Week 3 - Cells of the brain Flashcards
In which century did studying individual brain cells start to become possible?
19th Century
Who was one of the pioneers of the study of individual brain cells?
Camilio Golgi (1843 - 1926)
Who first showed that the brain consists of billions of interconnected neurons?
Santiago Ramon y Cajal (1852 - 1934)
What is a neurofibrillary tangle?
Aggregates of a specific protein which is a primary biomarker of Alzheimer’s disease
What are amyloid plaques?
Extracellular deposits of the amyloid beta protein - large numbers of which are characteristic of Alzheimer’s disease
What does the new immunohistochemical technique called CLARITY enable?
Allows visualisation of brain cells in situ
What structural feature has CLARITY uncovered in the tissue sample of a 7-yo boy with autism?
‘Ladder-like’ structures in the frontal lobe, where single neurons formed connections back onto themselves and to other neurons
Roughly how many neurons are there in the brain?
86 billion
What is the ratio of glial cells to neurons thought to be?
Previously thought to be 50 : 1 but now thought to potentially be closer to 1 : 1
Is the ratio of glial cells to neurons consistent across the brain?
No - it differs between brain regions
What can cause neurons to differ in shape and size?
- Their location in the nervous system
- Their function
What are some traits of a motor neuron?
- Roughly spherical cell body
- Branches of dendrites merge to form several larger dendrites directly attached to the cell body
- Their axons carry information to the spinal cord and out to effector organs such as muscles
What are some traits of a granule cell?
- Found in cerebellum and other brain regions
- Very small cell body
- One of the most numerous cell types in the brain
- Small number of dendrites
- Axon travels a short distance then divides in two
- Varied functions depending on location
What are some traits of Purkinje cells?
- Found in the outer layer of the cerebellum
- Send information to cells deeper within the cerebellum
- Among the largest cells in the brain
- Highly branched and numerous dendrites
What are some traits of pyramidal cells?
- They are large
- Found mainly in the cerebral cortex
- Also found in hippocampus and amygdala
- Carry information long distances within and outside of the brain
What is the function of dendrites?
To receive information and pass it to the cell body for processing
What is the purpose of the axon?
It passes on information from the cell body to the axon terminals in the form of an action potential
What are dendritic spines?
Small protrusions from dendrites that form the postsynaptic component of synaptic connections from other neurons
What are the main types of glial cells?
- Astrocyte
- Ependymal cell
- Oligodendrocyte
- Microglial cell
What are some features of astrocytes?
- Form part of the blood-brain barrier
- Regulate concentration of ions and neurotransmitters around neurons
- Help regulate oxygen and nutrient supplies to neurons
- Protective and structural role
- Help regulate immune and inflammatory responses
What are some features of ependymal cells?
- Filter plasma from the blood to produce CSF
- Aid in circulation of CSF around the CNS
What are some features of oligodendrocytes?
- Form myelin around axons of neurons in order to increase the speed of transmission of electrical information
What are some features of microglial cells?
- Remove bacteria and debris from dead and dying cells
- Involved in immunological response to pathogens
- Provide growth factors for formation of blood vessels and glial cells
Why are astrocytes so important in the brain?
- Form part of the neurovascular unit
- Send projections to neurons and around blood vessels
- Can detect increase in neuronal activity and signal blood vessels to dilate in order to increase bloody supply to active brain regions
What types of roles do astrocytes have?
- Part of the neurovascular unit
- Influence synaptic transmission
- Mediate immune response and inflammatory response in the brain
- Involved in generation of new synapses
What condition has been linked to a reduction in astrocyte numbers in certain brain regions?
Depression
Roughly how many connections can one neuron have with others?
Up to 15000
What three things is a synapse a combination of?
- Presynaptic endings
- Synaptic cleft
- Postsynaptic endings
What are synapses?
The connections between neurons
What is synaptic transmission?
The flow of information across a synapse from the presynaptic neuron to the postsynaptic neuron
What is an action potential?
The basic events which nerve cells use to transmit information from one place to another
What causes an action potential?
Depolarisation of the neuron membrane
When does an action potential occur?
When information is sent away from the neuron’s cell body
When an action potential reaches the axon terminal what determines what then happens?
If the synapse is either electrical or chemical
What happens when an action potential reaches an electrical synapse?
The electrical signal passes from one neuron to the next via gap junctions
What happens when an action potential reaches a chemical synapse?
It triggers the release of neurotransmitters which influence the postsynaptic neurons
Are electrical or chemical synpases more common within the CNS?
Chemical
What are the characteristics of an axon terminal?
- The enlarged zone at the end of an axon that forms the synapse with the postsynaptic neuron
- It releases neurotransmitters
What are the key neurotransmitters?
- GABA and glutamate (GABA is inhibitory, glutamate almost always excitatory)
- Catecholamines (e.g. dopamine, noradrenalin - important in mental health)
- Serotonin (also important in mental health)
What is a synaptic cleft?
