Neuroscience Flashcards
(108 cards)
1
Q
Describe a hypothetical multicellular organism to model the nervous system
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2
Q
What are the timescales for diffusion in cells
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As distance (size of organism) increases = takes longer for molecule to diffuse
So diffusion of molecules across an axon could take days
3
Q
How is moving material across an axon studied
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4
Q
What are the two major cytoskeleton elements in neurons
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5
Q
What are the different components of neurons
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6
Q
What is meant by:
Axon initial segment
Anterograde
Retrograde
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7
Q
What is the basics for how the nervous system works
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8
Q
How much energy is needed move a charged molecule through a membrane
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9
Q
Why membrane channels are needed
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10
Q
What are ion pumps needed for
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11
Q
How does the sodium-potassium ATPase work*
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[Na+] outside cell > inside cell
[K+] inside cell > outside cell
Inside cell -70mV (more negative that outside cell
These conc differences regulated by active trabsport
12
Q
What are the concentrations of Na+, Cl-, K+ and Ca2+ inside and outside a cell
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13
Q
Explain equilibrium potentials with the example of K+
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All systems move towards equilibrium – where the tendency for further change vanishes
• Consider a bath separated by a membrane permeable
only to K+ ions. A high concentration of a salt (KA) is
introduced into one side (the left hand side) and a low
concentration on the other side.
• We also have a voltmeter to measure membrane
potential
In the first instance (on the left) the voltmeter reads 0 mV as both sides are neutral.
• However, K ions start to diffuse down their concentration gradient from one side to the other – left to right.
• This gives an excess of positive charge on the right hand side of the membrane and an electrical potential difference builds up across the membrane as it becomes charged
The chemical forces causing a net diffusion of K from left to right are now countered by a growing electrical force which opposes the flow of K+
• Eventually an equilibrium potential is reached where the electrical force equals the chemical (or diffusional) force and no exchange occurs
• This is the potassium equilibrium potential (EK)
14
Q
What is the Boltzmann distribution *
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15
Q
Explain the Boltzmann distribution equation
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Single particle energies * covered by rectangle
16
Q
What is the Nernst equation
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17
Q
What is caused by a change in membrane potential
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18
Q
What is meant by depolarisation and hyper polarisation of membrane potential
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19
Q
Explain the space constant *
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20
Q
What is lambda with regards to the space constant
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21
Q
What is meant by passive spread of current
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22
Q
Why is a full size action potential generated at each part of the axon even though the size of the voltage decreases
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23
Q
What is meant by myelination
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24
Q
What is meant by “all or none” when it comes to action potentials
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Frequency of action potentials = intensity of stimulus
The all-or-none law guarantees that once an action potential is generated, it is always full size (no information lost).
25
What is meant by the absolute and relative refractory period of action potentials *
The refractory period, together with the threshold, allow the coding of information as a frequency code.
This type of signaling is called frequency modulation
The size of the spikes (action potentials) is always the same, but what varies is how often they happen.
Absolute refractory period: The time during which no new action potential can be initiated, no matter how strong the stimulus. Ensures unidirectional propagation of the action potential down the axon. Occurs because During the peak and early repolarization of the action potential, voltage-gated Na⁺ channels are: Already open or Inactivated (not just closed — they cannot reopen until reset
Relative Refractory Period: A period immediately after the absolute refractory period during which a stronger-than-usual stimulus can initiate another action potential. Occurs because Some Na⁺ channels have reset (are closed but ready to open), but: K⁺ channels are still open, causing hyperpolarization.The membrane potential is more negative than resting (undershoot) → needs a larger depolarization to reach threshold. It Allows modulation of firing rate based on stimulus strength and Protects from spurious reactivation while still allowing high-frequency firing if needed.
26
Which organism is used as a model organism for the mechanism of action potentials
The squid giant axon can be up to 1 mm in diameter – a thousand times thicker than
in humans. The first recording of an action potential using a microelectrode inserted into an
axon
27
What are the phases of the action potential ( shown on a graph)
After reaching threshold gNa increases quickly, but
inactivation then reduces gNa to zero.
• gK increases more slowly, and only decreases once
the voltage has hyperpolarised.
• The absolute refractory period is when the sodium
channels are inactivated
•The relative refractory period is when gK dominates
following the action potential
28
When are Na+ and K* channels open/closed during an action potential
Voltage-gated ion channels experience activation, deactivation and inactivation during the action potential.
29
What is happening when an axon is at rest
At rest there is a small resting potassium permeability through voltage-independent leak channels.
30
What happens during the depolarisation stage of an action potential*
31
What happens during the repolarisation stage of an action potential*
A refractory period persists until the voltage gated sodium channels have recovered from inactivation.
