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Summary The Adaptive Brain
- Instelling
- Vrije Universiteit Amsterdam (VU)
The Adaptive Brain
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Chapter 2-4 Tuesday, 1 November 2022Electrical Signals of Nerve Cells
Neurons communicatie through electrical signalling, which si a process that underlies all
aspects of brain functioning. Neurons are poor generators and conductors of electricity.
However, they developed a mechanism to overcome this limitation based upon the flow of
ions across the membrane
Electrical signals are fundamental for brain function. Micro-electrodes are able to record 3
different electrical signals
1. Receptor potentials in skin touch receptors
2. Synaptic potential upon activation in a single synapse
3. Action potential when threshold potential is reached
Experiment - Recording electrical signals in neurons:
One electrode is inserted to stimulate the neuron, and the other to measure the
membrane potential.
A negative current is injected in the neuron which induces hyperpolarization. When the
injection is stopped, the hyperpolarization stops and balance reoccurs as the current
goes up.
Then positive current is injected, which induces depolarisation. When the positive passive
response is high enough, the threshold is reached and action potential occurs.
This process is based on All or Nothing. When the current is more increased, action
potential increase in amount
So, neurons transfer information via electrical signals. At rest, neurons have a negative
resting membrane potential. The injection of a negative current induces hyperpolarization,
whereas injection of positive current induces depolarisation. If the depolarisation reaches
threshold potential, an action potential is generated. The action potential is an all-or-none
phenomenon
Action potentials allow for a long range of transport of electrical signals. Action potential
conduction requires both active and passive current flow. Active current flows over the
membrane through the ion channels, whereas passive current flows along the axon.
Depolarisation opens Na+ channels locally and produces an action potential at point A of
the axon. The inward current flows passively along the axon and depolarises the adjacent
region at point B of the axon. This opens Na+ channels at point B, initiating action potential
here and additional inward current that passively flows along the axis to point C. As the
action potential spreads, the membrane potential repolarizes as K+ channels open and Na+
channels are inactivated. This leads to a refractory period to prevent backwards
propagation.
ION MOVEMENTS
Ion movements can produce electrical signals because of multiple reasons. First, the
plasma membrane in impermeable to ions. Second, there are multiple concentration
differences of specific ions. There is a high [K+] on the inside and a high [Na+] on the
outside
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,Chapter 2-4 Tuesday, 1 November 2022
Active transporters create ion gradients. Active transportes actively move selected ions
against the concentration gradient, and is creates ion concentration gradients. During
active transport 2K+ enter and 3Na+ exit, and this consumes around 20-40% of brain
energy
Ion channels allow ions to diffuse down the concentration gradient. Also, they are
selectively permeable to certain ions. Ion channels open and close upon changes in the
membrane potential.
Membranes are selectively permeable to ions. At rest, K+ channels are open, whereas Na+
are naturally closed. This allows K+ to move in and out, whereas the Na+ ions aren’t able to
cross the membrane
At rest, there is a diffusion force and eventually electrical force. Due to diffusion force, K+
diffuses outside of the membrane, causing a negative potential inside. This induces an
electrical force, which pulls the positive K+ back into the cell in order to prevent K+ leakage
and to remain ionic balance. So, at rest there is no net movement of K+
EQUILIBRIUM POTENTIAL AND RESTING POTENTIAL
In electrochemical equilibrium, the rate of diffusion and electrical force is equal, which
results in no net movement of the ions and therefore a balance between both forces. The
number of ions that need to flow to generate the equilibrium potential is very small, less
than 1 millionth of the total number of K+ ions in the solution. This allows the solution
concentration to be quite stable to avoid major disturbances.