- The small gap between the presynaptic and postsynaptic neuron
- Where the neurotransmitter is released into by the presynaptic neuron
What are synaptic vesicles?
Small packages in the presynaptic axon terminal that contain many molecules of neurotransmitter ready to be released into the synapse
What is an axon terminal?
The region at the end of the axon where the neurotransmitter is released
What is a dendrite?
The area of the postsynaptic neuron that receives the signal from the presynaptic neuron
What are synaptic vesicles?
Packages containing neurotransmitter molecules ready for release at the synapse
What is a neurotransmitter?
A signalling molecule that communicates information between neurons via the synapse
What are postsynaptic receptors?
Proteins located on the dendrites of the postsynaptic neuron that bind neurotransmitters
What is the difference between a hormone and a neurotransmitter?
- Hormones are generally released into the bloodstream and travel the body
- Neurotransmitters are released from neurons and act on neighbouring neurons or other cells in close proximity
Where are neurotransmitters synthesised?
Either in the axon terminal or the cell bodies or neurons
What is a neuromodulator?
Something that potentiates or inhibits the transmission of a nerve impulse but is not the actual means of transmission
What are the key stages of synaptic transmission?
- Synthesis and storage
- Neurotransmitter release
- Neurotransmitter postsynaptic receptors
- Inactivation of neurotransmitters
Where does chemical neurotransmission take place?
At the synapse between the axon terminal of a presynaptic neuron and the dendrites of a postsynaptic neuron
What does an excitatory postsynaptic potential (EPSP) do?
Brings the postsynaptic neuron closer to the threshold for firing an action potential
What does an inhibitory postsynaptic potential (IPSP) do?
Takes the postsynaptic neuron further from the threshold for firing an action potential
If a neuron receives an excitatory stimulus, what will happen to its rate of firing action potentials?
It will increase in accordance with the level of the stimulus
What is the order of events that take place at the synapse?
- Action potential reaches axon terminal
- Synaptic vesicles fuse wtih membrane of axon terminal
- Neurotransmitter released into synaptic cleft
- Neurotransmitter diffuses across cleft
- Neurotransmitter binds to receptors on postsynaptic neuron
- Binding creates change in excitability of postsynaptic neuron
- If great enough excitation, action potential is initiated in postsynaptic neuron
Do specific neurotransmitters always have the same effect?
No - some can be either inhibitory OR excitatory
What is synaptic integration?
A process which describes how neurons integrate the received signals from postsynaptic neurons before the generation of a nerve impulse
What are autoreceptors?
Receptors found on the axon terminal of presynaptic neurons that can regulate the release of neurotransmitter
What is an axon?
Part of the neuron that extends from the cell body out to the axon terminal where synapses with adjacent neurons are formed
What type of feedback loop does binding of neurotransmitter to autoreceptor create?
Negative
Where are autoreceptors located?
On axon terminals
What is synaptic reuptake?
A process which helps terminate the action of a neurotransmitter by removing it from the synaptic cleft
Where in the brain does synaptic reuptake occur?
Specialist reuptake channels in the axon terminal
What are the ways neurotransmitter can be removed from synapses?
- Synaptic reuptake
- Enzymatic degradation
- Diffusing away from the synapse and being taken up into astrocytes
What problem may occur if levels of neurotransmitter are too high?
Neuronal toxicity
What will happen if a drug that blocks reuptake of a neurotransmitter is introduced to the synapse?
The neurotransmitter will remain in the synaptic cleft for longer and thus its effect on the postsynaptic neuron will be prolonged
What is a synapse?
The junction between the axon terminal of a presynaptic neuron and the dendrite of a postsynaptic neuron
What function does a synapse perform?
It is where information is passed from the presynaptic to the postsynaptic neuron
What initiates synaptic transmission?
The arrival of an action potential at the axon terminal of a neuron
Synaptic transmisison triggers what process?
The release of neurotransmitter into the synaptic cleft
What does neurotransmitter do?
Diffuses across the synaptic cleft and binds to receptors on the dendrite of the postsynaptic neuron
Which part of the postsynaptic neuron does neurotransmitter bind to?
The dendrite
Is GABA classed as an inhibitory or excitatory neurotransmitter?
Inhibitory
Is glutamate classed as an inhibitory or excitatory neurotransmitter?
Excitatory
As well as the dendrite of the postsynaptic neuron, what else can neurotransmitter also bind to?
Autoreceptors on the presynaptic axon terminal
What happens if neurotransmitter binds to autoreceptors on the presynaptic axon terminal?
It can affect the amount of neurotransmitter that is released
What are cholinergic neurons?
Neurons which utilise acetylcholine as the principle neurotransmitter
Where do the two cholinergic pathways originate?