Ionic gradients are re-established by Na/K ATPase activity.
32
How much does sodium ion conc. change by in depolarisation
33
How does an action potential propagate in the absence of a myelin sheath
34
What is saltatory conduction and how does it work *
When a stimulus reaches the axon, it triggers the opening of voltage-gated sodium channels at the first Node of Ranvier.
Sodium ions (Na⁺) flow into the neuron, causing depolarization
The depolarization at the first Node of Ranvier creates a local current that affects the adjacent section of the axon.
The current flows along the internodal regions
The current reaches the next Node of Ranvier, causing the voltage-gated sodium channels at this node to open, triggering a new depolarization
After depolarization, the voltage-gated sodium channels close, and voltage-gated potassium channels open, allowing potassium ions (K⁺) to exit the neuron, restoring the negative resting potential (repolarization).
This process also occurs in the internodal regions and at the nodes, where the action potential has been generated.
35
Where are voltage gated K channels found
36
What is the relationship between diameter and conduction of an action potential velocity
37
What is a compound action potential*
is the collective electrical response generated by a group of neurons or nerve fibers when they are simultaneously stimulated.
Size of compound action potential depends on the number of fibers activated and the diameter of the fibers
38
How can the flow of ions through a channel be studied using patch clamping *
A glass pipette with a very fine tip is used to isolate a small patch of the membrane
The pipette is gently pressed onto the membrane, and a high-resistance seal is formed between the membrane and the pipette.
A current amplifier is used to measure the flow of ions through the open ion channels. The ion flow generates an electrical current, and the amplifier records these changes in current, providing real-time data.
39
What can a whole cell patch clamp be used for and how does it work*
allows researchers to measure the ionic currents that flow through the cell membrane, investigate membrane potential
In voltage-clamp mode, the membrane potential is held constant, and the current needed to maintain that potential is measured. This allows researchers to study ion channel properties and how they respond to changes in membrane potential.
In current-clamp mode, a known current is applied, and the resulting changes in membrane potential are recorded. This mode is typically used for studying action potentials and other forms of electrical signaling in the cell.
40
What are the different kinds of stimuli that can open channels
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What different toxins can affect ion channels
42
What is the structure of voltage-gated sodium channels
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How do voltage gated Na+ channels open
As the membrane potential reaches the threshold, the voltage-sensing regions of the Na⁺ channel, located in the S4 segment of the α-subunit, are sensitive to changes in voltage.
The S4 segment contains positively charged amino acids, and when the membrane potential becomes more positive, these charges experience repulsion, causing the activation gate (a part of the α-subunit) to move.
This movement opens the channel rapidly, allowing Na⁺ ions to flow into the cell along their electrochemical gradient. This is known as channel opening.
44
How do potassium ion channels only allow potassium ions to go through*
The selectivity filter is made up of a series of carbonyl oxygens from the protein backbone that line the pore. These oxygens are positioned in such a way that they specifically interact with hydrated potassium ions (K⁺).
the selectivity filter is sized specifically to dehydrate potassium ions but not sodium ions.
The carbonyl oxygens in the selectivity filter interact with the potassium ion in such a way that it can stabilize the K⁺ ion without the need for the hydration shell. The size of the selectivity filter matches the size of K⁺ ions (after they are dehydrated) more closely than Na⁺ ions.
Sodium ions (Na⁺), which are smaller than potassium ions, cannot shed their hydration shell as easily because the carbonyl oxygens in the selectivity filter are spaced too far apart to adequately stabilize the smaller Na⁺ ion.
45
How do Voltage-gated potassium channels open/ close
This depolarization causes a conformational change in the voltage-sensing part of the potassium channel, specifically in the S4 segments (positive charge residues within the transmembrane region of the channel).
The S4 segment acts like a voltage sensor, and when the membrane potential becomes more positive, it experiences repulsion from the inside of the cell, which causes the channel's activation gate to open.
The opening of the channel allows K⁺ ions to flow out of the cell, down their concentration gradient
46
What are the types of synapses
47
How are neurotransmitters released at a synapse*
When an action potential travels down the axon of the presynaptic neuron, it reaches the axon terminal
depolarization of the membrane opens the voltage-gated calcium channels, allowing calcium ions (Ca²⁺), which are present in higher concentration outside the cell, to flow into the axon terminal.
The increase in intracellular calcium concentration triggers a series of molecular events that cause the vesicles to move toward the presynaptic membrane.
The vesicles are anchored to the membrane by proteins known as SNARE proteins (including syntaxin, SNAP-25, and synaptobrevin).
When calcium ions bind to synaptotagmin (a calcium-binding protein on the vesicle), it induces a conformational change that enables the SNARE proteins to mediate the fusion of the vesicle with the presynaptic membrane.
the neurotransmitters inside the vesicle are released into the synaptic cleft and diffuse across the synaptic cleft and bind to specific receptors on the postsynaptic membrane of the target cell
This binding triggers a response in the postsynaptic cell, either by opening ion channels (leading to depolarization or hyperpolarization) or by activating intracellular signaling pathways.
After neurotransmitter release, the signal must be terminated to prevent continuous activation of the postsynaptic cell
48
What is the life cycle of acetylcholine
Acetyl-CoA (from mitochondria)
Choline (taken up from extracellular space via high-affinity choline transporter)
Enzyme: Choline acetyltransferase (ChAT)
ACh is transported into synaptic vesicles by vesicular acetylcholine transporter (VAChT).
ACh binds to:
Nicotinic receptors (nAChRs) → ion channels (fast, excitatory)
Muscarinic receptors (mAChRs) → G-protein coupled (modulatory, slower)
ACh is rapidly degraded by acetylcholinesterase (AChE) in the synaptic cleft.
Breakdown products:
Choline
Acetate
49
What are SNAREpins needed for
Each SNARE pin releases about 35 kBT of energy (equivalent to about 20 kcal/mol) as it
zippers up. The activation energy for lipid bilayer fusion is about 50 to 100 kBT , and so
three or more individual SNAREpins suitably arranged provide enough energy to drive fusion
50
What is the process of Ca2+ dependent vesicular release
51
What could clostridial toxins do
52
Explain the knee jerk circuit*
53
What are some examples of simple neurotransmitters
54
What are the different post synaptic potentials*
are changes in the membrane potential of a postsynaptic neuron that occur in response to neurotransmitter binding to receptors on the postsynaptic membrane. These potentials can either excite or inhibit the postsynaptic neuron
Excitatory Postsynaptic Potential is a depolarizing change in the membrane potential of the postsynaptic neuron, making it more likely to reach the threshold and fire an action potential. When an excitatory neurotransmitter (e.g., glutamate) binds to its receptor, it typically opens ligand-gated ion channels that allow positively charged ions (such as Na⁺ or Ca²⁺) to flow into the postsynaptic cell.
Inhibitory Postsynaptic Potential a hyperpolarizing change in the membrane potential of the postsynaptic neuron, making it less likely to reach the threshold and generate an action potential. When an inhibitory neurotransmitter (e.g., GABA or glycine) binds to its receptor, it typically opens ligand-gated ion channels that allow negatively charged ions (such as Cl⁻) to flow into the postsynaptic cell or positively charged ions (like K⁺) to flow out.
This causes the inside of the neuron to become more negative
55
How can integration of inputs from dendrites determine if an action potential initiated at the axon hillock*
The inputs from multiple synapses are summed at the axon hillock. This summation can occur in two ways:
Spatial Summation: Multiple EPSPs and/or IPSPs from different locations on the dendrites (or different synapses) occur simultaneously. If enough excitatory signals arrive at the same time from various inputs, they can collectively reach the threshold for initiating an action potential.
Temporal Summation: Multiple EPSPs and/or IPSPs from a single synapse occur in rapid succession. If the timing is such that the depolarization from a single synapse adds up before the membrane potential has returned to baseline, the signals can cumulatively lead to reaching the threshold.
The axon hillock is the area of the neuron with the highest density of voltage-gated sodium (Na⁺) channels, making it the most likely place to generate an action potential.
56
What is the structure of the nicotinic ACh receptor
57
How can Cl- ions entering a neurone prevent an action potential from occurring
Chloride (Cl⁻) ions are negatively charged. When Cl⁻ ions enter the neuron, they increase the negative charge inside the cell (make the inside of the neuron more negative relative to the outside), leading to hyperpolarization.
This hyperpolarization is a type of inhibitory postsynaptic potential (IPSP). IPSPs move the membrane potential further away from the threshold potential (typically -55 mV), making it harder for the neuron to depolarize and fire an action potential.
