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The Adaptive Brain complete summary VU amsterdam

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  • October 25, 2023
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Neurons are not good conductors of electricity, but they have mechanisms that generate electrical
signals based on the flow of ions across plasma membranes.
- Rest membrane potential: negative potential on the inside
- Action potential: positive potential on the inside
Electrical signals of nerve cells
Resting membrane potential: depends on the type of neuron; mostly between -40 to -90 mV. The
resting membrane potential is the electrical potential difference measured across the membrane
(inside with respect to the outside). It is based on 2 membrane
properties: lipid bilayer is impermeable for ions and specialized ion
channels can conduct ions selectively. It is also based on 2 principles in
physics: there is diffusion of particles (high concentration → low
concentration) and there are electrical forces between electrical charges
(positive and negative attract each other, whereas +/+ and -/- repel each
other). The most important ions are K+, Na+, Ca2+ and Cl-
Neurons encode information via electrical signals that results from
changes in resting membrane potential. Types of electrical signals:
- Receptor potential (slow signal): due to activation of sensory
neurons by external stimuli (light, sound, heat, touch). Sensory
neurons send their electrical signals to the nervous system.
The larger the sensory stimulus, the larger the amplitude.
- Synaptic potential (fast signal): associated with communication
between neurons at synaptic contact. Allows transmission of
information from one neuron to another neuron.
From the nervous system it goes to the nervous system.
- Action potential (very fast signal): type of electrical signal that travels along their long axons.
It is responsible for the long-range transmission of information. It goes from the nervous
system to the motor neurons.
We can use a microelectrodes to measure the membrane potential. You use a microelectrode to
inject the current and thereby stimulate it and as a result, the microelectrode will record and
measure the membrane potential.
- Active responses: you inject a positive current, depolarization happens (Na+/Ca2+ go inside
the cell, K+ goes outside the cell → cell
contracts), this depolarization happens at
a certain level of threshold potential, so
an action potential occurs. This is the
basis of information transfer in the
nervous system.
- Passive responses: you inject a negative
current, hyperpolarization (the neuron is
insensitive to stimulus and depolarization
during this time) happens due to the small
depolarization. This happens at synapses
because they are small so they give small
currents. Inhibitory synapse gives
hyperpolarization. Active synapse gives
small depolarization.

,When there is an action potential, depolarization occurs (membrane potential becomes less
negative). Na+/Ca2+ flow inside the cell, making it more positive and K+ goes outside the cell.
Hyperpolarizing responses do not require an unique property of neurons and therefore they are
called passive electrical responses. Passive conduction decays over distance.
At rest, the neuron has a resting membrane potential (potential across the membrane). This means
that the interior of the cell is negatively charged (due to the positive K+ ions inside the cell which
attracts negative molecules). Hyperpolarization is when the membrane potential becomes more
negative at a particular spot on the neuron’s membrane, while depolarization is when the membrane
potential becomes less negative (Na+/Ca2+ flow inside the cell whereas K+ goes outside the cell).
Depolarization and hyperpolarization occur when ion channels in the membrane open or close. For
example: the opening of channels that let positive ions flow out of the cell and negative ions in to the
cell can cause hyperpolarization. Examples: opening the channels of K+ out of the cell and Cl- into the
cell. also, the opening of channels that let
positive ions flow into the cell can cause
depolarization. Example: opening of channels
that let Na+ into the cell and K+ out of the cell.
Action potentials are considered as active
responses because they are generated by
selective changes in permeability of the neuronal
membrane. Active conduction is constant over
distance.
Larger currents do not provoke larger action
potentials because of the all-or-nothing rule. The
larger the current = the higher the frequency of
action potentials (more action potential peaks
are then visible).
How ion movement produce electrical signals
Electrical potentials are generated across
membranes:
1. There is a difference in the concentration of specific ions (active transporters)
2. Membranes are selectively permeable for some ions (ion channels).
These 2 conditions depend on 2 different kinds of
proteins in the plasma membrane:
1. Active transporters (pumping stations): ion
concentration gradient is established by this.
They actively move ions into or out of the
cell against concentration gradient. Ion
transporters use ATPase pumps (Na+/K+
pump and Ca2+ pump). When the pump is
phosphorylated, Na+ is taken up and
pumped to the outside of the cell; when the
pump Is dephosphorylated, K+ is taken up
and pumped to the inside of the cell.
We have ion exchangers such as antiporters like Na+/Ca2+ or Na/H but also co-transporters
such as K+/Cl-, K+/Cl-/Na+ and Na+/neurotransmitters. These ion transporters do not require
ATP but use the potential energy from the concentration gradient of other ions as an energy

, source. One or more ions are taken up their electrical gradient, while simultaneously taken
another ion (usually Na+) down its gradient.




