Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

202T1 > Chemicals in the brain > Flashcards

Chemicals in the brain Flashcards

1
Q

Briefly outline synaptic vesicle release and recycling

A

BUDDING: Vesicle forms from budding of endosome

DOCKING: Pool of vesicles above the active zone is anchored to the cytoskeleton by SYNAPSIN

PRIMING:
FUSION: Action potential to presynaptic terminal causes voltage-gated Ca2+ channels to open.

The influx of ca2+ into the cytoplasm activates CaMKII which phosphorylates synapsin. P-synapsin can no longer bind to cytoskeleton causing the vesicle to dock to active zone. SNARE causes this

**Vesicle membrane is quickly ENDOCYTOSED, new vesicles bud off and are refilled with NT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

How does exocytosis occur?

A

Vesicles dock at end of presynaptic cell (action of synapsin)

SNARE complexes form to pull membrane of vesicle and pre-synaptic membrane together

Entering Ca2+ binds to synaptotagmin

Ca2+ bound synaptotagmin catalyzes membrane fusion by binding to SNARES and the plasma membrane

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is priming and what is its role in exocytosis?

A

Docked vesicles are not ready for fusion and need to be primed before they are able to respond rapidly to increased intracelluar Ca2+. Priming involves partial assembly of SNARE complexes.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

CLINICAL APPLICATION

Chemical synaptic transmission can be impaired by cleavage of SNARE proteins by clostridial toxins. In what two contexs can this occur?

How does botox work?

A

SITES OF PROTEOLYSIS THAT BLOCKS NT RELEASE:
-Botulinum toxin (BoTX) -from clostridium botulinum decreases neuronmuscular transmission ACh.Botox prevents ACh release by binding to NMJ directly. The muscles lose all inpit and this leads to permananelty relaxes state. TREATMENT FOR MUSCLE SPASMS

-Tetanus toxin (TeTX)- from clostridium tetani at interneurons. It inhibits the release of glycine and GABA at inhibiting neurons –> disinhibition of cholinergic neurons –> permanent muscle contraction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

There are two types of membrane transporters. Describe them

A
  1. VESICULAR TRANSPORTERS POWERED BY H+ GRADIENT
    - ATPase H+ pump loads up vesicles with H+, this makes vesicles aicidic (pH5.5) compared to neutral cytoplasm (ph7.2)
  2. PLASMA MEMBRANE TRANSPORTERS POWERED BY ECG
    - [Na+] higher outside/[K+] higher inside
    - Glutamate cotransported with 2Na+
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is meant by the neural threesome?

A

TRIPARTITE SYNAPSE

Glia can release NT’s (like presynaptic terminals) and respond to NT’s (like postsynaptic terminals)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

State and briefly describe the 4 broad categories of neurotransmitters

A

Amino acids- synthesised locally in presynaptic terminals. FAST acting e.g. glutamate

Monoamine- stored in synaptic vesicles

Acetylcholine- released in response to local increase in Ca2+

Neuropeptides- synthesised in cell soma and transported to terminals stored in secretory granules. Released in response to global increase in Ca2+. SLOW (because they must migrate from soma to membrane)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Generally speaking, what are the physiological differences that occur at the presynaptic terminal when it stimulates at:

  1. a low frequency
  2. a high frequency
A
  1. Low frequency stimulation leads to
    - localised increase in [Ca2+]
    - neuropeptide in large dense-core vesicle release OR
    - small molecule NT in small clear-core vesicle release (preferentially released over NP)
  2. High frequency stimulation leads to:
    - more diffuse increase in [Ca2+]
    - release of both types of transporter
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Define and give an example of an excitatory and inhibitory NT

A

Excitatory NT- Slightly depolarises the post-synaptic cell membrane e.g. Glutamate
Inhibitory NT- Slightly hyperpolarises the post-synaptic cell membrane e.g. GABA (brain) or glycine(brainstem or spinal cord)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Consider diffuse modulatory systems

How does the serotonegic system work?

A

Function: mood, sleep, pain, emotion, appetite

Small set of neurons whichi arise from the brainstem

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the purpose of having multiple NT’s?

A

NT’s have modulating effects rather than information transmitting
(except InhibitNTs)- activate/inhibit circuits of neurons involved in brain functions
e.g. secretion of ACh –> activates cerebral cortex –> faciilitates learning BUT information learned and remembered is transmitted by neurons that secrete Glutamate and GABA

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Consider amino acid neurotransmitters

Describe how glutamate is synthesised, loaded, stored and recycled.

A

GLUTAMATE
Synthesis: at presynaptic terminal from glucose via krebs cycle or conversion of glutamine by glutaminase

Loaded and stored in vesicles by Vesicular glutamate transporters (VGLUTs)

Reuptake by Excitatory AA Transporters (EAATs) in the plasma membrane of presynaptic cells and surrounding glia

Glial cells convert glutamate backinto glutamine (which is then transported from glia to nerve terminal where it is converted back into glutamate.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Consider amino acid neurotransmitters

Describe how GABA is synthesised, loaded, stored and recycled.

