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NB1 > Neurons And Glia > Flashcards

Neurons And Glia Flashcards

1
Q

Describe the basic structure of neurons

A
  • Dendrites covered in dendritic spines make synaptic connections with other neurons
  • Nissl bodies in the soma contain RNA granules and ribosomes
  • Axons and dendrites are collectively known as neurites
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2
Q

What are neurons?

A

Neurons
• Excitable: Generate and conduct action potentials (APs)
• Main role is signaling – integration, communication

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3
Q

What are Glia?

A

Glia
• Supportive of neurons but also with signalling roles

  • Not excitable in the classic sense (i.e., do not fire APs)
  • But oscillations in intracellular Ca2+ (calcium waves) promote release of gliotransmitters (e.g., glutamate, ATP)
  • Cell types are categorized according to morphology, location and functional properties
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4
Q

What is the signoficance of morphology?

A

Morphology is related to signal reception and transmission: Taking a multipolar neuron, such as a motor neuron as our example, we see the soma expressing with dendrites that may be covered in spines. The primary function of dendrites is to integrate chemical signals emitted from axons (typically from other neurons). The spines, if present, can serve as post-synaptic targets

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5
Q

What are Nissl bodies?

A

Nissl bodies are the histological sign of the rough endoplasmic reticulum, a major site of protein synthesis

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6
Q

Whats the importance of the Axon Hillock (AH)?

A

The axon hillock (AH) is the site of initiation of action potentials. In many neurons, the AH arises from a conical elevation of the soma. The first 50-100 microns of the axon emerging from the AH is the axonal initial segment. Unlike other euokaryotic cells, neurites do not readily support diffusion, so transport mechanisms are required for the sufficient movement of materials throughout the lengths of the axons and dendrites.

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7
Q

What is the purpose of Myelin?

A

Myelin is fused membranes of Schwann cells or oligodendrocytes forming an insulating sheath around axons, which may collateralize extensively

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8
Q

What are Synaptic boutons?

A

Synaptic boutons contain synaptic vesicles with stored neurotransmitter destined to undergo exocytosis. In neurons that release catecholamines, serotonin or peptides there are dense cored vesicles whereas in those like motor neurons that release acetylcholine, the vesicles are clear.

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9
Q

What are the components of the cytoskeleton?

A
  • Microtubules: dimers of  and  tubulin added at the positive end of microtubules = Polymerization (involved in transport)
  • MAPs (microtubule-associated proteins) stabilize microtubules
  • Neurofilaments (NF) number determines axonal diameter

• Microfilaments (MFs) mediate growth cone advance during
growth or repair after injury

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10
Q

What are microtubules in neurons?

A
  • Microtubules
  • Single microtubule is about 100 μm in length, 25 nm in diameter
  • Composed of 13 protofilaments, formed from pairs of α− and β-tubulin
  • Polar structure creates a positive and minus end of the polymer
  • Organized by microtubule-organizing centres (MTOCs, contain γ-tubulin)
  • Stabilized by microtubule-associated proteins (MAPs), e.g. tau proteins
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11
Q

What are neurofilaments?

A

Neurofilaments
• Most common filaments in neurons, diameter 10 nm

  • Very stable with little turnover
  • Create the scaffolding of the cytoskeleton
  • Level of neurofilament gene expression controls axonal diameter
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12
Q

What are microfilaments in neurons?

A
  • Microfilaments
  • Braids of two thin strands of actin filaments, diameter 5 nm
  • Anchored to membrane by mesh just beneath the cell membrane
  • Participate in growth cone advance during neuronal growth or repair
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13
Q

What are the types of axonal transport?

A

Anterograde transport
Kinesin
(microtubule-associated ATPase) moves vesicles along microtubules towards positive end - away from soma

Retrograde transport
Dynein
protein (MAP)-ATPase - towards negative end of microtubules - towards soma

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14
Q

What is the function of kinesin transport proteins?

A
  • ATPase responsible for fast anterograde transport

• Similar to myosin in muscle

• Binding sites for attachment of large structures, e.g., vesicles
and mitochondria

• Movement towards MT positive end, i.e., nerve ending

• Becomes inactivated in nerve ending and carried back to the
soma by retrograde axonal transport to be re-activated

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15
Q

What is the function of Dynein as a transport protein?

A
  • ATPase responsible for fast retrograde transport
  • Also the motor protein for movement of cilia and flagella
  • Movement towards MT negative end, i.e., soma
  • Inactivated in soma, activated again in nerve ending
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16
Q

What are the possible speeds for a anterpgrade transport (kinesin driven)?

