Cells of the Nervous System Flashcards
What stain did early work looking at the structure of the brain use and what did this allow to be seen?
The Nissl stain which only allowed the cell body to be seen
What stain was developed and by who that allowed visualisation of the cell processes?
Golgi’s silver stain
What are the cell processes?
Dendrites and axons
What was Golgi’s reticular theory?
Golgi believed that neurites were fused together to form a reticular network
What is Cajal’s neuron doctrine?
Each neuron is a discrete cell
What is Cajal’s principle of dynamic polarisation?
that neurons transmit information in a particular direction
What is Cajal’s principle of connectional specificity?
he thought that the connections in the nervous system weren’t random (particular types of neurons connected with each-other)
How was Cajal’s theory proved right over Golgi’s?
through the development of the electron microscope
When was the electron microscope developed?
1950s
What is the human eye resolution, light microscope resolution and electron microscope resolution?
- Human eye resolution 0.1mm
- Light microscope resolution 0.1 um
- Electron microscope resolution 0.1nm
What are the advantages of the electron microscope?
- it can examine cell ultrastructure (confirmed the existence of synapses)
What is the disadvantage of the electron microscope?
The cells have to be fixed (dead)
How does immunofluorescence imaging work?
- Prepare selective antibody (or drug) tagged with fluorescent label
- Add to tissue and allow to bind strongly
- Target protein in tissue labelled with antibody
- Wash off any free labelled antibody (or drug)
- Image distribution of fluorescence (which labels antibody distribution)
How do confocal microscopes work?
- Focus a laser at different levels in a tissue that has been labelled with a fluroscent probe
- Use high sensitivity camera
- Imaging software
- You can build up a 3D image of specific cells
What are the advantages and disadvantages of confocal microscopes?
- Advantages:
- You can do this in live cells
- You can examine the physiology of cells
- Disadvantage: modest resolution, 0.1um
What is the Brainbow technique?
- Involves genetically modifying an animal so it’s cells produce random combination of dyes
- You can used it to trace the pathway of individual neurons as they will be stained with colour
What does the Clarity technique do?
- Makes brains transparent so that staining can show vastly more detail
- You need to remove the lipid bilayer using a hydrogel mesh
In the central nervous system what do glial cells do after brain injuries?
they proliferate (multiply) and this can inhibit the regeneration of damaged axons.
What do glial cells do after injury in the peripheral nervous system?
seem to promote the regrowth of neurons
What is the main role of the glia?
To act as a supporting cell
What is the original idea behind glial cells?
that glial cells ‘glued’ neurons together
What’s the glia: neuron ratio?
Outnumber neurons in some brain regions (e.g. 17:1 in thalamus; 1:1 in the cerebral cortex)
Can glial cells divide?
yes - unlike neurons
What are the different types of glial cell?
- Ependymal cells
- Oligodendrocytes
- Satellite cells (won’t worry about them)
- Astrocytes
- Microglia
- Schwann cells
Give features of astrocytes
- Majority of glia
- Star-shaped (their name means star-shaped)
- Fill space between neurons
- Regulate composition of extracellular fluid
- Astrocytes can play an important role in directing the proliferation and differentiation of neural stem cells
Give features of Oligodendrocytes and Schwann cells
- Myelinate axons of neurons
- Oligodendrocytes = CNS, provide insulation for many different axons
- Schwann cells = PNS, only insulates a single axon
Give features of Microglia
- Act as the brain scavengers
- Phagocytic/immune function
- They can migrate
Give features of Ependymal cells
- Ependymal cells line ventricles and also direct cell migration during development of the brain
- Produce CSF
- Recent research says they might be able to turn into neurons – reserve of cells for regeneration?
What type of disorder is Huntington’s disease?
a neurodegenerative disorder that develops between the age of 30 and 50
What are the symptoms and life expectancy of HD (Huntington’s disease)?
- People with HD initially show changes in personality and have problems with cognition. As the disease progresses, they start to experience random jerky movements
- The physical problems and cognitive impairments become worse over time and patients will develop dementia and exhibit rigidity and writhing movements
- Life expectancy after diagnosis is around 20 years
Why would Huntington’s occur?
- HD is an autosomal (chromosome that is not a sex chromosome) dominant disorder due to a genetic abnormality in the huntingtin gene. A section of this gene codes for a repeated sequence of glutamine residues and it’s the number of repeats of the glutamine codon that determines whether the disease will develop or not
- The single letter amino acid code for glutamine is Q, so this region is known as the polyQ region.
