In this lesson, we explore the nervous system and share notes as part of the study guide series. We will explore the awesome brain and nerves! Topics include Neuronal Synapses, Structure of Synapses, Types of Neurotransmitters: Glutamate vs GABA vs Glycine vs Acetylcholine vs Catecholamine, Neurotransmitter Mechanism of Action, Release, Removal, and Neuroplasticity.
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- Recall, synapses are the junction between a neuron’s axon terminal(s) and the target cell.
- Chemical synapses have a gap b/n the neuron’s axon and target. Neurotransmitters are used.
- Electrical synapses are when the axon terminal and target cell are physically connected. Gap junctions allow ions to flow between them. (These are fairly rare in humans)
- A typical neuron receives up to thousands of signals from other neurons. These synapses most often occur at the dendrites (part of the reason they’re branched is to increase surface area for synapses).
- However, there can also be synapses on the soma or the axon (usually the axon terminals)
- In the central nervous system, end feet of astrocytes cover most of the synapses.
- Synaptic cleft = gap between axon terminal and target cell
- It is bordered by the pre-synaptic membrane (of the axon terminal) and post-synaptic membrane (of the target cell)
- Just on the inside of the pre-synaptic membrane are synaptic vesicles, bubble-like structures that are full of neurotransmitters.
- The pre-synaptic axon terminal also has voltage-gated calcium channels that allow Ca2+ in.
- On the post-synaptic membrane are receptors that are specific for the neurotransmitters.
- A protein known as complexin acts like a brake, and stop the vesicles from fusing into the membrane and releasing their contents [remember: complexin complicates the process of vesicle fusion]
- The vesicle protein synaptotagmin can bind and release complexin in the presence of calcium
- As the action potential travels down the axon, positive ions continue to flood the cell. Eventually, this influx reaches the very end of the neuron – the axon terminal. When this happens, the membrane potential of the axon terminal is depolarized.
- This opens the Ca2+ to channels at the axon terminal; and calcium flows into the axon (because/c of its diffusion gradient)
- The calcium ions can then activate synaptotagmin to release the brake, and the vesicles fuse with the cell membrane, and the vesicle contents (neurotransmitters) are released into the synaptic cleft.
- Neurotransmitter then diffuses across the cleft and binds to receptors on the target cell.
- An increased frequency of axon potentials reaching the terminal causes increased opening of Ca2+ voltage gated ion channels. This causes more Ca2+ to enter the cell, which means more synaptic vesicles fuse and more neurotransmitter is released.
- Increased duration of axon potential means neurotransmitter is released for a longer duration.
- These two things (frequency & duration) affect how much neurotransmitter is in the synaptic cleft for how long, which in turn affects the cell it is firing on.
- When the train of action potentials stops firing, voltage-gated ion channels will close, Ca2+ will stop entering cell, and Ca2+ will start to exit via usual methods; neurotransmitter will stop being released.
Action potentials determine how much information is released into the synaptic cleft.
Action potentials also determine how long information is present in the synaptic cleft.
Action potentials open voltage gated calcium channels, which results in calcium flowing into the axon terminal.
Action potentials do not result in calcium leaving the target cell at the post synaptic membrane.
Types of Neurotransmitters:
- Neurons tend to have just one type of neurotransmitter that they release, but many neurotransmitters can bind to multiple types receptors.
Amino Acid Neurotransmitters:
- Have an amino group and carboxylic acid group.
- Glutamate — most common excitatory neurotransmitter of the nervous system
- GABA and Glycine — most common inhibitory neurotransmitters of the nervous system.
- GABA the most common inhibitory neurotransmitter in brain
- Glycine is most common in spinal cord
- Glycine is the most common inhibitory neurotransmitter in the spinal cord
- Glutamate is the most common excitatory neurotransmitter in the nervous system.
- Gamma-aminobutyric acid, or GABA, is the most common inhibitory neurotransmitter in the brain.
- These AA neurotransmitters are involved in most processes of the nervous system
- Peptides are polymers of amino acids; they’re much larger than other types of other neurotransmitters
- One group of peptide neurotransmitters are called the opiods. (ex: endorphin)
- These play a big role in our perception of pain, and thus those types of neurotransmitters are a target for many pain meds.
