NBL355 Exam III - 16-19

What is fast axonal transport?

Move neuropeptides at a rate of 50-400 mm/day, depending on size and charge of the molecule, via motor proteins and microtubules.

Neurons are often named for what?

Neurons are named for the neurotransmitter they release ie glutametergic neurons.

What are the specific mechanisms that keep the intracellular Ca2+ levels low in a neuron?

Sodium driven calcium exchanger and calcium pumps in the plasma membrane move calcium ions out of the cell. Calcium pumps and cotransporters (H/Ca) on the membrane of the endoplasmic reticulum and mitochondria move calcium in organelles to be stores. Calcium binding proteins also lower the concentration.

How are small molecule neurotransmitters synthesized?

Synaptic endosome produce synaptic vesicles; at the pre-synaptic terminus they are filled with neurotransmitters.

What is the vesicular transporter for acetylcholine?

Synaptic vesicles

How are synaptic vesicles and dense core/secretory vesicles similar and different with respect to their biosynthesis, location, release and function?

Synaptic vesicles are made and packaged in the presynaptic terminus. They hold small neurotransmitters and are released at active zones at low calcium levels. Dense core granules are made in the soma, transported to the terminus, and released at distant sites when calcium levels are at a medium-high level.

Compare and contrast small synaptic vesicles and large secretory vesicles.

Synaptic vesicles contain neurotransmitters; they are synthesized at the aaxon terminal and released at the active zones following at low frequency stimulation of calcium influx. Secretory vesicles contain neuropeptides. They are synthesized in the cell body and moved dwon the axon. They are released at distant sites outside of the active zone and require a high frequency stimulation of calcium influx.

What are all the transmembrane proteins found on synaptic vesicles that are required for neurotransmitter uptake and release?

Synaptobrevin and synaptotagmin attach to proteins on the plasma membrane to be released.

What are SNARE proteins and where are they found?

Synaptobrevin is the vSNARE located on the vessicle membrane and binds to tSNARE proteins located on the plasma membrane. Dock the vesicle to the plasma membrane.

In general, how and where are small molecule transmitters synthesized and packaged/filled?

Synthesized in the cell body on soluble polyribosomes and transported via slow axonal transport down to the presynaptic terminus to be packages into vesicles.

In general, how and where are neuropeptides synthesized and packaged?

Synthesized in the endoplasmic reticulum and the golgi. Packaged into large core granules in the cell body and transported via fast axonal transport to the presynaptic terminus.

What is the first substrate in serotonin biosynthesis?

TRYPTOPHAN HYDROXYLASE changes tryptophan into serotonin.

What is the first substrate in catecholamine biosynthesis?

TYROSINE HYDROXYLASE turns tyrosine into dopa -- adds OH group. DOPA DECARBOXYLASE turns dopa into dopamine -- removes COO- group. DOPAMINE BETA-OXIDASE turns dopamine into norepinephrine -- removes CH2 group. Norepinephrine is turned into epinephrine by removing a NH3+ group.

What do neurons communicate with?

Target cells, which can be either other neurons or soma cells such as muscle cells or glands.

What are the two steps in which the action potential, an electrical signal, is converted into a chemical signal at the synaptic cleft?

The action potential is converted to a calcium signal. Then the calcium signal is converted to a neurotransmitter signal. And the neurotransmitter signal is converted into graded potentials.

What is the Ca++ sensor for neurotransmitter release and where is it found?

The calcium sensor is synaptotagmin and it is found on the vesicle membrane. Induces vesicle fusion to the membrane once calcium binds.

What happens when the action potential arrives at the presynaptic terminus?

The membrane depolarizes, opening voltage-gated calcium channels. Influx of calcium triggers the synaptic vesicles to fuse with the membrane and release neurotransmitters into the synaptic cleft.

What is one limitation of electrical synapses?

The post response is never larger than the pre depolarization because sodium ions diffuse, meaning the response cannot be changed or enhanced ie it is not plastic.

How do chemical synapses function?

The rapid release of neurotransmitters triggered by the action potential into the synaptic cleft induces an electrical response in the post-synaptic cell.

