

Myelin is responsible for the appearance of what?

A

responsible for ‘white’ appearance of ‘white matter’ in nervous system – this occurs anywhere there are high proportions of axons (nerves and tracts)

65
Q

What are microglia?

A

primary immune cells of central nervous system – specialized macrophage-related cells that reside within CNS

66
Q

Microglia

When do they enter the CNS?

A

mostly enter during early development, but can cross BBB under specific circumstances

67
Q

The brain is immunoprivileged. What does this mean?

A

most WBCs that make up immune system cannot enter brain because of BBB

68
Q

What do activated microglia do?

A

activated microglia are mobile, and move by rearranging their cytoskeleton

69
Q

Microglia

What is their function?

A

perform typical innate immune functions (surveillance, scavenging of invaders, mediating inflammation), and participate in certain forms of neuron/neurite plasticity, or remodelling

70
Q

What is the most common and most diverse glial cell type in CNS, and the ancestors of neurons?

A

astrocytes

71
Q

Astrocytes

What specialized structure do these cells have? What do these structures do?

A

possess cell processes (like neurites but thinner and expressing different proteins)

  • some processes interact with synapses
  • some processes (end-feet) interact with blood vessels and BBB
72
Q

What are satellite cells?

A

act like astrocytes in PNS

73
Q

Astrocytes

What is their function?

A

regulate environment of active neurons – support neural transmission and neuron metabolism in many ways

  • recycling neurotransmitters, and buffering extracellular ions and nutrients/metabolites
  • altering blood vessel diameter and maintaining tight junctions of BBB
  • synaptic and neuron growth and connectivity
74
Q

What are neurons?

A

individual cells

75
Q

How do neurons perform their function?

A

by communicating with each other across gaps between them (principally by chemical messengers)

76
Q

What do common anatomical and physiological features of neurons do?

A

make them specialized for information transfer within the internal components and between them, despite the energetic and development costs this puts them under

77
Q

What does the diversity of neurons allow them to do?

A

allows them to make diverse types of computations on information they pass amongst each other, but poses metabolic and developmental challenges

78
Q

What are glia?

A

diverse group of non-neuronal cell types within nervous system that provide support in various ways to keep neurons functioning