Composition of the Nervous System Flashcards
Karen Cullen + Richard Ward
How many neurons does the human brain have?
• Made of 100 billion neurons
What is the human brain made of?
- Made of lipids, proteins, white matter (which makes up most of the brain) and grey matter
- Oligodendrocyte membranes make up most of the lipids in the brain
- Most of the brain’s volume is not neurons- the brain is mostly glial cells
How much oxygen does the brain use?
• Uses 20% of body’s oxygen, which is mostly used by grey matter
How much blood supply does the brain use at rest?
• Uses 15-25% of total blood supply at rest
What is the nervous system?
• Nervous system- An organised association of neurons and supporting cells (glia) with its own blood supply (endothelial cells)
What are neurons?
• Neurons- Excitable cell responsible for transfer of information of information via electrical (ionic movement) and chemical communication unidirectionally via specialised junctions (synapses) to other excitable cells
What are endothelial cells?
o Line blood vessels and form the blood brain barrier
Describe how an action is made by the nervous system based on sensory input
o Sensory input (Peripheral nervous system) Integration (Central nervous system) Motor output (peripheral nervous system
Sensory system (afferent-towards)
• Unidirectional signal of neurons from the periphery towards the central nervous system
o The trigger of the signal may be from outside the body or internal which is transduced by a special sense organ/structure and transmitted for interpretation/integration
Motor system (efferent-away)
• Direction of signal is toward the periphery, away from the nervous system and consists of voluntary and involuntary signals
What is the direction of a signal in a neuron?
• Direction of signal passage is constant and unidirectional and goes from the dendrite to the cell body to the axon
o However, many sensory systems don’t have dendrites on their neurons, but a receptive end which is where the signal passage starts
• Neuron signalling-
o Dendrites collect electrical signals
o Soma contains nucleus and organelles that keeps the cells alive
o Axon passes the signal onto dendrites of another neuron or to an effector such as a muscle cell
What is a neuron made of (its microanatomy)?
-Cell body/soma/perikaryon
-Neuronal cytoskeleton
-Dendrites
-Axon hillock
-Axon
-Terminal Bouton
-Synapse
-Neuronal
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Describe what is in the soma of a neuron and the function of these organelles
Contains cytosol- salty, potassium rich solution inside the cell
Contains a 5-10 um nucleus, containing DNA, which is surrounded by the nuclear envelope
Contains a nucleolus, an organelle actively engaged in ribosome synthesis, rich in RNA
Abundant free ribosomes and prominent rough endoplasmic reticulum
A prominent Golgi apparatus for processing and packaging proteins into vesicles that are destined for delivery to different parts of the neuron
Abundant mitochondria which is site of oxidative metabolism
How big is a neuron’s soma?
Typical neuron has 15-20um diameter soma but can be as large as 50um
Describe Nissi bodies in neurons (why they are important, how they can be used for identification, their size)
• The rough endoplasmic reticulum is called Nissi bodies
o Most abundant organelle in the neuronal soma which can be visibly seen in a cell stain and is made up of membrane stacks dotted with ribosomes (which are rich in RNA)
Can tell difference between neuron cell bodies and other cells as nissi bodies are visible in neuron cell bodies
o About 25 nm diameter
o Sites of protein synthesis
o Neurons have massive protein production and very high metabolic activity
o Makes proteins in neurons such as neurotransmitter enzymes, channels, pumps, cytoskeleton…
o Neurotransmitter enzyme, channel and pump synthesis takes up the most energy in the body
Describe ribosomes in neurons (location and function)
o Make proteins
o Are attached to the rough ER or free in the cell
If the protein is destined to reside within the cytosol of the neuron, what ribosome is it made with?
o If the protein is destined to reside within the cytosol of the neuron, then it is made by free ribosomes
If the protein is destined to be inserted into the membrane of the cell or an organelle, what ribosome is it made with?
o If the protein is destined to be inserted into the membrane of the cell or an organelle, it is synthesised on the rough ER
Describe the function of the neuronal cytoskeleton
Provides structural support
Supports movement of proteins and organelles along axons
Contractile properties such as in growth cone extension and dendritic spine formation
What 3 protein types is the neuronal cytoskeleton made of, and what are each of their sizes, location and composition?
Made of 3 protein types
• Neurofilament
o Intermediate filament class
o Measures 10nm
• Microtubules
o Run longitudinally down neurites (axons and dendrites)
o Composed of protein tubulin
o Measures 20nm in diameter
• Microfilaments
o Measure only 5nm in diameter
o Numerous in axons and dendrites
o Made of protein actin
Describe what dendrites are and how long they are
o Dendrites-a lot of shorter fibres extending from the cell body
Rarely longer than 2mm
Have polyribosomes
Dendrites of some neurons are covered with dendritic spines that receive some types of synaptic input
Dendrites are covered with synapses
What is a dendritic branch?