Monoamine Neurotransmitters (aka biogenic amines):
- Organic molecules with an amino group connected to an aromatic group by a 2-carbon chain.
- Serotonin, Histamine, Dopamine, Epinephrine, and Norepinephrine
- Three monoamines (dopamine, epinephrine, norepinephrine) are specifically called catecholamines; they have a catechole group (benzene + two hydroxyl groups)
- Are involved in many processes, especially in the brain; including process of consciousness, attention, cognition and emotion
- Norepinephrine in particular is released by some autonomic neurons in the PNS
- Many disorders of the nervous system involve abnormalities of the monoamine transmitters; and thus they are often a target for drugs.
- Acetylcholine — one of the most important nervous system that is not a monoamine or peptide.
- Performs a number of functions in the brain of the CNS
- In the PNS, this is released by most neurons in autonomic nervous system, and by motor neurons.
Types of Neurotransmitter Receptors:
- Combination of neurotransmitter released and receptor on post-synaptic membrane that determines whether a signal to the target cell is excitatory or inhibitory
- Many neurotransmitters can bind to multiple types of receptors; some cause excitatory response and others cause inhibitory response.
- When the target cell is another neuron, excitatory or inhibitory synapses can be scattered all over the neuron, or there are many neurons where the dendrites receive predominately excitatory synapses and the soma receives inhibitory synapses at the soma. And when the synapse happens on another neuron’s axon terminal, there’s a mix of excitatory and inhibitory synapses.
- This allows fine-tuning of neuron output at multiple levels, from the dendrite to soma to the axon terminals.
- Two major types of neurotransmitter receptors:
- Ionotropic — ligated gated ion channels. When the ligand (neurotransmitter) binds to the receptor, they open and let certain ions pass through.
- These ionotopic receptors cause graded potentials (brief, local) when they open.
- Excitatory response is usually caused in target cell if the ionotropic ion channel allows Na+ or Ca2+ in (because their positive charges cause depolarization)
- Inhibitory response is usually caused in the target cell if the ionotopic ion channel allows Cl_ or K+ ions to pass. (Cl goes in to the already negative cell; K+ travels out)
- Metabotropic — When neurotransmitter binds, it activates second messengers inside the neuron
- Second messengers can open ion channels, change protein activity, or affect gene transcription.
- When metabotropic receptors are activated, the response is slower than with ionotropic ones, but the overall effect may be larger and more widespread because of the amplification that secondary messengers can cause.
- Overall response of target cell after a metabotropic receptor binds a neurotransmitter may be brief, or it may affect the cell permanently.
- Ionotropic — ligated gated ion channels. When the ligand (neurotransmitter) binds to the receptor, they open and let certain ions pass through.
- Metabotropic neurotransmitter receptors move more slowly than ionotropic neurotransmitter receptors. Metabotropic neurotransmitter receptors move more slowly than ionotropic receptors, but their results may be larger and more widespread.
- Ionotropic neurotransmitter receptors are the type of receptor that directly allows ions to pass through the membranes.
- Metabotropic neurotransmitter receptors are the type of receptor that activate a second messenger inside the neuron.
- As action potentials travel down axons, the information they contain is really contained in the frequency of firing and duration of the chains of axon potentials.
- When the action potential reaches the axon terminal, neurotransmitter is released to bind to receptors on target cell. Eventually, it needs to be removed from the receptors and from the synaptic cleft:
- If neurotransmitter lingers in the synaptic cleft, it will mostly continue to bind to the receptor, and the duration of the trains of action potential signals won’t be able to be transmitted.
- The synapse will not be functional.
- Structure of neurotransmitter may be changed before it’s removed, so that it is not recognized by the receptor. Ex: acetylcholine (in motor neurons) is deactivated by acetylcholinesterase, which is an enzyme that breaks down acetylcholine into choline and acetate.
- Neurotransmitter removal canbe by diffusion — leftover neurotransmitter just passively diffuses out of the synapse. This only works action potentials are firing slowly.
- If action potentials are firing quickly, the rate of neurotransmitter release may be greater than the rate at which neurotransmitters can diffuse.
- Neurotransmitter removal can also be active:
(1) Enzymes break down the neurotransmitter
in the synapse into its component parts
(2) Reuptake pumps — some pre-synaptic
membranes contain special active transport
channels that actively pump neurotransmitters
back into the axon, where it can be recycled &
used in future releases.