2. Ion channels (lock): they have a selective permeability and allow only certain kinds of ions to
cross the membrane in the direction of their concentration gradient.
- Voltage gated channels: respond to changes in membrane potential. The membrane
potential alters the conformation of the channel proteins, resulting in their opening/closing.
The channels have voltage sensors that detect potential across the membrane. → Na, K, Cl
and Ca channels.
- Ligand gated channels: respond to changed by binding of chemical signals (ligands). The
chemical signals bind to the extracellular/intracellular domains of these proteins. →
neurotransmitter receptor, acid sensing ion channel (ASICs), Ca activated K channels, cyclic
nucleotide gated channel, Gaba
- Thermosensitive channel: responds to heat
- Mechanosensitive channel: respond to stretch.
Transporters create the concentration gradient that help drive ion fluxes through open ion channels,
thereby generating electrical signals.
The main difference between ion channels and active transporters is that ion channels are involved
in the passive transportation of ions whereas active transporters are involved in the active
transportation of ions by consuming ATP. Ion channels and active transporters work together to
generate a resting membrane potential, action potential, synaptic potential and receptor potential.
Example:
1. Concentration of K+ on each side of the membrane is equal so there is no electrical potential
(no net flux of K+)
2. Concentration of K+ on the inside is higher than on the outside so the electrical potential on
the inside is negative relative to the outside (in the relaxed state, the neuron is negative;
there is a net flux of K+ from inside to the outside of the neuron). The difference in electrical
potential is generated because K+ ion flow to the outside take their electrical charge (K+; one
positive charge) with them as they go, so the inside becomes more negative.
Equilibrium will quickly be reached: the increased positive K+ outside makes the outside less
attractive to the positively charged K+. The net movement to the outside will stop when the potential
(electric) change across the membrane exactly offsets the concentration gradient. At electrochemical
equilibrium, there is a balance between 2 opposing forces:
1. Concentration gradient of K+ (amount of ions inside and outside)
2. Opposing electrical gradient that tends to stop K+ from moving across the membrane.
The number of K+ ions that need to flow to generate electrical potential is very small. This is
important because it means that the concentration of ions on each side of the membrane remains
essentially constant and tiny fluxes of ions required to establish the membrane potential do not
disrupt chemical electroneutrality of the solution on each side of the membrane (K+ vs Cl-).

, Forces that create membrane potentials
- Equilibrium potential: electrical potential generated across the membrane at
electrochemical equilibrium. It is the membrane potential where the net flow through any
open channels is 0. The number of ions that need to flow to generate the equilibrium
potential is very small, less than one millionth of the total number of K+ ions in the solutions.
When there is a balance between the diffusion force and the electrical force, there is no net
movement of K+ ions and electrochemical equilibrium is reached!
Calculating the equilibrium potential → Nernst equation (environment with only one permeant ion):
𝑹∗𝑻 𝑿𝒐𝒖𝒕
Ex = 𝒛∗𝑭 𝒙 𝑳𝒏 ( 𝑿𝒊𝒏 )

- Ex = equilibrium potential
- R = gas constant = 8.31
- T = temperature in Kelvin
- Z = valence (electrical charge) of the ion (K+ = +1, Ca2+ = +2, Cl- = -1)
- Xout= concentration outside
- Xin= concentration inside
Log 10^x = x
Log 10 = 1
Log 1 = 0
Log 1/10 = -1
Log 100/1= 2


58 1
Ex = 1
𝑥 log 10 = −58 𝑚𝑉

The reversal potential (also known
as the Nernst potential) of an ion is
the membrane potential at which
there is no net (overall) flow of that particular ion from one side of the membrane to the other side
of the membrane.
When battery makes the inside compartment more negative, there will be less K+ flux because
negative potential will tend to keep the K+ inside (no net flux of K+, when there are many negative
molecules inside the cell, K+ will remain inside the cell because +/- attract each other). When you
make the inside even more negative, there is a flux of K+ ions from the outside to the inside (the
normal state will get reached again). So in some circumstances, the electrical potential can overcome
an ion concentration gradient.
Electrochemical equilibrium in an environment with more than one permeable ion → Goldman
equation (environment with more than one permeant ion)
Vm= voltage across the membrane

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