A single dendrite is called a dendritic branch
What is a dendritic tree?
Dendritic tree- the dendrites of a single neuron
What is an axon hillock?
junction between soma and axon where the axon potential fires or does not fire
What is the role and composition of an axon hillock?
Plays essential role in integration and transmission of signals
High density of sodium channels- decision spot on whether axon fires or not
• Region of summation of excitatory and inhibitory neural input: the action potential is usually generated at the axon hillock
Has transmembrane protein barriers made of actin filaments that block free diffusion of proteins from soma to axon and segregates key components such as channels and pumps
What is an axon and what are its dimensions?
Axon length can be mms to meters long
Cytoplasmic extension of the neuron
Very thin (about 1-25 um in diameter in most humans)
May be very long (can be more than 1 meter in humans)
What is the role of an axon?
Carries information from the soma to another neuron or effector cell
Can axons make their own proteins?
Has no ribosomes, so proteins of the axon must be synthesised in the soma and then shipped down the axon
What is a terminal bouton?
The site where the axon comes into contact with the neurons and passes information on to them
Contains synaptic vesicles
Has numerous mitochondria but no microtubules
What is a synapse and what are its components?
Specialised junctions between neurons where information passes from one neuron to another through chemical messages such as neurotransmitters or electrical impulses (communicating by gap junction)
Made of presynaptic neuron, Postsynaptic neuron, Synaptic cleft and Terminal bouton
Where can synapses be found?
Synapses are most often between
• Axon terminal boutons and dendrites: axodendritic
• Axon terminals and perikaryal (neuronal cell bodies)
• Axons: axo-axonic (such as in presynaptic inhibition)
What is the composition of the neuronal membrane?
Composition- phospholipid bilayer and special embedded proteins include ion channels and carrier proteins. Is about 5nm thick.
• Phospholipid bilayer: hydrophilic phosphate heads in extracellular part and hydrophobic lipid tail embedded in the membrane
What is the function of the neuronal membrane?
Function- preserves the highly-controlled internal environment necessary for an action potential and for transmission of the signal from the presynaptic to the postsynaptic neuron or muscle cell
Describe the relative concentrations of key ions across the neuronal membrane
o Potassium- 1 outside:20 inside Higher concentration on inside of cell o Sodium- 10 outside:1 inside Higher concentration outside of cell o Calcium- 10000 outside:1 inside Higher concentration outside of cell o Chlorine- 11.5 outside:1 inside Higher concentration outside of cell
How does the neuronal membrane support ion segregation?
- Passive phospholipid membrane properties
- Passive (don’t need ATP to operate) ion channels
- Active (need ATP to operate) carrier proteins (pumps)
How do passive phospholipid membrane properties support the neuronal membrane’s ion segregation?
(includes what can and can’t diffuse through the lipid bilayer, why they can/can’t and what are the consequences of this)
o Diffusion of ions through the membrane is restricted as some ions don’t move through the lipid bilayer as they are not soluble in the lipid bilayer
Lipid soluble items that freely diffuse through the cell membrane include oxygen, nitrogen, carbon dioxide and alcohols
Water diffuses through the lipid bilayer as it is small and has high kinetic energy (even if it is not lipid soluble)
Ions do not diffuse through the membrane for 2 reasons
• Ions become hydrated in the watery environment and become too large
• Polarities of the phosphate head repel the ion charge
The fact that ions cannot diffuse through the neuronal membrane means that once ions are in or out, they cannot naturally diffuse through and go in or out on their own, but need a channel or pump to transfer
Are most ion channels ion specific?
Yes
What does movement of any ion through its channel depend on?
o Movement of any ion through its channel depends on the concentration gradient and the difference in electrical potential across the membrane
What two types of channels are there?
Gated
Non-gated
What are non-gated ion channels?
o Non-gated ion channels- always open and the ions can always go through
What are gated ion channels?
o Gated ion channels-open or closed depending on stimulus
What are 3 types of gated ion channels and what do they respond to?
Voltage-gated ion channels are open or closed depending on the charge
Ligand-gated ion channels are open or closed depending on the neurotransmitter
Transduction gated are open or closed depending on mechanical forces
Describe when the voltage-gated sodium channel is open or closed and how quickly they do so
o Closed at resting potential (-65mV) o Begins opening between -65mV and -40mV o Sodium flows into the cell o Fully opens at -15mV o Closes at +35mV o Open with little delay o Stay open for about 1 msec then close o Cannot be opened again by depolarization until the membrane potential returns to a negative value near threshold
What determines sensitivity of depolarisation of neurons?
o Density of voltage-gated sodium channels determines sensitivity to depolarisation
Where is there the highest density of sodium voltage-gated channels on a neuron?
o Highest density at axon hillock: allows generation of action potential down the axon
Describe when the voltage-gated potassium channel is open or closed
o Closed at resting potential (-65mV) o Begins to open at +30 to 35mV o Potassium flows out of cell o Closes at resting potential (-65mV) o Do not open immediately: takes about 1msec for them to open
What is active transport?
o Active transport- pumps transport ions across the membrane against the gradient from low to high concentration
What maintains neuronal resting potential and how?
o Pumps maintain the neuronal resting potential (-65mV)
Sodium-Potassium exchanges internal sodium for external potassium
Calcium pumps- actively transports calcium ions out of the cytosol across the cell membrane
o Pumps re-establish the potential after firing
What is the resting potential of a neuron?