A

y-AMINOBUTYNIC ACID
Synthesis: from glutamate in reaction catalysed gy Glutamic acid decarboxylase

Loaded and stored into vesicles by Vesicular GABA Transporter (GAT). Glycine uses the same transporter

Cleared from synapse by reuptake using transportes on glia and neurons inc. non-GABAergic neurons

Higher proportion of GABA is made, de novo, to refill vesicle, rather than recycling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

CLINICAL APPLICATION

Why is it important that amino acid NT release is regulated?

What happens in cerebral ischaemia and GHB(date rape drug)?

A

Too much glutamate/too little GABA –> hyperexcitabiility, epilepsy, excitotoxicity
Too much GABA- sedation/coma

Cerebral ischaemia leads to metabolic events that retain the ECG being abolished. This means there is a reversal of Na+/K+ gradient and so the membrane transporters release glutamate from cells by reversal operation
Excitotoxic cell death (Ca2+ –> enzymes –>digestion)

GHB
-A GABA metabolite that can be converted to GABA
Increased available GABA leads to loss of conscoiusness and coma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Consider monoamine neurotransmitters

Describe how Catecholamines are synthesised, loaded, stored and recycled. Give examples.

A

Dopamine, epinephrine, norepinephrine.
Dopamine synthesis occurs in 2 steps:
Tyrosine converted to DOPA by tyrosine hyrdroxylase
DOPA is converted to DA by DOPA decarboxylase

Norepinephrine is synthesised from DA by DBH
Epinephrine is synthesised from NE by PNMT

They are stored and loaded into vesicles by VMATs

Released by Ca2+ dependent exocytosis. Ca2+ binds and activates receptor, signal terminated by reuptake into the axon terminal by Dopamine transporters (DATs) and Norepinephrine transporters (NETs) powered by ECG.

In the cytoplasm , the catecholamines are either reloaded back into vesicles , enzymatically degraded by Monoamine oxidases (MAO’s) or inactivated by Catechol-O-methyl-transferase (COMT)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Consider monoamine neurotransmitters

Describe how Indolamines are synthesised, loaded, stored and recycled. Give an examine

A

SEROTONIC (5HT)
Synthesis in two steps:
Tryptophan to 5-HTP by tryptophan hydroxylase. 5-HTP to 5-HT by 5-HTP decarboxylase

Stored in vesicles

Signal terminated by reuptake by Serotonin transporters (SERTs) on presynaptic membrane

17
Q

Give an example of a prescription and recreational drug that is a catecholamine. Decribe their mechanisms of action

A

Amphetamines- reverses transporter so pumps out NT and blocks reuptake

Cocaine (&Ritalin)- blocks Dopamine reuptake into terminals –> increased DA in synaptic cleft –> extended action on postysynaptic neuron

18
Q

Give an example of a prescription and recreational drug that is an Indolamine. Describe their mechanisms of action

A

Fenfluramine- stimulates the releases of serotinin nd inhibits its reuptake. Appetite suppression in obesity

MDMA (Ecstasy)- causes NE and Serotonin transporters to run backwards, releasing NT into synapse.

19
Q

Consider acetylcholine as a neurotransmitter

Describe how it is synthesised, loaded, stored and recycled.

A

Choline acteyltransferase (ChAT, CAT) converts choline+ Acteyl CoA into ACh

Packages into vesicular ACh transporter (VAChT)

Rapidly degraded in synaptic cleft by acteylcholinesterase (AChE)

Choline is transported back into presynaptic terminal and converted to ACh. The RDS here is the concentration of choline. AChE is made by the cholinergic neuron, secreted into cleft and associated with the axonal membrane

20
Q

What is the mechanism of action of Neostigmine?

A

Inhibits Acetyl cholinestrase thus blocking the breakdown of ACh in the cleft, prolonging its actions in the synaptic cleft

Used as a treatment of myaesthenia gravis)

21
Q

Consider neuropeptides as a neurotransmitter

Describe how they are synthesised, loaded, and stored

A

SLOW TRANSMISSION
Vary in methods of synthesis and release. Comprised of short chain polypeptide (3-36 AAs)

Small clear-core vesicles:
Synthesis of enzymes in cell body –> slow axonal transport of enzymes –> synthesis and packaging of NT –> release and diffusion of NT –> transport of precursor into terminal

Peptide neurotransmitter (Large dense):
Synthesis of NT precursor and enzyme in cell body -->transport of enzymes and peptide precursor down microtubule tracks--> enzymes modify precursor to produce peptide NT --> NT diffuses away and degraded by proteolytic enzymes (in response to a global increase in Ca2+ by sustained or repeated depolarization)
THE BIND TO AND ACTIVATE RECEPTOR
22
Q

What happens to neuropeptides after release?

A

Vesicle membrane is recycled but not refilled

23
Q

Brefly describe two other types of neurotransmitters

A

Endocannibinoids
- small lipids which mostly cause decreased GABA release at certain inhibitory terminals

Soluble gases
- e.g. NO and CO
NO synthesized in post-synaptic neuron by NO synthase(activated by Ca2+ binding and calmodulin) –> Gas is not stored, rapidly diffuses from site of synthesis to pre-synaptic cell –> Activates guanylyl cyclase which activates cGMP as a 2nd messenger –> within seconds of NO production it is converted to biologically inactive signal SWITCHES OFF SIGNAL

Potentially useful for coordination activity of multiple cells in small regions

NO is RETROGRADE TRANSMITTER

202T1 (19 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions