_Botox and Tetanus_ Botox and Tetanus - Prevent ... release Botulinium and tetanus toxin - from bacteria Clostridium Botulinum and Tetani respectively Botox acts directly at the ... ... - the muscles lose all input and so become permanently ... (treatment of muscle ...) Tetanus toxin inhibits the release of .. and .. at inhibitory neurons, resulting in dis-inhibition of ... neurons, which causes permanent muscle ...

Botox and Tetanus - Prevent transmitter release Botulinium and tetanus toxin - from bacteria Clostridium Botulinum and Tetani respectively Botox acts directly at the NT junction - the muscles lose all input and so become permanently relaxed (treatment of muscle spasms) Tetanus toxin inhibits the release of Glycine and GABA at inhibitory neurons, resulting in dis-inhibition of cholinergic neurons, which causes permanent muscle contraction

_Glia_ Majority of cells of brain \>...% Can release NT themselves and respond to them Involve in many diseases - brain cancer, HIV, dementia Very important - crucial for correct functioning of ... but not enough known about them

Majority of cells of brain \>80% Can release NT themselves and respond to them Involve in many diseases - brain cancer, HIV, dementia Very important - crucial for correct functioning of synapses but not enough known about them

_Categories of Neurotransmitters:_ Amino acids , Monoamines , Acetylcholine Synthesized locally in ... terminal Stored in ... vesicles Released in response to local increase in ...+ Neuropeptides Synthesized in the cell ... and transported to the terminal Stored in ... granules Released in response to global increase in ...+

Amino acids , Monoamines , Acetylcholine Synthesized locally in presynaptic terminal Stored in synaptic vesicles Released in response to local increase in Ca2+ Neuropeptides Synthesized in the cell soma and transported to the terminal Stored in secretory granules Released in response to global increase in Ca2+

_Categories of Neurotransmitters:_ Amino acids , ... , ... Synthesized locally in presynaptic terminal Stored in synaptic vesicles Released in response to ... increase in Ca2+ ...peptides Synthesized in the cell soma and transported to the terminal Stored in secretory ... Released in response to ... increase in Ca2+

Amino acids , Monoamines , Acetylcholine Synthesized locally in presynaptic terminal Stored in synaptic vesicles Released in response to local increase in Ca2+ Neuropeptides Synthesized in the cell soma and transported to the terminal Stored in secretory granules Released in response to global increase in Ca2+

_Amino acid NT - fast_ ...: slightly depolarises the postsynaptic cell's membrane Glutamate (Glu) - CNS ...: slightly hyperpolarises the postsynaptic cell's membrane GABA - brain Glycine (Gly) - spinal cord and brain stem

Excitatory: slightly depolarises the postsynaptic cell's membrane Glutamate (Glu) - CNS Inhibitory: slightly hyperpolarises the postsynaptic cell's membrane GABA - brain Glycine (Gly) spinal cord and brain stem

_Amino acid NT - fast_ Excitatory: slightly depolarises the postsynaptic cell's membrane ... (...) - CNS Inhibitory: slightly hyperpolarises the postsynaptic cell's membrane ... - brain ... (...) - spinal cord and brain stem

Excitatory: slightly depolarises the postsynaptic cell's membrane Glutamate (Glu) - CNS Inhibitory: slightly hyperpolarises the postsynaptic cell's membrane GABA - brain Glycine (Gly) spinal cord and brain stem

Chemicals in the Brain Flashcards by Chrissy Taaffe

Synaptic Vesicle release and recycling

Pool of vesicles above the active zone is anchored to the cytoskeleton by …
AP to presynaptic terminal, voltage gated Ca2+ channels open, Ca2+ flows into cytoplasm
Ca2+ activates Calcium calmodulin activated kinase II (CaMKII) which phosphorylates …. P-… can no longer bind to the cytoskeleton, vesicles dock to the active zone
…* complex at active zone docks vesicles to the plasma membrane

Pool of vesicles above the active zone is anchored to the cytoskeleton by synapsin
AP to presynaptic terminal, voltage gated Ca2+ channels open, Ca2+ flows into cytoplasm
Ca2+ activates Calcium calmodulin activated kinase II (CaMKII) which phosphorylates synapsin. P-synapsin can no longer bind to the cytoskeleton, vesicles dock to the active zone
SNARE* complex at active zone docks vesicles to the plasma membrane

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Synaptic Vesicle release and recycling

Pool of vesicles above the active zone is anchored to the cytoskeleton by synapsin
AP to presynaptic terminal, voltage gated …+ channels open, …+ flows into cytoplasm
…+ activates … … activated kinase II (CaMKII) which phosphorylates synapsin. P-synapsin can no longer bind to the cytoskeleton, vesicles dock to the active zone
SNARE* complex at active zone docks vesicles to the plasma membrane