-65mV
Describe how information is encoded in neurons
• Information is encoded in the frequency of action potentials of individual neurons as well as the distribution and number of neurons firing action potentials in a give nerve
What is essential for neuronal transmission and what does it result in?
- Ion segregation is essential for neuronal transmission
* Ion segregation results in a charge potential across the neuronal membrane
What is a charge potential?
o Charge potential: difference in concentration of negative and positive ions
When a neuron is polarised, is the inside of the cell more positive than the outside or vice-versa?
• When a neuron is polarised (at rest), the inside of the cell is more negative than the outside
What is an action potential?
• Action potential- when the membrane becomes more positively charged relative to the outside. Lasts about 2 milliseconds
• The action potential is unidirectional and of fixed size and fixed duration
o Sodium channels close behind action potential
o Potassium channels open behind action potential
o Trailing end of axon where refractory period occurs immediately (gets a while to take back to resting potential to where cell can be excited again)
What are the stages of an action potential? Describe each of them
- Resting potential
The voltage across the membrane is about -65 mV at resting potential - Gets triggered
Near the terminal bouton, there are voltage-gated calcium channels
When an action potential fires and gets down to terminal, action potential opens calcium channels which will call the synaptic vesicles to dock and release their neurotransmitters
Neurotransmitter binds to ligand-binding neurotransmitter receptor which opens up sodium channels which starts making the cell depolarised
When the threshold is surpassed (-55mV), an action potential occurs
• An action potential is ONLY caused when the depolarization of the membrane is beyond the threshold
• Threshold-the membrane potential at which enough voltage-gated sodium channels open so that the relative ionic permeability of the membrane favors sodium over potassium. - Rising phase
Sodium channels open and inside of cell becomes more positive as sodium enters in the cell - Overshoot
Voltage is about +35 mV- the part where the inside of the neuron is positively charged with respect to the outside - Falling phase
Potassium channels open and inside of cell becomes less positive, returns to negative
Sodium channels close - Undershoot
Rapid depolarisation causes the inside of the membrane to be more negative than the resting potential - Absolute refractory period
Sodium channels inactive when the membrane becomes strongly depolarised. They cannot be activated again, and another action potential cannot be generated, until the membrane potential becomes sufficiently negative enough to deinactivate the channels (usually 1msec) - Relative refractory period
The membrane potential stays hyperpolarised until the voltage-gated potassium channels close. Therefore, more depolarizing current is required to bring the membrane potential to threshold - Restoration of the resting potential
Describe how unidirectional signal is supported by the microanatomy of the neuron
o Unidirectional signal is supported by the microanatomy of the neuron
Different regions of the neuronal cell have different densities of voltage and ligand gated channels
• High density of ligand-gated ion channels at the dendrites
• High density of voltage-gated ion channels at the axon hillock and along the axon
How many glial cells are there in relation to neurons, and as the brain evolves
Brain mostly made up of glial cells- there are 10x as many glial cells as neurons (approximately)
• Glial to neuron ratio increases as brain evolves
How many synapses might each astrocyte enclose?
• Each astrocyte may enclose more than 2 million synapses
How many axons do oligodendrocytes wrap?
• Oligodendrocytes wrap billions of axons
What are the 2 major glial cell categories?
- Macroglia (astrocytes and oligodendrocytes)
- Microglia
What are two types of macroglia and where do they reside?
-Astrocytes
-Oligodendrocytes
o Central Nervous Systems
What cell type do astrocytes and oligodendrocytes come from?
Come from neural stem cells (like neurons)
How are astrocytes produced?
o Neural stem cell-> Glial Progenitor -> Astrocyte precursor-> Astrocyte OR Neural Stem Cell -> Glial Progenitor -> O-2A cells-> Astrocytes
What are two different types of astrocytes?
o Fibrillary astrocytes in white matter-contact nodes of Ranvier
o Protoplasmic astrocytes in grey matter- closely associated with synapses
How are astrocytes visualised
• Visualisation
o Labelled with immunohistochemistry using antibodies against glial fibrillary acidic protein (GFAP)
What is GFAP?
