neuroscience - chapter 8 Flashcards

1
Q

Define neurotransmitter systems. (simple definition)

A

Neurotransmitter systems refer to the networks of neurons and chemical messengers (neurotransmitters) that work together to transmit signals across the brain and nervous system. Each system typically involves a specific neurotransmitter (like dopamine, serotonin, or acetylcholine) and a set of receptors, enzymes, and pathways that influence various mental and physical functions, such as mood, movement, and cognition.

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2
Q

What are the three types of neurotransmitters?

A

Amino acids, amines and peptides.

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3
Q

What does this chapter focus on?

A

-Criteria and methods used to identify NTs
-NT life cycle, from synthesis to degradation (for specific NTs & learn where drugs act)

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4
Q

What are the four criteria a molecule must meet to be considered a neurotransmitter?

A
  1. Synthesis and localization (the molecule must be synthesized and stored in pre-synaptic neurons)
  2. Release (the molecule must be released by the presynaptic terminal upon stimulation)
  3. Response mimicry (when experimentally applied, the molecule must produce a response that mimics the response of a post-synaptic cell to the NT release)
  4. Inactivation/degradation (the molecule must be actively removed from the synaptic cleft)
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5
Q
  1. SYNTHESIS AND LOCALIZATION
    Enzymes for making the NT should be present for which neurotransmitters?
A

Amino acids and amines.
NOT peptides.

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6
Q

Name the two different methods for localization.

A
  1. Immunohistochemistry
  2. In situ hybridization
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7
Q

Describe the process of immunohistochemistry (if applied to a tissue).

A
  • Used to anatomically localize an NT or the enzyme that makes it
  • Create “tagged” antibodies for the NT or enzyme

process:
(a) The molecule of interest (a neurotransmitter candidate) is injected into an animal, causing an immune response and the generation of antibodies. (b) Blood is withdrawn from the animal, and the antibodies are isolated from the serum. (c) The antibodies are tagged with a visible marker and applied to sections of brain tissue. The antibodies label only those cells that contain the neurotransmitter candidate. (d) A close-up of the complex that includes the neurotransmitter candidates, an antibody, and its visible marker.

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8
Q

What must the neurotransmitter demonstrate to satisfy criterion 1?

A

To satisfy criterion 1, you must demonstrate that the candidate neurotransmitter AND the enzyme that synthesizes are contained in the same neuron, or better still, the same axon terminal.

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9
Q

Describe the process of in situ hybridization (if applied to a tissue).

A
  • Locates the mRNA for peptide NTs and their synthesizing enzymes
  • A radioactively labelled strand of complimentary mRNA
  • Only cells with the target mRNA become radioactive

In situ hybridization. Strands of mRNA consist of nucleotides arranged in a specific sequence. Each nucleotide will stick to one other complementary nucleotide.
In the method of in situ hybridization, a synthetic probe is constructed containing a sequence of complementary nucleotides that will allow it to stick to the mRNA. If the probe is labeled, the location of cells containing the mRNA will be revealed.

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10
Q

What must the neurotransmitter demonstrate to satisfy criterion 1?

A

Same thing. To satisfy criterion 1, you must demonstrate that the candidate neurotransmitter AND the enzyme that synthesizes are contained in the same neuron, or better still, the same axon terminal.

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11
Q
  1. RELEASE
    In order for the neurotransmitters to be released, what needs to happen?
A

Stimulation!

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12
Q

Describe the release process in the PNS.

A

*a specific set of cells or axons can be stimulated while taking samples of the fluids bathing their synaptic targets (Loewi’s frog heart study?).
*The biological activity cause by the sample can then be tested to see if it mimics the effect of the intact synapses.
*sample can then be chemically analyzed to reveal the structure of the active molecule.

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13
Q

Describe the release process in the CNS.

A

*Until recently, it was impossible to stimulate
(electrically) a single population of synapses
containing only a single neurotransmitter, so
many synapses in a region of the brain and Loading…
researchers had to be content with stimulating
collecting and measuring all the chemicals that were released (in brain slices in “in vitro” preparations).
*With the advent of “optogenetics”, it is now possible to activate just one specific type of synapse at a time. Genetic methods are used to induce one particular type of neuron to express light-sensitive ion channels, and then those neurons can be stimulated with brief flashes of light. Any transmitters released are likely to have come from the optogenetically selected type of synapse.

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14
Q

Define optogenetic stimulation.

A

Optogenetic stimulation is the use of light to activate specific cells, usually neurons, that have been genetically modified to respond to light. This method allows precise control of cell activity to study how these cells affect behaviour, brain function, or other biological processes. (target specific neurons)

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15
Q
  1. RESPONSE MIMICRY BY IONTOPHORESIS
    Describe the process.
A

Applying the molecule (to a “postsynaptic” neuron) results in a synaptic response that mimics stimulation of the axon

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16
Q

Define micro iontophoresis.