Pool of vesicles above the active zone is anchored to the cytoskeleton by synapsin
AP to presynaptic terminal, voltage gated Ca2+ channels open, Ca2+ flows into cytoplasm
Ca2+ activates Calcium calmodulin activated kinase II (CaMKII) which phosphorylates synapsin. P-synapsin can no longer bind to the cytoskeleton, vesicles dock to the active zone
SNARE* complex at active zone docks vesicles to the plasma membrane

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Mechanisms of exocytosis during NT release

… and … on pre-synaptic vesicle
Syntaxin and SNAP-25 on post-synaptic vesicle
AP arrives - calcium channel open, higher locally in area - … complex forms to pull membranes together
Entering calcium ions binds to synaptotagmin
Calcium bound synaptotagmin catalyses membrane fusion by binding to … and the plasma membrane

Synaptobrevin and Synaptotagmin on pre-synaptic vesicle
Syntaxin and SNAP-25 on post-synaptic vesicle
AP arrives - calcium channel open, higher locally in area - SNARE complex forms to pull membranes together
Entering calcium ions binds to synaptotagmin
Calcium bound synaptotagmin catalyses membrane fusion by binding to SNAREs and the plasma membrane

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Mechanisms of exocytosis during NT release

Synaptobrevin and Synaptotagmin on pre-synaptic vesicle
… and SNAP-… on post-synaptic vesicle
AP arrives - calcium channel open, higher locally in area - SNARE complex forms to pull membranes together
Entering … ions binds to synaptotagmin
… bound synaptotagmin catalyses membrane fusion by binding to SNAREs and the plasma membrane

Synaptobrevin and Synaptotagmin on pre-synaptic vesicle
Syntaxin and SNAP-25 on post-synaptic vesicle
AP arrives - calcium channel open, higher locally in area - SNARE complex forms to pull membranes together
Entering calcium ions binds to synaptotagmin
Calcium bound synaptotagmin catalyses membrane fusion by binding to SNAREs and the plasma membrane

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Synaptic vesicle release and recycling

After the exocytosis, vesicle membrane is rapidly recovered via …, new vesicles bud off and are refilled with transmitter
whole process takes … …

After the exocytosis, vesicle membrane is rapidly recovered via endocytosis, new vesicles bud off and are refilled with transmitter
whole process = 1 minute

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Cleavage of SNARE proteins by clostridial toxins

SNARE proteins important for NT to function
- … toxin - affects transmission of Ach
- … toxin - acts on interneurons as spinal cord (inhibitory) affect release of GABA and Gly - 2 inhibitory NT
Little boxes - sites of SNARE proteins
BoTX and TeTX can act here

SNARE proteins important for NT to function
- Botulinum toxin - affects transmission of Ach
- Tetanus toxin - acts on interneurons as spinal cord (inhibitory) affect release of GABA and Gly - 2 inhibitory NT
Little boxes - sites of SNARE proteins
BoTX and TeTX can act here

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Cleavage of SNARE proteins by clostridial toxins

SNARE proteins important for NT to function
- Botulinum toxin - affects transmission of …
- … toxin - acts on interneurons as spinal cord (inhibitory) affect release of … and … - 2 inhibitory NT
Little boxes - sites of SNARE proteins
BoTX and TeTX can act here

SNARE proteins important for NT to function
- Botulinum toxin - affects transmission of Ach
- Tetanus toxin - acts on interneurons as spinal cord (inhibitory) affect release of GABA and Gly - 2 inhibitory NT
Little boxes - sites of SNARE proteins
BoTX and TeTX can act here

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Botox and Tetanus - Prevent … release

Botox and Tetanus - Prevent transmitter release

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Botox and Tetanus

Botox and Tetanus - Prevent … release
Botulinium and tetanus toxin - from bacteria Clostridium Botulinum and Tetani respectively
Botox acts directly at the … … - the muscles lose all input and so become permanently … (treatment of muscle …)
Tetanus toxin inhibits the release of .. and .. at inhibitory neurons, resulting in dis-inhibition of … neurons, which causes permanent muscle …

Botox and Tetanus - Prevent transmitter release
Botulinium and tetanus toxin - from bacteria Clostridium Botulinum and Tetani respectively
Botox acts directly at the NT junction - the muscles lose all input and so become permanently relaxed (treatment of muscle spasms)
Tetanus toxin inhibits the release of Glycine and GABA at inhibitory neurons, resulting in dis-inhibition of cholinergic neurons, which causes permanent muscle contraction

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Diseases that affect the presynaptic terminal