What is the role of the action potential in synaptic transmission? (Think both presynaptically and postsynaptically)

The role of the action potential is to depolarize the membrane to release neurotransmitters that stimulate the postsynaptic cell to elicit a response.

What does quantal mean?

The smallest amount of many forms of energy; in this case neurotransmitters; amount varies in steps.

What happens to the synaptic vesicle transmembrane proteins and lipids after exocytosis?

The synaptic vesicle becomes apart of the plasma membrane after exocytosis. A new vesicle is retrieved by endocytosis. The proteins and lipids become translocated.

How are neurotransmitters released from synaptic vesicles?

The vesicle docks to the membrane, is primed, and then calcium release at the active zone induces exocytosis.

What are the two types of synaptic transmission? How are they similar, how are they different?

There are electrical and chemical synapses. Electrical synapses are typically faster, lack a synaptic cleft, and require gap junctions called connexons to pass the action potential directly between connected plasma membranes. Chemical synapses are selectively permeable and plastic.

What limitations do chemical synapses have?

There is a brief delay in the pre-synaptic and post-synaptic responses, meaning it is slower than electrical synapses.

How are neuropeptides produced?

They are synthesized in the soma as a large polypeptide that is then cleaved into small molecules ranging from 3-36 amino acids. Microtubules -- by way of ATP hydrolysis for energy transport -- move them from the cell body, down the axon to the pre-synaptic terminus.

Why is an increase in presynaptic Ca++ both necessary and sufficient for synaptic transmission?

Because of it's strong driving force (high gradient) the calcium ions rush into the cell and cause a rapid depolarization, and also binds to vesicles to trigger neurotransmitter release.

What are the neuropeptide neurotransmitters?

Brain-gut, opioid, pituitary, and hypothalamic-releasing peptides.

How do electrical synapses function?

Depolarizatin of the pre-synaptic neuron causes sodium ions to flow through connexons and cause subsequent depolarization of the post-synaptic neuron.

What activates voltage gated Ca++ channels and what happens when they are activated?

Depolarization of the membrane to around -40 mV causes the channels to open and calcium ions rush into the presynaptic terminus and the vesicles release the neurotransmitters into the synaptic cleft

In the biogenic amine category, what are the three catecholamines?

Dopamine (DA), norepinephrine and epinephrine.

What are the biogenic amine neurotransmitters?

Dopamine, norepinephrine, and epinephrine; serotonin; and histamine.

What morphological features could allow you to distinguish an electrical from a chemical synapse?

Electrical synapses lack a synaptic cleft and have gap junctions. Conversely, chemical synapses have vesicles for neurotransmitter transport and a synaptic cleft.

Where are cholinergic cell bodies found in the CNS and where do they project?

Found in the brain and project to the rest of the cortex.

Where are cholinergic cell bodies found in the PNS and where do they project?

Found in the brain stem and project to the body.

What two main areas are dopaminergic cell bodies located in the brain, where do they project, and what functions is dopamine involved in?

Found in the substantia nigra and VTA and project to the striatum and functions in the reward driven learning, motivation, and emotion.

Where are glutamatergic cell bodies found in the brain, where do they project and what are glutamatergic neurons involved in?

Found mostly in the striatum and project all throughout the brain since it is the major excitatory neurotransmitter. "Most projection neurons are glutamatergic."

What is the general structure of a voltage gated Ca++ channel?

Four repeating transmembrane proteins with an alpha (inside) and beta (outside) subunit.

Where are GABAergic cell bodies found? What do they do?

GABAergic cells are found throughout the brain -- in the nucleus accumbens -- and is the main inhibitory neurotransmitter in the brain.

What are the substrates for GABA? What is the vesicular transporter for GABA and glycine?

GLUTAMATE DECARBOXYLASE degrades glutamate into GABA and it is then VIATT transporters package it into small synaptic vesicles.

What is one main substrate for glutamate?

GLUTAMINE released by glial cells and metabolized into glutamate by GLUTAMINASE. VGLUT transporters package glutamate into synaptic vesicles. EXCITATORY AMINO ACID TRANSPORTERS remove glutamate from the synaptic cleft. GLUTAMINE SYNTHETASE metabolized glutamate to glutamine.

