Week 1 – The adaptive brain
Lecture 1 – Neurons generate electrical signals (Chpt. 2) – Electrical signals of nerve cells
Task neurons: Neuronal signaling => Electrical signaling: the fundamental neuronal process that
underlies all aspects of brain functioning.
Neurons: are made up out of lipids (lipid bilayer), so;
• Poor generators & conductors of electricity -> so how do neurons communicate?
= Have mechanisms to overcome these limitations: Based upon the flow of ions across the
membrane (key functioning nerve cells)
> Lipid bilayer doesn’t allow ions to pass, but certain proteins do!
Electrical signals are fundamental for brain function. Examples of electrical signals:
1) Receptor potential of sensory nerves in finger (touch). These can be recorded by applying
electrodes to your finger ⇒ Receptor potential.
> Graph: membrane potential changes because there is a flow of ions
2) Record electrical current in soma with glass electrodes. Activate axon of single synapse (ex.
hippocampal neuron) ⇒ synapse is active. Shift from -70 to -65 mV ⇒ Synaptic potential.
> Graph: stimulate one single synapse -> change potential
3) Motor neurons: stimulate in soma and record in axon that leads to the nerve ⇒ goes from - 60 to +
30 mV ⇒ Action potential = amplitude here is much bigger than that of a synaptic potential
Difference between synaptic and action potential: the threshold.
If a certain threshold is reached, an action potential occurs.
Experiments: Recording electrical signals in neurons -> culture single neurons and impale the
neurons with 2 electrodes (one adds current and one to report)
> Electrode = pieces of glass with sharp tip that can penetrate lipid bilayer
Electrodes
1) Stimulate neuron with microelectrode to inject current (stimulation electron)
2) Record this with microelectrode to measure membrane potential (record electron)
,• No stimulation: resting membrane potential = -65 mV
• Passive responses – synaptic potentials:
o Negative current injected ⇒ resting membrane potential becomes more
negative, hyperpolarization (negative deflections: nothing happens). More
current injected ⇒more negative RMP becomes.
o Positive current injected ⇒RMP increases = depolarization
• If the positive passive response increases enough so it goes over the threshold value (- 50
mV), by increasing the positive current value, an action potential will occur
(depolarization) ⇒all or none phenomena.
o How higher the current, how more action potentials: An action potential will not go
above 40 mV (amplitudes are the same), but they will multiply. So stimulus intensity is
encoded in AP frequency, not in amplitude of AP.
o Once the threshold is reached, there will always be a AP and it cannot be stopped.
Summary
• Neurons transfer information via electrical signals.
• At rest neurons have a negative potential - resting membrane potential (- 50 mV to - 90 mV;
depending on what kind of neuron).
• Injection of negative current induces hyperpolarization.
• Injection of positive current induces depolarization.
• If depolarization reaches threshold potential, an action potential is generated.
• An action potential is an all-or-none phenomenon.
What is the importance of action potentials?
• Your life depends on action potentials.
• All-or-none fashion.
• Carry information: stimulus intensity (information) is encoded in AP frequency.
• Allow long range signal transduction, because we have long neurons like motor neurons.
Synaptic potentials die off quickly if this wasn’t the case.
> Most important: APs allow long range transport of electrical signals:
• Low current injection at certain position in axon results in an increase in membrane potential.
This MP signal decays very rapidly when the distance between the injection site and recording
electrode (distal site) is increased. So when you get further away from the injection site.
o The signal cannot traffic very fast (because of the lipid bilayer) => passive transductions
decreases quite fast
o This is even the case for short axons
• When enough current is injected we get an action potential (threshold of -50 mV
, achieved). The amplitude of action potential does not decrease when you move further
away from the site of injection. The amplitude remains the same.
o This is because it’s an all-or-none phenomenon.
• Insheetment: for even longer distances myelin and nodes of Ranvier are present so
saltatory actions happen for longer transport of electrical signals.
How do ion movements produce electrical signals? (generate AP):
• At rest neurons always have a negative potential: resting
membrane potential (RMP).
• What we need:
o Plasma membrane that is impermeable to ions.
o Concentration differences of specific ions:
• Potassium (K+) high inside the cell, low outside the cell
• Sodium (Na+) high outside, low inside cell
• Chloride (Cl-) high outside, low inside cell
• Charged proteins are mostly negative charged and are mainly inside the neurons
INSIDE CEL LIPID BILAYER OUTSIDE CELL
> Ions cannot move across
> BUT proteins allow it
=> Movement of ions = create AP
Proteins in the membrane allow ion transport:
1. Active transporter = Sodium-potassium pump: creates sodium-potassium
gradient.
• Uses ATP to transport ions against their chemical gradient
• Consumes a lot of energy: 20-40 % of total brain energy, because it transports ions against
their concentration gradient.
• Pumps 2 K+-ions in, 3 Na+-ions out.
2. Ion channels = are selectively permeable to certain ions; allow membrane passage of certain ions
• They can only open and close upon changes in membrane
potential.
o If it opens: ALL the Na+ will go into the cell, ALL the K+
will go out of the cell
o Voltage gated channels
• At rest:
o K+-channels open: can leak out a little bit.
o Na+-channels closed: sodium is not allowed to enter
the cell at rest (no net flow)
, What does it mean if there is a bit of leakage?
= Diffusion and electrical forces
1) At rest K+-channels are open.
• Because K+-concentration is higher inside than outside, it
moves outside the cell = diffusion force (for equilibrium) ⇒
negative potential inside cell (relative to outside cell)
2) This change in potential is counter-acted by the electrical force ⇒ K+
is forced/pulled back into the cell
Conclusion: At rest: no net movement of K+-equilibrium potential ⇒
equilibrium constant
> These two forces result into this membrane potential (because of the tug of war no ions moving,
but there is a membrane potential!)
The Equilibrium potential can be measured with an electrochemical equilibrium: water with
semipermeable lipid membrane.
(A) No net flux of K+: inside and outside 1 mM K+.
(B) Net flux of K+ from inside to outside: 10 mM inside and 1 mM outside.
o Flux of K+ from inside to outside, balanced by opposing membrane potential: 10 mM
inside, 1 mM outside ⇒ diffusion through K+-channels ⇒ negative potential on inside
membrane ⇒ -58 mV due to concentration difference (= magical number)
Equilibrium potential for any ion:
• Nernst equation = is the equation for equilibrium of membrane potential for 1 ion
o 2 different concentrations: ions outside and ions inside
o Sodium (NA+) and pot (K+) => z = 1
o Chloride (Cl-) => z = 2
If all things are filled in => get a simplified version:
Example:
• 10 mM inside, 1 mM outside; Ex = - 58 mV = equilibrium constant K+.
• 1 mM Na+ inside, 10 mM Na+ outside; Ex = + 58 mV = equilibrium constant Na+.
But want ALL ions in the brain and the permeability of the membrane for a certain ion
= Goldman equation:
> K+ and Na+ with the permeability for theses ions
> P = permeability
Lecture 1 – Neurons generate electrical signals (Chpt. 2) – Electrical signals of nerve cells
Task neurons: Neuronal signaling => Electrical signaling: the fundamental neuronal process that
underlies all aspects of brain functioning.
Neurons: are made up out of lipids (lipid bilayer), so;
• Poor generators & conductors of electricity -> so how do neurons communicate?
= Have mechanisms to overcome these limitations: Based upon the flow of ions across the
membrane (key functioning nerve cells)
> Lipid bilayer doesn’t allow ions to pass, but certain proteins do!
Electrical signals are fundamental for brain function. Examples of electrical signals:
1) Receptor potential of sensory nerves in finger (touch). These can be recorded by applying
electrodes to your finger ⇒ Receptor potential.
> Graph: membrane potential changes because there is a flow of ions
2) Record electrical current in soma with glass electrodes. Activate axon of single synapse (ex.
hippocampal neuron) ⇒ synapse is active. Shift from -70 to -65 mV ⇒ Synaptic potential.
> Graph: stimulate one single synapse -> change potential
3) Motor neurons: stimulate in soma and record in axon that leads to the nerve ⇒ goes from - 60 to +
30 mV ⇒ Action potential = amplitude here is much bigger than that of a synaptic potential
Difference between synaptic and action potential: the threshold.
If a certain threshold is reached, an action potential occurs.
Experiments: Recording electrical signals in neurons -> culture single neurons and impale the
neurons with 2 electrodes (one adds current and one to report)
> Electrode = pieces of glass with sharp tip that can penetrate lipid bilayer
Electrodes
1) Stimulate neuron with microelectrode to inject current (stimulation electron)
2) Record this with microelectrode to measure membrane potential (record electron)
,• No stimulation: resting membrane potential = -65 mV
• Passive responses – synaptic potentials:
o Negative current injected ⇒ resting membrane potential becomes more
negative, hyperpolarization (negative deflections: nothing happens). More
current injected ⇒more negative RMP becomes.
o Positive current injected ⇒RMP increases = depolarization
• If the positive passive response increases enough so it goes over the threshold value (- 50
mV), by increasing the positive current value, an action potential will occur
(depolarization) ⇒all or none phenomena.
o How higher the current, how more action potentials: An action potential will not go
above 40 mV (amplitudes are the same), but they will multiply. So stimulus intensity is
encoded in AP frequency, not in amplitude of AP.
o Once the threshold is reached, there will always be a AP and it cannot be stopped.