Congenital … syndromes - impaired vesicle recycling
Another type of … - LEMS - attacks presynaptic Ca2+ channels
… disorders - impair transsynaptic signalling
…toxin - triggers vesicle fusion (black widow spider poison)
Botulinum and tetanus toxins - … proteins affected involved in vesicle fusion

Congenital myasthenic syndromes - impaired vesicle recycling
Another type of myasthenia - LEMS - attacks presynaptic Ca2+ channels
Cognitive disorders - impair transsynaptic signalling
Latrotoxin - triggers vesicle fusion (black widow spider poison)
Botulinum and tetanus toxins - SNARE proteins affected involved in vesicle fusion

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Membrane transporters - amino acids, amines and Ach

Bringing back NT from synaptic cleft to presynaptic neuron - reload into vesicles
Vesicular transporters powered by … gradient:
- … proton pump loads up vesicles with H+ making vesicles acidic (pH 5.5) compared to neutral pH of cytoplasm (pH7.2) e.g. 1 glutamate traded for 1 H+ (counter-transport mechanism)
Plasma membrane transporters powered by … gradient
- Na+ higher outside, K+ higher inside
- … co-transported with 2 Na+

Bringing back NT from synaptic cleft to presynaptic neuron - reload into vesicles
Vesicular transporters powered by proton gradient:
- ATPase proton pump loads up vesicles with H+ making vesicles acidic (pH 5.5) compared to neutral pH of cytoplasm (pH7.2) e.g. 1 glutamate traded for 1 H+ (counter-transport mechanism)
Plasma membrane transporters powered by electrochemical gradient
- Na+ higher outside, K+ higher inside
- Glutamate co-transported with 2 Na+

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Membrane transporters - amino acids, amines and Ach

Bringing back NT from … cleft to … neuron - reload into vesicles
Vesicular transporters powered by proton gradient:
- ATPase proton pump loads up vesicles with H+ making vesicles acidic (pH 5.5) compared to neutral pH of cytoplasm (pH7.2) e.g. 1 glutamate traded for 1 H+ (counter-transport mechanism)
Plasma membrane transporters powered by electrochemical gradient
- …+ higher outside, …+ higher inside
- Glutamate co-transported with … Na+

Bringing back NT from synaptic cleft to presynaptic neuron - reload into vesicles
Vesicular transporters powered by proton gradient:
- ATPase proton pump loads up vesicles with H+ making vesicles acidic (pH 5.5) compared to neutral pH of cytoplasm (pH7.2) e.g. 1 glutamate traded for 1 H+ (counter-transport mechanism)
Plasma membrane transporters powered by electrochemical gradient
- Na+ higher outside, K+ higher inside
- Glutamate co-transported with 2 Na+

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Glia

Majority of cells of brain >…%
Can release NT themselves and respond to them
Involve in many diseases - brain cancer, HIV, dementia
Very important - crucial for correct functioning of … but not enough known about them

Majority of cells of brain >80%
Can release NT themselves and respond to them
Involve in many diseases - brain cancer, HIV, dementia
Very important - crucial for correct functioning of synapses but not enough known about them

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Categories of Neurotransmitters:

Amino acids , Monoamines , Acetylcholine
- Synthesized locally in … terminal
- Stored in … vesicles
- Released in response to local increase in …+
Neuropeptides
- Synthesized in the cell … and transported to the terminal
- Stored in … granules
- Released in response to global increase in …+

Amino acids , Monoamines , Acetylcholine
- Synthesized locally in presynaptic terminal
- Stored in synaptic vesicles
- Released in response to local increase in Ca2+
Neuropeptides
- Synthesized in the cell soma and transported to the terminal
- Stored in secretory granules
- Released in response to global increase in Ca2+

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Categories of Neurotransmitters:

Amino acids , … , …
- Synthesized locally in presynaptic terminal
- Stored in synaptic vesicles
- Released in response to … increase in Ca2+
…peptides
- Synthesized in the cell soma and transported to the terminal
- Stored in secretory …
- Released in response to … increase in Ca2+

Amino acids , Monoamines , Acetylcholine
- Synthesized locally in presynaptic terminal
- Stored in synaptic vesicles
- Released in response to local increase in Ca2+
Neuropeptides
- Synthesized in the cell soma and transported to the terminal
- Stored in secretory granules
- Released in response to global increase in Ca2+

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Neurotransmitters in the CNS

Fast e.g. … …
Slow e.g. …

Fast e.g. amino acids (GLUTAMATE/GABA)
Slow e.g. neuropeptides (Oxytocin,noradrenaline)