A

Fast (100-500)- transports Vesicles, Mitochondria

Slow (1-10) - transports Soluble proteins (calmodulin) and enzymes

Slow (0.1-1.0)- transports Cytoskeletal molecules (Tubulin, Actin, NF protein)

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17
Q

What are the speeds oand contents of dynein transport?

A

Fast (200-300)
Lysosomes, enzymes, recycled vesicular membranes, NGF
Viruses: Herpes, Rabies

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18
Q

Describe transport along dendrites

A

Transportalongdendrites
• Axonic microtubules always have negative end towards
soma and positive end distally

  • Dendritic microtubules are of mixed orientation
  • Half with +ve ends facing soma, other half opposite

• This may selectively direct movement of some materials
to dendrites rather than down axon

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19
Q

Summarize axoplasmic transport

A

Axoplasmicflow
• Continuous movement of axoplasm along axons
• ~ 1 mm/day
• Slower than axonal transport and does not explain
axonal movement rates for proteins and organelles

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20
Q

Where is axoplasmic flow occur?

A

Axoplasmic Flow Occurs in Peripheral Nerve Axons

Continuous movement of axoplasm occurs along axons at a rate of about 1 mm/day, but this transport does not account for the observed transport rates of proteins and organelles within axons. Faster axonal transport processes occur

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21
Q

What rate does axonal. Transport occur at in lysosomes?

A

Retrograde transport for lysosomes and endolysosmes degrade endocytosed material and redundant cellular components are degraded. These materials are packaged in large membrane-bound organelles that are part of the lysosomal system.

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22
Q

What type of transport do viruses use?

A

Retrograde Axonal Transport: Some viruses use retrograde transport to infect neurons. Examples are the herpes virus and the rabies virus which gain access to neuronal cell bodies by entry into axons in the skin. The rabies virus replicates well in the cell body, destroying his host cell and then passing to nearby neurons to continue its devastating work.

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23
Q

What is the significance of axonal transport to neurons?

A

Without fast axonal transport, the soma and nerve ending would be unable to exchange materials at a satisfactory rate to retain the viability of the distant endings of the neuron. By contrast, the neuron’s electrical signalling ability is fast over the same distance. Even at the slowest conduction velocity of the action potential, this electrical signal is transferred at a rate of about 0.5 m/s (i.e., about 100,000 faster than the fastest rate of axonal transport).

Interruption of axonal transport leads to death of axons distal to the site of injury in a process called Wallerian degeneration occurs, likely in relation to disrupted axonal transport mechanisms. In Alzheimer’s disease, the microtubule-associated protein Tau is deranged, leading to the intracellular formation of neurofibrillary tangles, thereby disrupting microtubular structure and axonal transport.

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24
Q

How are neurons classified by neurites?

A

One way to classify a neuron is by its total number of neurites. One class of neurite is the dendrite and the other is the axon. Most neurons have several dendrites and only one axon (which may collateralize). The morphological types are pseudo-unipolar, bipolar and multipolar, the names relating to the pattern of neurites extending from their cell bodies.

Single neurite = unipolar, two = bipolar, three or more = multipolar

25
Q

What type of neurons are most prevelant in the brain and soinal cord?

A

Most neurons in the brain are multipolar. Motor neurons in the spinal ventral and lateral horns of the SC, autonomic ganglion cells. Mostly inhibitory in the CNS and referred to as Golgi type II. Multipolar neurons with long axons are called Golgi Type I; multipolar neurons with short axons are often inhibitory and are called Golgi Type II.

Bipolar- retinal sensory, olfactory and inner ear. Have two processes one axon and one dendrite

26
Q

Where are psuedo-unipolar neurons located?

A

Pseudo-unipolar spinal sensory neurons have one process, which divides into a central branch and a peripheral branch. Each branch has structural and functional characteristics of an axon. They are called pseudo-unipolar because they are originally bipolar. The two processes fuse during development to form a single process that bifurcates at a distance from cell body.

These are peripheral sensory neurons, the cell bodies of which aggregate to form spinal and cranial nerve ganglia

27
Q

What are the functional classifications of neurons?

A

Afferent (eg sensory) From PNS to CNS

Efferent (eg motor) From CNS to PNS

 Interneurons Connect and modulate input-output of Afferent and Efferent neurons in CNS and PNS
28
Q

What are the characteristics of axons by myelination and diameter?