Ex = (R*T/z*F) * ln [Xout]/[Xin]
Ex = equilibrium potential Xout = concentration outside
R = gas constant = 8.31 J K/Mol F = constant of Faraday = 96485 C/Mol
T = temperature (K) z= valence (charge) of ions
Xin = concentration inside
At room temperature (20 degrees Celsius)
Ex = 58/z * log [Xout]/[Xin]
Log10^x = x Log1 = 0
Log10 = 1 Log0.1 = -1
Log100 = 2
More ions —> Goldman equation
Ex = (R*T/z*F) * ln [Xout]/[Xin] per ion and adding
Resting membrane potential does not equal -58 mV as the cell consists of more ions than
KCl. It is a combined chemical energy of different ions at different concentration inside and
outside of the cll. For each ion, channels exist in the membrane that selectively conduct
that ion. The resting membrane potential can be calculated by the Goldman equation,
which is an extended Nernst equation (58*log Px*[Xout]/Px*[Xin] + …….)
• Px = permeability of the membrane for ion x
• K -> out/in
• Na -> out/in
• Cl -> in/out
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,Chapter 2-4 Tuesday, 1 November 2022
VOLTAGE CLAMP MEASUREMENTS
The voltage clamp is responsible
for the measurement of voltage-
induce currents. The current clamp
is responsible for the
measurements of current-induced
changes in membrane potential.
This method is used to stimulate
and record at the same time.
However, the pathways have to be
isolated as it does not work
otherwise.
The first current is inward fast and short-lived, whereas the second current is outward slow
and lasting. The early current depends on Na+ ions, but K+ ions are also involved
1. Early influx of Na+ —> inward current
2. Delayed efflux of K+ —> outward current
Patch clamp
A path of the neutron membrane is clamped and electrically isolated, from which currency
measures can be taken. This patch of membrane could include an ions channel, which
allow currency differences to be measured.
Microscopic Na+ currents add up to the macroscopic action potential (15pA = 1 trillionth of
household current). Macroscopic current result from the opening of several ion channels
After an action potential Na channels are inactivated and need to recover to be available for
the next action potential. This time Frame of recovery is known as the refractory period.
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, Chapter 5 Thursday, 3 November 2022
Synaptic Transmission
SYNAPSES
The synapse is the contact point between
two neurones. There are electrical and
chemical synapses.
An electrical synapse is the direct
exchange of ions and small molecules by
passive flow between the re- and
postsynaptic cell. This occurs via direct
connection between the cytosol of both
cells. The electrical synapse is extremely
fast and can go in both directions. It is a
one to one transmission and it is used for
exchange of cells in a network and fast
responses without plasticity. The currency
flows at the gap junction through pores
also known as the connexions. The
electrical synapse is used to synchronise the activity of populations of neurons
The chemical synapse is used for action potential. It is an indirect transmission of electrical
signals through chemical signalling molecules, like neurotransmitters. A chemical synapse
is less reliable for signal transport, and therefore is does not work in a 1:1 ratio. This means
not every signal develops an action potential. The chemical synapse is also fast, but slower
than the electrical. It is mostly one-directional, has tuneable transmission, and uses a vert
of neurotransmitters, it is used for regulated activity, and for plasticity functions like learning
and memory.
In the chemical synapse, there is depolarisation which open the calcium voltage-acted
channels. This allows the neurotransmitter to be released into the synaptic cleft (~20mm
space between pre and post terminal) via intravasation. After, the neurotransmitter
receptors are activated due to application of transmitter agonist or antagonist. The
chemical synapse is used for plasticity. Plasticity allows amplification and suppression of
signals, but also alteration of signals. Alteration of signals includes an electrical signal being
translated to gene transcription or phosphorylation. This can allow a long-term memory
(‘core-memories’)
NEUROTRANSMITTERS AND VESICLES
Neurotransmitters are present in the presynaptic neuron and are released upon arrival of AP
in a Ca2+ dependent manner. Specific receptors are present on the postsynaptic cells,
which can bind to more than 100 different neurotransmitters. Neurotransmitters are divided
in two main groups and are transported in 2 types ofvesicles
1. Small-molecule neurotransmitters (40-60mm) —> GABA, glutamate
- Small molecules - Found in synapses
- Local recycling. - Rapid action
- Stored in synaptic vesicles
2. Neuropeptides (60-120mm) —> packaged in vesicles and be released to activate
post synaptic receptors.
- Peptides. - Found everywhere
- Produced at the Golgi - Slow action
- Stored in dense core vesicles
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