A

This method enables a researcher to apply drugs or neurotransmitter candidates in very small amounts to the surface of neurons. The responses generated by the drug can be compared to those generated by synaptic stimulation.

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17
Q

Is this criteria alone proof of the candidate being a neurotransmitter?

A

Notice that molecules other than the NT can also interact with receptors, so this criterion by itself is no “proof” of the candidate molecule being a NT.

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18
Q
  1. INACTIVATION
    Describe the process.
A

Specific mechanisms remove the molecule (viewed previously).

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19
Q

Define neurotransmitter synthesis.

A

Neurotransmitter synthesis is the process by which neurons produce neurotransmitters, the chemical messengers used to send signals across the nervous system.

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20
Q

Which type of neurotransmitter is made where?

A

-peptide NTs made in soma
-amino acid and amine NT made in the axon terminal

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21
Q

Describe the synthesis of peptide neurotransmitters.

A

(a) Peptides:
1. A precursor peptide is synthesized in the rough endoplasmic reticulum. 2. The precursor peptide is split in the Golgi apparatus to yield the active neurotransmitter.
3. Secretory vesicles containing the peptide bud off from the Golgi apparatus.
4. The secretory granules are transported down the axon to the terminal where the peptide is stored.

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22
Q

Define Dale’s principle.

A

The convention established by Dale classifies neurons into mutually exclusive groups by neurotransmitter (cholinergic, glutamatergic, GABAergic, and so on).The idea that a neuron has only one neurotransmitter is often called Dale’s principle. (one neuron will only release one neurotransmitter = not true)

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23
Q

Why is Dale’s principle wrong?

A

Many peptide-containing neurons violate Dale’s principle because these cells usually release more than one neurotransmitter: an amino acid or amine and a peptide. When two or more transmitters are released from one nerve terminal, they are called co-transmitters .

24
Q

Let’s go over the NT synthesis.
1. where are peptides + a.a.&amines synthesized?
2. where are peptides + a.a.&amines transported?
3. name of vesicles of peptides + a.a.&amines?

A
  1. peptides=soma (rough ER and Golgi apparatus)
    a.a.&amines=axonal terminal
  2. peptides=down axon hillock
    a.a.&amines=not transported
    3.peptides=secretory granules (from Golgi apparatus)
    a.a.&amines=synaptic vessicles
25
Q

Which player regulates NT synthesis?

A

enzymes!

26
Q

Describe the process of how enzymes regulate NT synthesis (talk about precursors, enzymes, products, and transmitters.)

A

Enzymes regulate NT Synthesis
* A precursor (A) is modified by an enzyme
* The product (B) is modified by another enzyme
* The product (C) is modified by another enzyme
* The Transmitter is produced

27
Q

Talk about how this is an example of the NT dopamine.

A

modified by another enzyme
Here’s an example using the synthesis of dopamine, a neurotransmitter in the catecholamine family. This pathway involves multiple steps with different enzymes and intermediates:
Precursor (A): Tyrosine
¿ Tyrosine is an amino acid obtained from the diet and serves as the initial precursor.
Enzyme 1: Tyrosine hydroxylase (TH)
Tyrosine hydroxylase catalyzes the conversion of tyrosine to the next intermediate.
Product (B): L-DOPA (L-3,4-dihydroxyphenylalanine)
he Transmitter is produced
This is an intermediate product in the dopamine synthesis pathway.
Enzyme 2: DOPA decarboxylase
This enzyme converts L-DOPA into dopamine, the final neurotransmitter.
Product (C) and Transmitter: Dopamine
Dopamine is the final product in this specific pathway and acts as the neurotransmitter.

28
Q

What are the two ways to control synthesis?

A

The rate-limiting step and feedback inhibition.

29
Q

Describe the rate-limiting step.

A

Part that can slow down the process.

Example of rate-limiting step:
If C is in short supply, then it becomes a rate-limiting step
If C is always available, but there is little of the enzyme for converting C to NT, then the enzyme is the rate-limiting step
Controlling this step allows control of the overall synthesis of NT

30
Q

Describe feedback inhibition.

A

Goal: to prevent the synthesis of too much NT

Mechanism: high levels of NT slow down NT synthesis.

How does it work?
-Autoreceptors (presynaptic terminals) bind to NT
-Activate a second messenger
-Inhibits the rate-limiting step

31
Q

Let’s now look at specific NTs.