A

Axons are commonly myelinated
• Myelination speeds axonal conduction of action potentials and
reduces energy needs for concentration gradients

  • Neurons can be grouped or categorized according to their axonal diameter and myelination
  • Both correlate with conduction velocity
  • Class I: largest and most rapidly conducting fibres
  • Classes II and III: intermediate diameter
  • Class IV: unmyelinated and smallest diamete
29
Q

Contrast excitatory and Inhibitory neurons

A

Excitatory Neurons
• Cause post-synaptic excitation
(depolarization)

  • Inhibitory Neurons
  • Cause post-synaptic inhibition (hyperpolarization)
  • Transmitter effect depends on post-synaptic receptors
  • e.g., dopamine D1 family coupled to Gsα → ↑[cAMP]
  • vs. dopamine D2 family coupled to Giα→[cAMP]
30
Q

Not uncommonly, neurons are described as either excitatory or inhibitory.

A

Not uncommonly, neurons are described as either excitatory or inhibitory. Transmitter released by excitatory neurons tends to depolarize membranes of other neurons; transmitter released by inhibitory neurons tend to polarize or stabilize membranes of other neurons. It is noteworthy, however, that receptors (not transmitters) ultimately dictate excitatory versus inhibitory effects of transmitters (or the neurons from which the transmitters are released).

31
Q

What are the key roles of neuroglia?

A

Glia = Greek for glue
• Glial cells outnumber neurons in the nervous system

• Key roles:
• Maintaining the ionic milieu of nerve cells
• Modulating the rate of nerve signal propagation (myelination)
• Modulating synaptic activity by controlling the uptake of the
neurotransmitters at or near the synaptic cleft
• Providing a scaffold for neural development (radial glia)
• Participating in recovery from neural injury

32
Q

What are the main types of neuroglia?

A 
Four main types in CNS:
 • Astrocytes
• Oligodendrocytes 
• Microglia
• Ependymal cells
33
Q

What are astrocytes?

A
  • Restricted to brain and spinal cord (CNS)

* Most common CNS glial cell type

34
Q

What are the key functions of astrocytes?

A
  • Component of blood-brain barrier
  • Scar formation
  • Regulate chemical content of extracellular space
  • Limit spread of neurotransmitter from synapses
  • Uptake of neurotransmitters after release from nerve terminals
  • Recycling neurotransmitters such as Glu, GABA
  • Uptake of excess K+ released following APs
  • Disperse K+ throughout a greater volume: spatial buffering
35
Q

Describe in depth what is the relevance of astrocytes

A

Astrocytes: restricted to brain and SC; largest of glial cells, have elaborate local processes that give the cells star-like appearance (hence the prefix astro), function is to maintain in a variety of ways an appropriate chemical environment for neural signaling as explained in the following slides. Astrocytes provide support for neurons: 1- a barrier against the spread of NT from synapses, uptake of NTs after release from nerve terminals such as glutamate, GABA, where they are processed for recycling. Uptake of excess K released following nerve impulses in the EC space. Astrocytes take up K via membrane pumps and transporters and dissipate it over a wider area as they have an extensive network of processes. Astrocytes are also connected via gap junctions, which can assist further in K spatial buffering.

36
Q

What is the significance of astrocytes in K+ regulation?

A
  • [K+]O increases after impulse propagation in neurons
  • High [K+]O interferes with AP generation
  • Excess K+ is taken into astrocytes via
  • Na/K ATPase
  • Na/K/Cl- co-transporter (NKCC)

Spatial Buffering
• Astrocytes then distribute K+ throughout a greater volume

• Range enhanced by gap junctions between astrocytes

37
Q

Why are astrocytes needed for potassium regulation?

A

Neuronal activity tends to raise [K+]o in the extracellular fluid and, if a significant rise occurs, it will interfere with neuronal signaling by depolarizing neurons (as described in the lectures on Resting and Stimulated Excitable Cells). Astrocytes have large numbers of open K+ ion channels facilitating removal of K+ ions from the extracellular fluid. Potassium ions taken up at one region of the cell are distributed throughout the cytoplasm of the cell and into neighbouring cells via gap junctions.

This sharing of the K+ ion load is called K spatial buffering. (Bear Fig 3.20 p 71). High [K]o interferes with impulse generation as we’ll see next lecture (resting excitable cells, and stimulated excitable cells).

38
Q

What are the main soyrce of energy neuronal support?

A

Main source of neuronal energy is circulating glucose

  • Astrocytes store glycogen and supply neurons with lactate
    • Alternative energy source for ATP generation
    • Exhausted within ~10 min
39
Q

What is the purpose of strocytes for energy support?