- If the repeat count in the polyQ region is less than 27 there is no risk of HD, if it is greater than 40 then the person will get HD, if it is in the range 36-39 then the disease may occur, repeats in the 27-35 range are unstable during cell replication and this can result in further copies being added. The risk of polyQ expansion means that a HD may occur in the offspring of a person who does not themselves develop the disease
What produces the symptoms of Huntington’s?
The mutant version of the protein the huntingtin gene codes for is not broken down correctly by cells and the result is that fragments of the protein (huntingtin) accumulate in neurons as inclusion bodies. Eventually the build up of huntingtin breakdown products will kill the cell.
What is one of the worst affected regions of the brain by Huntington’s?
The basal ganglia (a region of the brain which is vital in the control of movement and is also affected by Parkinson’s)
What happens to astrocytes and microglia due to Huntington’s?
Astrocytes and microglia also undergo changes due to Huntington’s and these changes are associated with neuroinflammation. This neuroinflammation is thought to contribute to neuronal death
What type of disorder is Alzheimer’s disease?
A protein accumulation neurodegenerative disorder that tends to affect people over the age of 65
What are the symptoms of Alzheimer’s?
It produces progressive cognitive decline, with memory problems being an early symptom. Then they sufferers may have problems with language processing, behaviour and will be unable to perform day-to-day tasks
What are the two types of protein deposits with Alzheimer’s?
- Amyloid plaques
- Tau protein
What happens with Amyloid plaques in Alzheimer’s?
- Formed from a protein called amyloid beta
- Amyloid beta is formed with a protein called amyloid precursor is cleaved
- Normally amyloid beta is soluble and problem free
- However, it can sometimes misfold and form insoluble plaques around neurons
- Beta amyloid plaques are toxic to neurones
What happens with Tau protein in Alzheimer’s?
- Element of the cytoskeleton
- Involves in transporting cargos up and down axonal microtubules
- When tau becomes heavily phosphorylated (hyperphosphorylated) it clumps together to form neurofibrillary tangles inside the neuron.
- This disrupts the normal movement of cargo in the neuron and can also result in neuronal death
What happens with Astrocytes and glia in Alzheimer’s?
- they both become active and induce neuroinflammation
- They both attach themselves to amyloid plaques and there is a correlation between the number of activated cells and disease progression
- It’s not clear whether astrocytes are trying to remove plaques or contributing to their build up
- It has been found that astrocytes reacting against plaques lose some of their ability to support neurones and may even start to become neurotoxic
What is a nerve?
bundle of axons that arise from different neurons
What is another name for an axon?
nerve fibre
What is the neuronal structure?
- Cell body with cytosol and organelles including a nucleus
- Cell membrane
- Two types of processes (together called neurites):
Dendrites (come out in tree like structure around the cell body) specialised for receipt of information
Axons (emerge from neurons axon hilluc) specialised for transmission of information
What are unique(ish) features of neuronal cells?
- they can’t divide
- they can trigger action potentials (excitable cells)
- highly polarised (two ends of the neurones are very different to each other)
What are the physiological differences between axons and dendrites?
- axons: propagate information
- Dendrites: receive information
What are the differences between the organelles in axons and dendrites?
- axons: synaptic vesicles
- Dendrites: rough ER, ribosomes, golgi
What are the structural differences between Axons and Dendrites?
- axons: long (mm-m), untapered, branch at 90 degrees
- dendrites: short, tapered (reduce in thickness), branched
What are the specialisations in axons and dendrites?
- axon: terminal
- Dendrite: dendritic spines
Are axons or dendrites often myelinated?
Axons
What are the cytosolic organelles in a neuron?
- Perodisomes, mitochondria
- Ribosomes
- Vacuolar apparatus (secretory pathway/ endocytic pathway)
Endoplasmic reticulum
Secretory vesicles
Golgi complex
Endosomes
Lysosomes
What are the divisions at the axon hillock?
- Synaptic vesicles
- Mitochondria
- Smooth ER
What are the features of the membrane in dendrites?
Ca2+ channels
Ligand-gated ion channels (glutamate receptors)
G-protein coupled receptors
What are the features of the membrane in Axons?
G-protein coupled receptors (terminals)
Ca2+ channels (terminals)
Na+ and K+ channels (axon shafts)
What does the neuronal cytoskeleton help with?
with getting the proteins to the right place as there are no ribosomes in axons
What is the role of the neuronal cytoskeleton?