A

AMINES
-Acetylcholine
-Catecholamines (Dopamine, Norepinephrine, Epinephrine Serotonin)

AMINO ACID TRANSMITTERS
-Glutamate (excitatory)
-GABA
-Glycine (inhibitory)

NEUROPEPTIDES
-Substance P
-Opioid peptides

NITIC OXIDE (N.O.) (not a classical/standard neurotransmitter)

32
Q

ACETYLCHOLINE
what is this NT made of? and what does it release?

A

acetyl+choline=Ach+CoA

33
Q

Degrading Ach after release.

A

Ach broken up by enzyme. broken into acetic acid+choline

34
Q

How is choline recycled?

A

look slide 26

35
Q
  1. CATECHOLAMINES (amines)
    What do the catecholamines dopamine, norepinephrine and epinephrine have in common?
A

They all have the catechol group. It is a benzenediol comprising of a benzene core carrying two hydroxy groups.

36
Q

Dopamine synthesis is done by which 2 steps?

A

Hydroxylation and decarboxylation

37
Q

Precursors for epinephrine synthesis.

A

tyrosine to L-Dopa to dopamine to norepinephrine to epinephrine

38
Q

L-dope is used to treat what disease? And why?

A

Parkinson’s disease because it increases DA available for release in surviving DA neurons.

39
Q

Explain how to terminate the action of DA.

A

broken down by two enzymes:
COMT (Catechol-O-methyltransferase) MAO (monoamine oxidases) + SLIDE 29

40
Q

What is schizophrenia treated with?

A

DA antagonists.

41
Q

Describe norepinephrine synthesis.

A

-Dopamine is converted to Norepinephrine.
- Enzyme is Dopamine-β- hydroxylase.
-Action is terminated in the
same way as DA: re-uptake and degradation by MAO and COMT.

42
Q

Describe epinephrine synthesis.

A

Norepinephrine is converted to epinephrine (EPI).
* Enzyme is PNMT.
* Action is terminated in the same way as DA: re-uptake
and degradation by MAO and COMT.
* EPI is used in EpiPen (the brand name of an auto-
injectable device that delivers the drug epinephrine) to treat allergic reactions
* Also activates sympathetic NS (speeds heart rate etc.)

43
Q
  1. SEROTONIN
    What are the two steps of synthesis of serotonin?
A

Two steps: hydroxylation and decarboxylation (just like DA)

44
Q

What is the precursor of serotonin?

A

Tryptophan.

45
Q

How to inactivate serotonin?

A

Some drugs block re-uptake (antidepressant fluoxetine = “Prozac”)
Some drugs are MAO inhibitors (antidepressant iproniazid = “Marsilid”) + HONESTLY GO REVIEW SLIDE 33

46
Q

What are the three amino acid trasmitters?

A

Glutamate, glycine and GABA

47
Q

Which ones are excitatory and which are inhibitory?

A

excitatory: glutamate
inhibitory: glycine and GABA

48
Q

Which ones are used for building proteins?

A

Glutamate and GABA.

49
Q

Talk about glutamate.

A

Amino acid transmitters: Glutamate Synthesis is not required (it’s already present in all cells)
Glutamate is the most common excitatory NT
In excessive quantities, it can kill cells by overexciting them (“excitotoxicity”)
Released during ischemia (stroke) Action is terminated by re-uptake

50
Q

Talk about glycine.

A

An Inhibitory NT
most prominent in spinal cord, brainstem and retina
Strychnine (used primarily as a pesticide, particularly to kill rats) blocks glycine receptors
Blocks inhibition, which leads to convulsions

51
Q

What happens if you block glycine receptor?

A

glycine can’t inhibit post-synaptic cell , increase firing-rate, not matter how much glycine released the post-synaptic cell cannot receive that glycine and produce IPSP’s for it

52
Q

Talk about GABA.

A

The most common inhibitory NT in the brain
Glutamate is converted into GABA
Via the enzyme Glutamic acid decarboxylase (GAD): relevant to epilepsy!

53
Q
  1. NEUROPEPTIDES
A

Made in the soma
* Transported to terminal by secretory granules

54
Q

Talk about opioid peptides (endorphins).

A

Enkephalins (met- and leu-enkephalin) are cut from a longer protein (proenkephalin)

55
Q

Name two exogenous opioids and what they bind to.

A

Morphine and Heroin are exogenous opioids that bind to opioid receptors.

56
Q
  1. NITRIC OXIDE (NO)
A

-a gaseous NT
-produced in neurons and in blood vessels
In blood vessels, it causes smooth muscle around vessels walls
to relax, dilating the vessels (Viagra)
In nervous system, NO can diffuse from one neuron to
another
Serves as a “retrograde messenger” (from postsynaptic to presynaptic neurons), challenging the idea that synaptic communication is a one-way street

57
Q
A