- The pons
- Basal forebrain
Where do the cholinergic neuronal pathways which originate in the pons project to?
- Down towards the spinal cord
- Up through the brain
- Hippocampus
A reduction in hippocampal functioning is associated with which condition?
Alzheimer’s
If there is reduced activity in the cholinergic pathway which starts in the pons and ends in the hippocampus, what effect is observed?
Loss of spatial memory, associated with Alzheimer’s
Where do the cholinergic pathways which originate in the basal forebrain project to?
- The hippocampus
- The cortex
- Other brain regions such as prefrontal cortex
What are the four neurotransmitter pathways?
- Acetylcholine pathway
- Dopamine pathway
- Noradrenaline pathway
- Serotonin pathway
How many principle dopamine pathways are in the brain?
Three
What are the names of the three dopamine pathways?
- Nigrostriatal pathway
- Mesolimbic pathway
- Mesocortical pathway
Where does the nigrostriatal pathway run from and to?
From the substantia nigra in the midbrain to the caudate nucleus and putamen in the striatum
What is the nigrostriatal pathway important for?
The production of movement
Loss of the nigrostriatal pathway underlies which disease?
Parkinson’s disease
Where does the mesolimbic pathway extend from and to?
The vental tegmental area of the midbrain to the nucleus accumbens in the ventral striatium
Where does the mesocortical pathway extend from and to?
From the ventral tegmental area of the midbrain to the prefrontal cortex
What are the mesolimbic and mesocortical pathways together known as?
The reward pathways
What behaviours are the mesolimbic and mesocortical pathways involved with?
Addictive behaviour - activity in these pathways results in ‘feelgood’ sensations
Where do noradrenergic pathways originate?
The locus coeruleus, in the brain stem
Where do noradrenergic pathways project to?
- Hypothalamus
- Amygdala
- Thalamus
- Through the cortex
What are noradrenergic pathways involved with?
Control of the responses of the CNS - e.g. altering heart rate in response to a threat
Why is the projection of the noradrenergic pathway to the prefrontal cortex thought to be important?
It is believed to be the target of some drugs which treat depression
Where do serotonergic pathways in the brain originate?
The raphe nuclei in the brain stem
What areas do serotonergic pathways project to?
- Cerebellum
- Hippocampus
- Prefrontal cortex
What are some of the functions that serotonergic pathways have roles in?
- Sleep/wake cycle
- Emotions
- Mood
Disruptions in serotonergic pathways are of importance with regards to which condition?
Depression
What are cholinergic pathways important for?
Understanding dementia
In what ways might drugs which interfere with synaptic transmission?
- Binding with postsynaptic receptors and autoreceptors thus interfering with the action of neurotransmitters
- Processes which terminate the activity of a neurotransmitter
What is an antagonist?
A drug which binds to a receptor and has no effect on a neuron but which prevents binding of the neurotransmitter
What is an agonist?
Molecules that bind to a receptor and have a similar effect on the neuron to the neurotransmitter that usually binds to that receptor
In which set of circumstances would an agonist be useful?
If there is a deficiency in a particular neurotransmitter pathway
If a dopamine agonist is present, what happens to the action potenial firing rate in the neuron?
It increases
What is an excellent example of neuroplasticity?
The changes which occur in the brains of London taxi drivers who have undertaken “The Knowledge”
What part of the brain is notably different in London taxi drivers?
The hippocampus
What are the main reasons that changes take place in the brain?
- Development / ageing
- Learning & experiences
- Disease processes
- Recovery from brain injury
What is synaptogenisis?
The growth of new synapses between neurons
What is dendritic pruning?
A process which underpins neuroplasticity
What occurs as a result of dendritic pruning?
Dendritic spines are removed from dendrites, which reshapes the connectivity between neurons
When does dendritic pruning peak?
During adolescence and into early adulthood
What can occur if there is prolonged or intense activity in one neuron?
The next neuron in the pathway may become increasingly responsive
What is the paraphrased definition of “Hebbian plasticity”?
“Neurons that fire together, wire together”
Roughly how many branches do dendrites have at a time?
Four to five
What is electrophysiology?
A technique used to record from individual brain cells in animals
Which brain imaging technique allows activity across the brain to be measured?
Electroencephalography (EEG)
What are the different types of brain waves?
- Gamma waves (role unclear)
- Beta waves (active concentration)
- Alpha waves (drowsy/meditative state)
- Theta waves (as above)
- Delta waves (deep sleep)
What are the main changes in the brain associated with Alzheimer’s?
- Enlarged ventricles
- Reduced grey matter
- Appearance of protein deposits
Deficits in memory are linked to which part of the brain?
- Medial temporal lobe
What are some of the conditions which are linked to the default mode network?
- ADHD
- Autism
- Depression
Dopamine agonists can be helpful in treating which condition?
Psychosis