A

Astrocytes store Glycogen and Supply Neurons with Lactate

  • In the CNS, astrocytes are the main storage depot for glycogen which can be converted to lactate and transferred to neurons as an alternative source for ATP production. Neurons pick up lactate from ECF via the transporter protein MCT2 and use it to generate energy in the form of ATP molecules.
  • If blood supply is interrupted, the normal supply of glucose to the CNS will be terminated. Neuronal activity can survive this loss but only until the glycogen is used up (within about 10 minutes of blood supply interruption).
40
Q

What are microglia?

A

• CNS macrophages

• Smaller than
astrocytes/neurons

41
Q

What are the key functions of microglia?

A 
Key functions:
• Phagocytosis
• Removal of debris
• Synaptic pruning
Immune activation
• Produce pro-inflammatory cytokines during neuronal injury
42
Q

What are the 2 main sites of microglia?

A

Two main states

  • Resting/surveillance: extensive branching processes
  • Activated: rounded, possibly with phagocytic inclusions
43
Q

What is the origin of microglia and the significance of this?

A

Microglial cells: Derived primarily from hematopoietic precursor cells rather than ectodermal cells (although some may be derived directly from neural precursors).

They share many properties with macrophages found in other tissues and may be classified as such. They are primarily scavenger cells that remove the cellular debris from the site of injury. Additionally, they secrete signaling molecules (cytokines) that can modulate local inflammation and influence the survival or death of cells. Following brain injury, the number of microglia increases dramatically.

Some proliferate from microglia resident in the brain, while others come from cells that migrate to the site of injury and enter the brain via local disruption of cerebral vasculature

44
Q

What is the impact of microglia on the entire body?

A

Microglia are constantly moving and analyzing the CNS for damaged neurons, plaques, and infectious agents. The brain and spine are considered “immune privileged” organs in that they are separated from the rest of the body by a series of endothelial cells and astrocytes, which prevents most infections from reaching the otherwise vulnerable nervous tissue. In the case where infectious agents are directly introduced to the brain or cross the blood-brain barrier, microglia must react quickly to increase inflammation and destroy the infectious agents before they damage the sensitive neural tissue. Due to the unavailability of antibodies from the rest of the body (antibodies are too large to cross the BBB), microglia must be able to recognize foreign bodies, swallow them, and act as antigen-presenting cells activating T-cells. Since this process must be done quickly to prevent potentially fatal damage, microglia are extremely sensitive to even small pathological changes in the CNS. They achieve this sensitivity in part by having unique potassium channels that respond to even small changes in extracellular potassium. When the CNS is injured, microglia become enlarged, mobile and phagocytic. Inflammatory events in the central nervous system (CNS) contribute to the disease process in Multiple Sclerosis (MS), Alzheimer ́s Disease (AD), and Spinal Cord Injury (SCI), and activated macrophages/microglia are central to this response. Immunological activation of these cells leads to the production of a wide array of cytokines, chemokines, matrix metalloproteinases and neurotoxins and ultimately to glial/neuronal injury and death.

45
Q

Where are myelinated glia located?

A
  • Oligodendrocytes are found in the CNS
  • Schwann cells are the myelinating glia of the PNS

• Myelination provided by flattened cytoplasm, wraps up
to 100 membrane/myelin layers around axons

• Interrupted by nodes of Ranvier (1m) every 1000 μm

46
Q

What do oligodendrocytes do?

A

Oligodendrocytes: In the CNS, oligodendrocytes wrap their membranes around long segments of axons to lay down a layer of myelin composed of up to about 100 membrane layers. The myelin acts as an electrical insulator and reduces capacitance of the axonal membrane and thereby elevates conduction velocities of impulses.

The small regions (1 micrometer) of unmyelinated membrane between adjacent myelinated segments are called the Nodes of Ranvier. Oligodendrocytes myelinate several segments on the same axon and segments of several axons in its vicinity. Each myelinated segment is about 1000 μm long.

47
Q

What do Schwann cells do?

A

Schwann Cells: In the PNS, Schwann cells myelinate axons. Each Schwann cell myelinates only one segment of an axon. So, each myelinated peripheral axon is insulated by a large population of Schwann cells. During myelination in the PNS, Shwann cells rotate around the axon.

48
Q

What do Schwann cells do for severed axons?

