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Neurochemistry summary
- Instelling
- Universiteit Leiden (UL)
Summary of all the neurochemistry lectures (Brain and Cognition minor)
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NEUROCHEMISTRY SUMMARYINTRODUCTION TO NEUROCHEMISTRY
The neuron consists of three major sections: soma (cell body), dendrites (input) and axons(output). The
dendrites and axons together are called neurites.
There are three classifications (types) of neurons. They work collectively to transport information from the
senses to the brain, process the information and generate motor reactions through the muscles. (Senses –
brain – muscle). The majority of the brain consists of interneurons, sophisticated processing on information.
1. Sensory neurons
2. Interneuron
3. Motor neuron
ACTION POTENTIALS
Neurons communicate and pass messages through electrical communication which happens within the
neurons. The neurons have an excitable membrane that is negatively charged (membrane potential). When
the membrane potential is elevated above a threshold, an all or nothing response will be triggered, and the
electrical signal travels along the cell membrane without attenuation.
Resting membrane potential: Outside of the cell is more positive than inside the cell, with a voltage difference
around 65mV. At equilibrium an equal number of potassium (K+) enters and leaves the cell. The resting
potential is maintained due to an equilibrium, an equal number of potassium (K+) that enters and leaves the
cell.
Action potential: When a neuron gets excited, channels open on the membrane and sodium (Na+) ions will
enter into the cell. Because sodium is positively charged, when it starts entering the cell, more potassium
channels open and more positively charged ions enter the cell, causing the membrane potential to increase,
leading to an action potential. After the peak is reached, the cell starts to push out the positively charged ions
to restore the resting membrane potential. It then proceeds to overcompensate, causing the membrane
potential to reach a lower voltage before it restores the resting membrane potential.
1. Threshold reached (due to electrical effect of receptors through multiple other neurons)
2. Sodium (Na+) channels open and potassium channels open (K+)
3. Sodium channels close and potassium flows out due to charge difference
4. Potassium channels close, restoring equilibrium
The sodium channels are extremely important for the generation of action potentials (blocking sodium
channels can be lethal).
Absolute refractory period and relative refractory period.
ACTION POTENTIALS THROUGH THE AXON
The action potential travels along the axon. The neighbouring area of the axon gets depolarized enough to
generate an action potential that will continue traveling along the axon. This would be relatively slow, and
myelin sheaths (fatty tissue) surrounding the axon can make the distribution of the action potential faster.
Thanks to these myelin sheaths, the action potential only needs to travel between the myelin gaps (Nods of
Ranvier). In patients with multiple sclerosis, the myelin sheaths degenerate and conductance and transmission
of the action potentials is slower, which creates problems.
,Within the neuron, electrical conduction leads to action potential spreading, and between neurons this
electrical conduction needs to be transported (either chemically or electrically) to ensure neurotransmission.
SYNAPSE
Synapse is the junction between presynaptic terminals and postsynaptic membranes of the ‘next’ neuron. If
the synaptic cleft is small enough then electrical transmission is possible, otherwise the electrical signal needs
to be translated into a chemical signal.
The synapse has three main parts:
1. Presynaptic membrane (part of the axon)
2. Synaptic cleft (30nm in chemical synapses and 3nm in electrical synapses)
3. Postsynaptic membrane (mostly on the dendrites but not always). A synapse can project in multiple
different locations.
NEUROTRANSMITTERS
Neurotransmitters are released for chemical communication between neurons. The presynaptic axon terminal
controls the synaptic vesicles (containing the neurotransmitter neurons). These vesicles are placed in the
presynaptic active zones. The postsynaptic dendrites contain receptors for these neurotransmitters.
When an action potential has successfully travelled along the axon to the axon terminal, it induces release of
neurotransmitters in the presynaptic membrane. The neurotransmitters are then diffused across the synaptic
cleft. These neurotransmitters have to reach the postsynaptic membrane and trigger some response there in
order for the postsynaptic neuron to be sufficiently stimulated and pass the message on.
CHEMICAL SYNAPTIC TRANSMISSION
The neurotransmitter needs to be synthesized and stored in the vesicles of the presynaptic neuron, ready to be
released.
Different neurotransmitters are synthesized in different ways. Synthesizing enzymes for amino acid and amine
neurotransmitters are created in the soma and transported to the axon terminal. These can directly synthesize
the neurotransmitter in the axon terminal. Transporter proteins are the ones responsible for directing the
neurotransmitters into the vesicles.
Exocytosis (leaving the cell, vesicle and membrane fuse): When the action potential arrives at the axon
terminal it causes a depolarization of the terminal membrane. The vesicles are placed near the presynaptic
membrane and the depolarization will cause voltage-gated Ca+ channels to open in the active zone. The Ca+
will elevate the local level. The vesicle will then be released from the membrane causing an endocytosis,
where the membrane material can be recycled or refilled.
RECEPTORS
Neurotransmitters are released into the synaptic cleft affecting the postsynaptic neuron. They bind to receptor
proteins that are embedded in the postsynaptic density. Lock and key: the receptors are responding to specific
neurotransmitters. Neurotransmitter binding changes the receptor protein.
There are two major classes of receptors for chemical synaptic transmission:
, 1. Ionotropic: transmitter-gated ion channels. This consists of subunits that create a tubelike structure.
When they bind with a neurotransmitter, the pore opens by twisting its subunits. Ionotropic receptors
are used for fast transmission, mediated by amino-acid and amine neurotransmitters.
2. Metabotropic: G-protein-coupled receptors. These receptors trigger a cascade of other actions inside
the postsynaptic cell. They typically change the ion channels or influence cell’s metabolic activity.
Three steps are involved in this process:
- Neurotransmitter binds to the receptor protein.
- Receptor protein activates small g-protein along intercellular face of the postsynaptic membrane.
- The activated g-proteins can activate other ‘effector’ proteins which can trigger ion channels to
open, stimulate neurotransmitter synthesis.
This is a slower process, allowing for complicated responses.
EXCITATION AND INHIBITION
When there is a binding of a neurotransmitter onto a receptor, changes happen in the postsynaptic potential
(PSP). The size of these changes depends on the quantity of the transmitter. The direction of change depends
on both the neurotransmitter and the postsynaptic receptor.
- Excitatory postsynaptic potential (EPSP): postsynaptic neuron becomes active (excitatory
neurotransmitters such as glutamate). Postsynaptic membranes have sodium channels (Na+) and sodium
influx can lead to depolarization.
- Inhibitory postsynaptic potential (IPSP): postsynaptic neuron is inhibited (inhibitory neurotransmitters
such as GABA). Postsynaptic membranes have chloride channels (Cl-) and chloride influx can lead to
hyperpolarization.
REUPTAKE AND DEGRADATION
Neurotransmitter can be recycled and absorbed back into the presynaptic neuron. Blocking the reuptake of
neurotransmitters leaves neurotransmitter levels in the synapse high, thus the postsynaptic response will also
remain high. This method is used as treatment for multiple psychiatric disorders (SSRIs).
Some neurotransmitter is broken down instead of being reabsorbed. There are enzymes that break down
neurotransmitter molecules, so that the synaptic cleft is not constantly flooded with neurotransmitters. If
there was no degradation, the postsynaptic neuron would always be active and the meaning of the signal
would be lost.
DRUGS
Psychoactive drugs: these affect the nervous system to alter mood, emotion and thought:
- Increase/decrease the release of neurotransmitters
- Stimulate/block receptor sites
- Block reuptake
These drugs can either be agonists (enhancing transmitter function) or antagonists (block transmitter
function).
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