GFAP is an intermediate filament protein
GFAP is a component of the cytoskeleton
The cytoskeleton confers strength and shape to cells
GFAP is specific to astrocytes
Describe how much space glial cells take up in the brain and why
o Glial cells have a large volume and fill up space in the brain to maintain fluid balance and structural integrity- there is very little space in the brain
What happened to the astrocyte: neuron ratio as the brain evolved?
o As evolution occurred, the increase in number and complexity of astrocytes in more evolved brains is much greater than the increase in neuronal number
What are the functions of astrocytes?
o Provide structural support for the central nervous system
o Invest endothelium and induce blood brain barrier tight junctions
o Provide support for synapse formation and maintenance
o Guide neuronal process growth and regulate neurogenesis
o Maintain biochemical balance around neurons
o Forms scar tissue
o Supports neuroinflammatory system
o Form gap junctions with neighbouring astrocytes and communicate with them
How do astrocytes provide structural support for the central nervous system
Astrocytic processes are joined by cell-cell contacts: confers structural strength
Astrocytes stabilise neuronal configurations (wrap terminals)
Astrocytic processes interweave between neuronal processes
Form glia limitans: dense, fibrous GFAP network around brain that gives it structural integrity
• Astrocytic processes invest outer surfaces of CNS and envelop blood vessels, forming the glia limitans
How do astrocytes invest endothelium and induce blood brain barrier tight junctions?
Astrocytic endfeet wrap capillary: are on more than 90% of endothelial cell surface and induce endothelial cells to form the blood brain barrier
The blood brain barrier is tight junctions between endothelial cells
In the absence of astrocytes, endothelial cells do not form tight junctions
What is a neurovascular unit?
Neurovascular unit-contains endothelial cells, neurons and glial cells
How do astrocytes provide support for synapse formation and maintenance?
Astrocytes isolate neurons and ensure that receptive neuronal surfaces are protected from non-specific influences
Astrocytes support synaptic microanatomy and envelope neuronal terminals
• Astrocyte processes are especially dense in areas of intense synaptic activity
Synaptic remodelling
How do astrocytes remodel synapses?
• Removes degenerating synapses
• Astrocytes can swell or relax depending on water concentration in region due to their aquaporin channels which let water in the cell
o Astrocytic swelling can change synaptic distance, hence changing neuronal firing efficiency
The smaller the synaptic cleft, the more efficient the synapse
How do astrocytes guide neuronal process growth and blood vessel growth and regulate neurogenesis
Astrocytes promote angiogenesis, the growth of new blood vessels
Synapse number and efficacy are significantly compromised in a glia-less environment
Radial astroglial processes provide tracks along which neurons migrate during development
• Provide a temporary scaffold for the migration of newborn cortical and cerebellar neurons
o Long radial fibers extend from the ventricular to the pial surface and serve as guidance cables
Major sources of extracellular matrix proteins, adhesion molecules and neurotrophic factors
Describe how astrocytes maintain biochemical balance around neurons
Glutamate-glutamine cycle
Redistribute potassium during neural transmission
• Has a Sodium-Potassium-ATPase pump (which gets ATP from glucose lactate conversion) which brings potassium in the astrocyte and drives sodium out the astrocyte, helping keep resting potential and keeping ionic balance in order
Remove glutamate and GABA at the synapse
Synthesise glutamate and GABA precursors
Detoxify ammonia
Provide energy substrates (lactate) to neurons
• Astrocytes source of energy that neurons use
• Astrocytes take glucose from the capillary and convert it into lactate, which is given to the neuron as an energy source
Maintains brain/water homeostasis
Envelop synaptic junctions in the brain and restrict the spread of neurotransmitter molecules that have been released
Tripartite synapse model- glia actively communicates with pre and post-synaptic neurons
• Neurotransmitters released by presynaptic neurons do not only signal to post-synaptic neurons and terminal astrocytes, but can also trigger massive calcium waves through astrocytic networks, which could transmit synaptic signals over extensive cortical areas
Describe the astrocyte glutamate-glutamine cycle
Glutamate-glutamine cycle
• Astrocytes remove toxic glutamate from the synaptic cleft and combines it with ammonia
o Glutamate is an excitatory neurotransmitter, and excess glutamate can be neurotoxic
• Through glutamine synthetase in the astrocyte, it is transformed into glutamine, which is not toxic to the neuron, and provides glutamine to the neuron
o Glutamine synthetase requires ATP, which is given by converting glucose into lactate
• In the neuron, glutamine is transformed into glutamate through glutaminase
How do astrocytes form scar tissue?
o Forms scar tissue
Astrocytic scars made of GFAP form around where neurons are injured or dying
• Cells fill with GFAP and extracellular matrix proteins and makes scar stronger and walls off injured area
o GFAP stays within the cell, which becomes enlarged and more rigid
Astrocytic scars can interfere with re-growth of neuronal processes in CNS (partly accounts for poor CNS regeneration)