58
What are the changes associated with ageing
59
What is dementia
60
What can happen as dementia progresses
61
What happens in the first stage of Alzheimer’s
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What are amyloid plaques
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What are neurofibrillary tangles
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What could amyloid plaque formation be due to
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What does early onset Alzheimer’s involve
66
How may the presence of the beta amyloid cause Alzheimer’s
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What is gamma secretase
68
What is the definition of an amyloid
An amyloid is defined as a misfolded protein that aggregates into insoluble fibrils characterized by:
β-sheet-rich structure (cross-β-sheet conformation)
69
What could be another cause of early onset Alzheimer’s
70
What are the characteristics of neurofibrillary tangles
71
What is the structure of Tau in Alzheimer’s
72
How is the protein APOE related to late onset Alzheimer’s
73
How is the protein TREM2 related to late onset Alzheimer’s
It also promotes microglia phagocytosis of protein aggregates, amyloid plaques, neuronal debris
In late Alzheimer’s, TREM2 is missing from microglia so it no longer associates with amyloid plaque. Amyloid plaque will become bigger into filamentous plaque, pTau also builds up, contributing to inflammation and neuronal failure
74
What other factors contribute to getting Alzheimer’s
75
What is the mechanism of metabolic clearance
76
What therapies are there currently for Alzheimer’s
77
Why is early detection of Alzheimer’s important
78
what are the major symptoms of Parkinson’s
79
What are the possible origins of Parkinson’s
80
What is dopamine vulnerable to
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What is the pathway of dopamine production
82
How is dopamine released*
83
What receptors does dopamine bind and what happens when it does bind
PKA phosphorylates CREB (cAMP Response Element-Binding Protein).
Phospho-CREB (pCREB) enters the nucleus and binds to CRE sequences in DNA.
This promotes the transcription of CRE-containing genes, often involved in:
Synaptic plasticity
Learning and memory
Long-term neuronal changes
84
What are the different roles of dopamine
85
What can rescue Parkinsonian rabbits
86
How do neuronal ensembles work*
87
What happens to dopamine neural ensembles in parkinsons and how can it lead to motor symptoms
In Parkinson’s no neural ensembles can be selected
Dopamine neurons selectively die
88
What are lewy bodies + link to parkinsons*
Lewy bodies are primarily made up of alpha-synuclein, a protein that normally plays a role in neurotransmitter release and synaptic function. However, in certain neurodegenerative diseases, alpha-synuclein can misfold and accumulate, forming insoluble clumps that disrupt normal cell function
These clumps accumulate within the cytoplasm of neurons, impairing their ability to function properly and leading to cell death.
The accumulation of misfolded alpha-synuclein into Lewy bodies is thought to contribute to the progressive loss of dopaminergic neurons in the brain. This process disrupts normal cell signaling, damages cellular machinery, and eventually leads to cell death.
As the disease progresses, Lewy bodies can also spread to other brain regions involved in cognition, emotion, and behavior.
89
What is alpha synuclein + link to parkinsons*
90
How does alpha synuclein aggregate
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How does alpha synuclein spread in a Parkinson patients brain
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Where could Parkinson’s start in the body
93
Explain the pathway of the aggregation of alpha synuclein and the formation of levy bodies
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How can synaptic mechanisms affected be by aggregating alpha synuclein
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How does alpha synuclein affect neurotransmission in a healthy brain vs aggregating alpha synuclein on synaptic degeneration
Healthy:
Binds to synaptic vesicle membranes.
Promotes vesicle clustering near the active zone.
Modulates SNARE complex assembly, essential for vesicle fusion and neurotransmitter exocytosis.
Helps maintain synaptic plasticity and signal precision.
Aggregated:
Interferes with vesicle docking and fusion.
Impairs SNARE complex function.
Leads to reduced neurotransmitter release, especially dopamine.
Triggers synaptic spine loss, axonal degeneration, and terminal swelling.
Misfolded α-synuclein can be released and taken up by neighboring neurons.
Acts in a prion-like fashion, promoting misfolding of native α-synuclein in healthy cells
96
What is the theoretical pathway of the progression of Parkinson’s
Temporalspatial spreading of tau-positive neurofibrillary lesions in the progression of
Alzheimer’s disease and a-synuclein-positive lesions (lewy bodies & dendrites) during
Parkinson’s disease
97
What is a prion
Prion protein can be infectious and can cross species barrier but rarely
There are different strains of prions = different phenotypes of disease
98
What is the different isoforms of the prion protein gene
99
Explain a model for the neurodeheneration caused by prions
100
How do prions and prion-like molecules (e.g. a-syn, b-amyloid, tau) spread from cell to cell? (Proposed mechanisms)
101
What are the different diseases associated with the aggregation of alpha synuclein and tau
102
What is the role of PERK
103
How can the PERK pathway be modulated
104
What are the two types of Parkinson’s
105
How do lewy bodies spread through the brain
106
How can L-DOPA be used to treat Parkinson’s + limitations
107
How can cell replacement therapy be used to treat Parkinson’s + limitations
108
How can stem cell therapy be used to treat Parkinson’s + limitations