- Structural support – shape and calibre of axons and dendrites
- Transports cargo to and from axons and dendrites
- Tethering of components at membrane surface
What is the Neuronal cytoskeleton made up of?
- microtubules
- neurofilaments
- microfilaments
What are the features of microtubules?
Role: structure and transport
Run longitudinally down axons and dendrites
Big, 20nm wide, tubulin polymers
Polymerisation/ Depolymerisation – so can help with shape change
Microtubule associated proteins e.g. MAP-2, Tau Kinesin and Dynein
What are the features of Neurofilaments?
Role: mechanical strength
10nm wide filamentous protein threads
What are the features of microfilaments?
Role: mediate shape change
5nm wide, actin polymers
Tethered to membrane
What are Bipolar, Unipolar and Multipolar neurons?
- Bipolar
Two cell processes coming from the cell body - Unipolar
One process coming from the cell body - Multipolar
Lots of processes coming from the cell body
What are sensory neurons?
(afferent; somatic (originates from body) or visceral) neurons originate from sensory receptors to the ‘processor’
What are motor neurons?
(efferent; somatic or visceral) neurons conduct signals that originated in the CNS
What are Interneurons?
Between sensory and motor neurons
Do dendrites have a high or low concentration of sodium channels, and where are they mostly found?
Have a low density of sodium channels, mostly found in grey matter.
What is the Axon hillock/ action potential zone?
where the cell body starts an action potential. High concentration of sodium channels. Marks the boundary between the cell body and axon
What is a myelin sheath?
myelin is an insulating material produced by Schwann cells and oligodendrocytes
What are the Nodes of Ranvier?
gaps in the myelin sheath where there is a high concentration of sodium channels. The nodes allow an action potential to regenerate as it passes down the axon
Where are axons usually found?
in the spinal cord as grey and white matter
What are nerve terminals?
specialised regions of a neuron that form part of the synapse. Contain synaptic vesicles – packets of neurotransmitter that are released into the synapse when signals are passed from a neuron to another cell
What promotes the regrowth of actions in the peripheral nervous system and why doesn’t this work in the CNS?
- Schwann cells
- We lack Schwann cells in the central nervous system
What happens after there is damage in the CNS with astrocytes?
if there is damage in the CNS the space that was caused by the damage is often quickly filled by astrocyte scar tissue because they reproduce so quickly
What is the Neurilemma?
the plasma membrane of the Shwann cell that is wrapped around the axon of a peripheral neuron.
Why can repair to neurons only take place in axons?
Because it needs a myelin sheath
What must remain intact for repair to a neuron to take place?
The Neurosoma
What happens in the repair of damaged neurons?
- Nissl bodies inside the cell body breaks down and spreads out throughout the cell body
- Nissl bodies are granules of RER (rER has lots of ribosomes in it – leading to lots of protein synthesis)
- Part of axon distal to injury site degenerates and breaks down (wallerian degeneration)
- The segment of the axon proximal to the injury site starts to break down but only to the next node of Ranvier and only inside the neurilemma (retrograde degeneration)
- The neurilemma forms a regeneration tube which guides the axon through regrowth from the most proximal node of Ranvier to where the terminal was
When may regeneration not occur in the peripheral nervous system?
If the Shwann cells are too damaged themselves
What can neurons and glia cells both release and respond to?
Signalling molecules
What is usually the longest length a dendrite can be?
2mm
How is the inside of a neuron separated from the outside?
By a neuronal membrane
What is the difference between ribosomes depending on whether they are destined or not to reside within the cytosol of the neuron?
If the ribosome is destined to reside within the cytosol of the neuron then the ribosomes generally exist as free ribosomes, if it is destined to be inserted into the membrane of the cell or an organelle then it is synthesised on the rough ER
What is the diameter of the cell body/ soma?
about 20um
What is the movement of material down the axon called?
axoplasmic transport
When does Wallerian degeneration happen and why?
when axons are cut and separated from the cell body. It occurs because the normal flow of materials from the soma to the axon terminal is interrupted
Where does Kinesin move material?
From the soma to the terminal
What is anterograde transport?
Movement of material from the soma to the terminal
What are stellate cells and pyramidal cells?
- Stellate cells are star shaped dendrite s
* Pyramidal cells are pyramid shaped dendrites
How are neurons whose dendrites have spines and those that don’t classified?
Neurones whose dendrites have spines are called spiny and those that don’t are called aspinous