How and where are synaptic vesicles generated?

Generated from the early endosome in the presynaptic terminus.

Which neurotransmitters are the main excitatory, inhibitory and modulatory?

Glutamate and aspartate are excitatory neurotransmitters. GABA and glycine are inhibitory neurotransmitters. Neuropeptides are typically neuromodulatory.

What are the four amino acid neurotransmitters?

Glutamate, aspartate, GABA, and glycine.

Where are glycinergic cell bodies found? What do they do?

Glycine is the major inhibitory neurotransmitter in the spinal cord and is found in the brain stem.

Describe how information flows through neurons.

Graded potentials received on the cell body/dendrites and are summated to generate outgoing action potentials down the axon as an electrical signal. The action potential is converted into a chemical signal in the form of neurotransmitters. Neurotransmitters stimulate the the target cell to produce an electrical response.

Why do neurons need to keep their intracellular Ca++ levels so low?

High levels of calcium in a cell can trigger apoptosis. Can also cause excitotoxicity and neurodegenerative disorders.

From what amino acid is imidazoleamine synthesized?

Histadine

In the category of biogenic amines, which one is in the imidazoleamine category?

Histamine

Where are vesicular neurotransmitter transporters found?

In the membranes of vesicles

How/why would increasing the frequency of action potentials lead to an increase in presynaptic Ca++ concentration and Ca++ microdomains? What effect would this have on neurotransmitter release?

Increasing action potentials would increase the amount of time that the plasma membrane is depolarized, meaning the voltage gated calcium channels would stay open and calcium levels would increase, thus neurotransmitter release would be amplified

Why do you think voltage gated K+ channels stay activated?

To reestablish and maintain the resting membrane potential after depolarization and action potentials

Small molecule neurotransmitters are packaged into what type of vesicles?

Small synaptic vesicles at the synapse

What and how much is a quantum of neurotransmitter?

3,000 to 9,000 neurotransmitter molecules

Neuropeptides are packaged into what type of vesicles?

Dense core granules or secretory vesicles in the endoplasmic reticulum

Historically, what are the defining characteristics of a neurotransmitter?

1. A chemical synthesized, packages, and released by the pre-synaptic neuron. 2. After release the chemical is either removed by degradation or reuptake. 3. The chemical produces a biological response on the post-synaptic target cell.

What are the ten common steps in synaptic transmission, and briefly, what does each step involve?

1. Neurotransmitters are synthesized and stored in vesicles. 2. An action potential travels down the axon to the presynaptic terminal. 3. Presynaptic terminal depolarizes and voltage-gated calcium channels open. 4. Calcium levels increase. 5. Vesicles fuse with presynaptic plasma membrane. 6. Nueortransmitters release into the synaptic cleft and diffuse. 7. Neurotransmitter binds to the receptor molecules on the postsynaptic membrane. 8. Postysynaptic channels open and depolarize the membrane. 9. Current causes excitatory or inhibitory postsynaptic potentials. 10. Neurotransmitter and vesicular membrane is recycled.

What are the steps to exocytosis?

1. Synaptobrevin binds to tSNARE proteins and the vesicle docks. 2. Calcium ions bind to synaptotagmin. 3. The SNARE complexes form to pull membranes together. 4. Calcium-bound synaptotagmin catalyzes membrane fusion.

Describe the process of calcium-stimulated exocytosis and subsequent neurotransmitter release.

1. The vesicle docks to the membrane by way of the V-snare and T-snare protein binding. 2. Synaptotagmin senses calcium ions flowing into the cell. 3. Calcium ions bind to synaptotagmin and induce membrane fusion. 4. Neurotransmitters are released into the synaptic cleft.

What is a synapse? What takes place at a synapse?

A structure where information is transferred from a pre-synaptic neuron to a target cell. Information is translated from electrical (AP) to chemical (Ca++) to chemical (NT) to electrical (EPSP).

What was the first neurotransmitter to be identified and in what system?

Acetylcholine in the muscular system

What are the four main types of small molecule neurotransmitters?

Acetylcholine, amino acids, biogenic amines, and purines.

What are the purine neurotransmitters?

Adenosine, ATP, and ADP.