A

Schwann Cells Facilitate Regeneration of Severed Axons

When an axon is cut in a peripheral nerve, Schwann cells retract from the isolated distal axonal segment, increase in number and form a guide tube.

They also secrete growth factor to induce axonal growth of the proximal axonal segment along the guide tube to its target cell.

The Axon Instructs the Schwann Cell to Myelinate It
The axon destined to become myelinated sends an appropriate signal to the Schwann cell to induce wrapping and myelination.

Small diameter axons introduced experimentally to Schwann cells do not induce them to form myelin.

49
Q

What are the types of Ependymal cells?

A

Originate from ventricular zone in the neural tube

  • Two types
  • Choroidal Ep cells in choroid plexus: CSF secretion
    * Tight junctions: CSF components must pass trans-cellular

• Extra-choroidal ependymal cells (ependymocytes)
• Ciliated ependymal cells(liningventricularsystem)
• Propel CSF through ventricles and spinal cord
• Gap junctions for exchange between CSF and interstitial
fluid

50
Q

What are the differences between differeng types of ependymal cells ?

A

Other non-neuronal cells exist in the brain, such as ependymal cells (modified ep cells), which provide the lining of the fluid-filled ventricles. There are two types of ependymal cells, namely group 1 choroidal epithelial cells of the choroid plexus and group 2 extra-choroidal ependymal cells. Group 1 cells are joined by tight junctions excluding passage of water and solutes by the paracellular route across the choroid plexus, forming the blood-CSF barrier. Group 2 cells (ependymocytes) line the ventricles of the brain and central canal of the spinal cord and are in contact with the cerebrospinal fluid (CSF). They are joined together by gap junctions (not by tight junctions).

51
Q

Where are Group 1 ependymal cells located?

A

Group 1. These cells are the secretory cells of the Choroid Plexus. Virtually all of the solutes and water molecules that pass from blood to CSF via the choroid plexus must pass through the cytoplasm of these cells (transcellular route).

52
Q

Where are Group 2 ependymal cells located?

A

Group 2. These cells are ciliated and line the brain’s ventricles and spinal cord canal. They assist with propelling & circulation of CSF within CNS. Moreover, solutes and water may pass readily around the cells via the paracellular route. This permeable route allows effective exchange between CSF and interstitial fluid.

53
Q

Describe the regeneration and degeneration of axons

A
  • Wallerian degeneration distal to axonal transection
  • Proximal segment may form sprouts
  • Schwann cells proliferate:
  • Forming a guide tube
  • Release nerve growth factors
  • Re-myelinate the regenerating axon (growth ~2 mm/day)
54
Q

Describe regeneration and degeneration in the CNS

A

• Oligodendrocytes and astrocytes inhibit axonal regeneration

• Do not form guide tubes like
Schwann cells

  • Nogo protein blocks axon growth
  • Alzheimer’s disease features derangement of Tau protein
55
Q

Describe regeneration process of axons in PNS

A

Regeneration of Axons in the PNS
• Following axonal transection

  • Distal axonal segment degenerates
  • Proximal axonal segment may form sprouts
  • Schwann cells
  • Proliferate, forming a guide tube
  • Release nerve growth factors, encouraging axonal regeneration
  • Re-myelinate the regenerating axon (axons grow at a rate of about 2 mm/day)
  • Target cells may die unless reinnervated

Chromatolysis reflects post-traumatic neuronal swelling and dilution of organelles.
Anterograde degeneration reflects the transsynaptic death of the denervated (postsynaptic) cell. Retrograde degeneration reflects the death of the presynaptic cell.
Regeneration of transected CNS axons is currently clinically untenable. Central glial cells do not secrete significant amounts of nerve growth factor. Oligodendrocytes do not form guide tubes as do the Schwann cells in the PNS. They secrete ‘Nogo’ protein which inhibits axonal growth. Moreover, gliotic scars block axonal regrowth.

56
Q

What is Multiple Sclerosis?

A

Multiple Sclerosis
• Autoimmune demyelinating disease of the CNS
• Blurring, partial loss of vision – CNII
• Muscle weakness - corticospinal tracts
• Incoordination - cerebellum

57
Q

What is Guillain-Barré Syndrome?

A

Guillain-Barré syndrome

  • Inflammatory demyelinating disease of the PNS
  • Affects myelin sheath and axons
  • Symmetrical ascending paralysis
58
Q

How much tumors of glial origin are brain tumors vs spinal tumors?

A

Tumors of glial origin

• ~ 50% brain tumors and 25% of spinal tumors

NB1 (67 decks)

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