Summary
• Neurons transfer information via electrical signals.
• At rest neurons have a negative potential - resting membrane potential (- 50 mV to - 90 mV;
depending on what kind of neuron).
• Injection of negative current induces hyperpolarization.
• Injection of positive current induces depolarization.
• If depolarization reaches threshold potential, an action potential is generated.
• An action potential is an all-or-none phenomenon.
What is the importance of action potentials?
• Your life depends on action potentials.
• All-or-none fashion.
• Carry information: stimulus intensity (information) is encoded in AP frequency.
• Allow long range signal transduction, because we have long neurons like motor neurons.
Synaptic potentials die off quickly if this wasn’t the case.
> Most important: APs allow long range transport of electrical signals:
• Low current injection at certain position in axon results in an increase in membrane potential.
This MP signal decays very rapidly when the distance between the injection site and recording
electrode (distal site) is increased. So when you get further away from the injection site.
o The signal cannot traffic very fast (because of the lipid bilayer) => passive transductions
decreases quite fast
o This is even the case for short axons
• When enough current is injected we get an action potential (threshold of -50 mV
, achieved). The amplitude of action potential does not decrease when you move further
away from the site of injection. The amplitude remains the same.
o This is because it’s an all-or-none phenomenon.
• Insheetment: for even longer distances myelin and nodes of Ranvier are present so
saltatory actions happen for longer transport of electrical signals.
How do ion movements produce electrical signals? (generate AP):
• At rest neurons always have a negative potential: resting
membrane potential (RMP).
• What we need:
o Plasma membrane that is impermeable to ions.
o Concentration differences of specific ions:
• Potassium (K+) high inside the cell, low outside the cell
• Sodium (Na+) high outside, low inside cell
• Chloride (Cl-) high outside, low inside cell
• Charged proteins are mostly negative charged and are mainly inside the neurons
INSIDE CEL LIPID BILAYER OUTSIDE CELL
> Ions cannot move across
> BUT proteins allow it
=> Movement of ions = create AP
Proteins in the membrane allow ion transport:
1. Active transporter = Sodium-potassium pump: creates sodium-potassium
gradient.
• Uses ATP to transport ions against their chemical gradient
• Consumes a lot of energy: 20-40 % of total brain energy, because it transports ions against
their concentration gradient.
• Pumps 2 K+-ions in, 3 Na+-ions out.
2. Ion channels = are selectively permeable to certain ions; allow membrane passage of certain ions
• They can only open and close upon changes in membrane
potential.
o If it opens: ALL the Na+ will go into the cell, ALL the K+
will go out of the cell
o Voltage gated channels
• At rest:
o K+-channels open: can leak out a little bit.
o Na+-channels closed: sodium is not allowed to enter
the cell at rest (no net flow)
, What does it mean if there is a bit of leakage?
= Diffusion and electrical forces
1) At rest K+-channels are open.
• Because K+-concentration is higher inside than outside, it
moves outside the cell = diffusion force (for equilibrium) ⇒
negative potential inside cell (relative to outside cell)
2) This change in potential is counter-acted by the electrical force ⇒ K+
is forced/pulled back into the cell
Conclusion: At rest: no net movement of K+-equilibrium potential ⇒
equilibrium constant
> These two forces result into this membrane potential (because of the tug of war no ions moving,
but there is a membrane potential!)
The Equilibrium potential can be measured with an electrochemical equilibrium: water with
semipermeable lipid membrane.
(A) No net flux of K+: inside and outside 1 mM K+.
(B) Net flux of K+ from inside to outside: 10 mM inside and 1 mM outside.
o Flux of K+ from inside to outside, balanced by opposing membrane potential: 10 mM
inside, 1 mM outside ⇒ diffusion through K+-channels ⇒ negative potential on inside
membrane ⇒ -58 mV due to concentration difference (= magical number)
Equilibrium potential for any ion:
• Nernst equation = is the equation for equilibrium of membrane potential for 1 ion
o 2 different concentrations: ions outside and ions inside
o Sodium (NA+) and pot (K+) => z = 1
o Chloride (Cl-) => z = 2
If all things are filled in => get a simplified version:
Example:
• 10 mM inside, 1 mM outside; Ex = - 58 mV = equilibrium constant K+.
• 1 mM Na+ inside, 10 mM Na+ outside; Ex = + 58 mV = equilibrium constant Na+.
But want ALL ions in the brain and the permeability of the membrane for a certain ion
= Goldman equation:
> K+ and Na+ with the permeability for theses ions
> P = permeability