Describe how synapses in the CNS and NMJ are similar and different.

CNS synapses are considered tripartite because they have a pre-synaptic neuron, an astrocyte for energy, and a post-synaptic target cell. NMJ typically have a larger extrasynaptic area than CNS.

How are the voltage gated Ca++ channels similar/different with respect to localization?

Calcium channels are dense in the presynaptic terminus at the active zone. Sodium channels are denser at the axon hilic and along the axon. Potassium channels are everywhere.

What is Ca2+?

Calcium is a metal, divalent ion that has a gradient of 10,000 to 1, outside to inside.

How are the voltage gated Ca++ channels similar/different with respect to mechanisms of activation?

Calcium is less sensitive requiring -40 mV

What are the substrates and enzyme involved in acetylcholine synthesis?

Choline acetyltransferase makes choline bind with Acetyl CoA to make ACh. Acetylcholine-esterase degrades ACh to choline and acetyl CoA.

What are cholinergic neurons involved in?

Cholinergic neurons are involved muscle movements at the neuromuscular junction.

What is a saltatory action potential?

Conduction down a myelinated axon. It is faster and more efficient.

What is a continuous action potential?

Conduction down an unmyelinated axon. It is slower and less efficient.

What two types of vesicle fusion/exocytosis are involved in NT release?

Kiss-and-run, a fast form of exocytosis in which the vesicle is recycled instead of becoming apart of the membrane. Full fusion when the vesicle membrane becomes apart of the plasma membrane.

How are voltage gated Ca++, Na+ and K+ channels similar, how are they different with respect to structure?

Like sodium, calcium has four domains of one polypeptide, with 6 repeating transmembrane proteins and a voltage sensor. Potassium has one domain with 6 different polypeptides.

Where are voltage gated Ca++ channels found/localized?

Localized at the active region (presynapse)

What is the main area where serotonergic cell bodies are located in the brain, where do they project, what functions is serotonin involved in?

Located in the dorsal raphe nucleus in the brain stem and project throughtout the brain and spinal cord to regulate depression, mood, and cognition.

What main areas are adrenergic (epinephrine) neuron cell bodies located?

Located in the lateral tegmental system and medulla and project to the hypothalamus and thalamus.

What main areas are noradrenergic (norepinephrine) neuron cell bodies located? What is the function for norepinephine within the brain?

Located in the pons, and project throughout the brain to regulate attention and arousal and sleep and wakefulness.

Where are the histaminergic neuron cell bodies localized, and what is histamine involved in (in the brain)?

Located in the posterior hypothalamus and involved in sleep, learning, and memory, specifically forgetting unimportant information.

What are and why are there Ca++ microdomains? How does this impact synaptic transmission?

Microdomains are sites in the cell with localized high levels of calcium, dependent upon the density and the number of action potentials generated by the cell. Thus, they create a sustained level of neurotransmitter release.

What are the three main types of neurotransmitters?

Small molecule and neuropeptides, which are conventional; and fatty acid derivatives, which are unconventional.

What is the vesicular transporter for glycine?

Small synaptic vesicles

What are the synaptic vesicle proteins?

Proton pumps, vesicular neurotransmitter transporter, synaptotagmin -- a calcium sensor -- and synaptobrevin -- V-snare protein.

In what ways could a presynaptic neuron regulate the amount of neurotransmitter it released?

Quick reuptake of calcium into mitochondria or the endoplasmic reticulum. Prolonged calcium levels. High or low levels of calcium. Frequency of action potentials to influence calcium release.

What do the vesicular neurotransmitter transporters depend on?

Rely on H+ gradient to transport neurotransmitters.

What are the advantages to chemical synaptic transmission?

Responses can be excitatory, inhibitory, or modulatory; they can also be fast and direct or slow and long-lasting ie they are plastic and their intensity can be changed.

What are vesicular neurotransmitter transporters?

Secondary active transporters that utilize the H+ gradient established by the H+ ATPase to move neurotransmitter molecules inside the synaptic vesicles.

In the category of biogenic amines, which neurotransmitter is a type of indoleamine?

Serotonin

What is the vesicular transporter for the biogenic amines?

Small synaptic vesicles