(3) Astrocyte end-feet — in CNS, astrocytes
put their end feet all over synapses. The end
feet also contain pumps/channels that actively
pump the neurotransmitter out of synapse and into the astrocyte.
- Sometimes the neurotransmitter will be broken down or used in the astrocyte, or parts of it may be transferred by the astrocyte back to the axon terminal of the neuron so it can be recycled.
- All these methods allow the synapse to be rapidly turned on and off, so it can convey more information from neuron to target cell.
- When the structure of a neurotransmitter is changed, it is not recognized by the receptor.
Acetylcholine is deactivated by acetylcholinesterase, which is an enzyme that breaks down acetylcholine into choline and acetate.
- Neuroplasticity refers to how the nervous system changes in response to experience.
- Nervous system is constantly changing (e.g. when we form new memories).
- This involves changes in synapses and/or other parts of neurons that affect how information is processed and transmitted int he nervous system
- Potentiation — increase in the strength of info flowing through a particular part of the nervous system
- Each action potential has a larger effect on target cell
- Happens with parts of neurons and chains of neurons that are used often; they grow stronger
- Depression — decrease in the strength of info flowing through a particular part of the nervous system
- Each action potential has less of an effect on target cell
- Happens with parts of neurons and chains of neurons that are used rarely; they grow weaker
- Amount of neuroplasticity is highest when the nervous system is developing (and lower afterward), but it’s present throughout life. Also increases transiently in response to nervous system injury.
Synaptic neuroplasticity — neuroplasticity changes that happen at the synapse
- Potentiation changes from lots of activity: increase in target cell response for each action potential
- For each action potential reaching the axon terminal, more neurotransmitter may be released in the synapse, so a bigger response is seen in the target cell.
- May be an increase in the number or type of membrane receptors in the post-synaptic membrane, or in the responses that occur through second messengers so that for any given amount of neurotransmitter released from the axon, the target cell has a bigger response because it is more sensitive to that neurotransmitter
- Seems like there’s communication going from axon terminal to post-synaptic membrane and backwards… details haven’t been figured out yet.
- Depression changes from inactivity: decrease in target cell response for each action potential
- For each action potential reaching the axon terminal, less neurotransmitter may be released in the synapse, so a lower / depressed response is seen in the target cell.
- Neurotransmitter receptors may decrease in number, or change type to a less responsive receptor; or there may be changes in the response of second messengers such that they elicit a weaker response than they used to.
Structural neuroplasticity — neuroplasticity changes that happen at the level of an entire cell, where the total number of synapses between a neuron and its target cell are changed.
- If two neurons are firing together frequently (one often stimulated by the other), we may see an increase in the number of synapses between pre-synaptic neuron and post-synaptic neuron
- Dendrites may get longer or growing more branches; dendritic tree becomes more complex
- Pre-synaptic neuron may sprout more axon branches and terminals so it forms more synaptic connections with dendritic tree.
- If two neurons are not firing together very frequently, we may see a decrease in the number of synapses between pre-synaptic neuron and post-synaptic neuron
- Dendrites may get shorter or lose branches, such that the dendritic tree becomes simpler
- Pre-synaptic neuron may lose some of its axon terminals.
- If this neuron is not firing very often at all, we might even lose the whole neuron:
- Pruning — process of losing neurons or parts of neurons because they’re not very active
- Potentiation and depression can happen over a wide spectrum of time.. We often categorize it into short term changes (over the course of seconds or minutes) or long term (over months or years).
- Synaptic neuroplasticity can contribute to both short term & long term potentiation and depression
- Structural neuroplasticity tends to be more associated with long term potentiation and depression
- By changing the strength of information flow between individual synapses or the between cells by changing the total number of synapses, neuroplasticity plays a very important role in the development of the nervous system as it’s wiring itself together based on the experience it’s receiving during its formative time.
- Neuroplasticity also plays a huge role in memory and learning, as well as recovery from injury to the nervous system
Depression refers to neuroplasticity that results in activity and response growing weaker.
Potentiation refers to neuroplasticity that activity and response growing stronger.
Synaptic refers to neuroplasticity that occurs at a synapse.
Structural refers to neuroplasticity that affects whole neurons or groups of neurons.
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