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Amino acid NT - fast

…:
- slightly depolarises the postsynaptic cell’s membrane
- Glutamate (Glu) - CNS
…:
- slightly hyperpolarises the postsynaptic cell’s membrane
- GABA - brain
- Glycine (Gly) - spinal cord and brain stem

Excitatory:
- slightly depolarises the postsynaptic cell’s membrane
- Glutamate (Glu) - CNS
Inhibitory:
- slightly hyperpolarises the postsynaptic cell’s membrane
- GABA - brain
- Glycine (Gly) spinal cord and brain stem

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… neurotransmitters - slightly hyperpolarises the postsynaptic cell’s membrane

Inhibitory neurotransmitters - slightly hyperpolarises the postsynaptic cell’s membrane

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Amino acid NT - fast

Excitatory:
- slightly depolarises the postsynaptic cell’s membrane
- … (…) - CNS
Inhibitory:
- slightly hyperpolarises the postsynaptic cell’s membrane
- … - brain
- … (…) - spinal cord and brain stem

Excitatory:
- slightly depolarises the postsynaptic cell’s membrane
- Glutamate (Glu) - CNS
Inhibitory:
- slightly hyperpolarises the postsynaptic cell’s membrane
- GABA - brain
- Glycine (Gly) spinal cord and brain stem

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… neurotransmitters - slightly depolarises the postsynaptic cell’s membrane

Excitatory neurotransmitters - slightly depolarises the postsynaptic cell’s membrane

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GABA (brain) and glycline (spinal cord and brain stem) are both what type of neurotransmitter?

Inhibitory - slightly hyperpolarises the postsynaptic cell’s membrane

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Glutamate (Glu) - CNS is what type of neurotransmitter?

Excitatory - slightly depolarises the postsynaptic cell’s membrane

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Diffuse modulatory systems e.g. the Serotonergic system

Function in: m…, sleep, p…, emotion, a..
Common principles : core
- small set of neurons. most arise from … …
- 1 -> 100,000 (Each neuron can affect many others, because each one has an axon that may contact more than 100,000 postsynaptic neurons spread widely across the brain.)

Function in: mood, sleep, pain, emotion, appetite
Common principles : core
- small set of neurons. most arise from brain stem
- 1 -> 100,000 (Each neuron can affect many others, because each one has an axon that may contact more than 100,000 postsynaptic neurons spread widely across the brain.)

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Diffuse modulatory systems e.g. the Serotonergic system

Function in: mood, …, pain, …, appetite
Common principles : core
- small set of neurons. most arise from … ….
- 1 -> 100,000 (Each neuron can affect many others, because each one has an axon that may contact more than 100,000 postsynaptic neurons spread widely across the brain.)

Study These Flashcards

Function in: mood, sleep, pain, emotion, appetite
Common principles : core
- small set of neurons. most arise from brain stem
- 1 -> 100,000 (Each neuron can affect many others, because each one has an axon that may contact more than 100,000 postsynaptic neurons spread widely across the brain.)

_Why have more NT's?_

* 6 different layers of neuro-cortex - Different inputs and outputs * E.g top layers - feedback connections with other parts of cortex * 3 and 4 - mainly thalamus * 5 and 6 - cortical structure * Complexity in terms of wiring and inputs and outputs

_Glutamate - excitatory_ * Synthesized in presynaptic terminal from 2 sources * From glucose via the ... cycle * From glutamine converted by glutaminase into glutamate * Loaded and ... in vesicles by vesicular glutamate ... (VGLUTs) * ... by excitatory amino acid transporters (EAATs) in the plasma membrane of presynaptic cell and surrounding glia * Glial cells convert Glu to glutamine and this is transported from the glia back to nerve terminals where it is converted back into glutamate

* Synthesized in presynaptic terminal from 2 sources * From glucose via the **Krebs cycle** * From glutamine converted by glutaminase into glutamate * Loaded and **stored** in vesicles by vesicular glutamate **transporters** (VGLUTs) * **Reuptake** by excitatory amino acid transporters (EAATs) in the plasma membrane of presynaptic cell and surrounding glia * Glial cells convert Glu to glutamine and this is transported from the glia back to nerve terminals where it is converted back into glutamate

_GABA (y-aminobutyric acid) - inhibitory_ * Synthesized from ... (...) in a reaction catalyzed by glutamic acid decarboxylase (GAD) * Loaded and stored into vesicles by a vesicular GABA transporter, GAT (Gly uses the same transporter) * Cleared from synapse by ... using transporters on glia and neurons including non-GABAergic neurons * Higher proportion of GABA is made de novo to refill vesicles rather than ...

* Synthesized from **glutamate (Glu)** in a reaction catalyzed by glutamic acid decarboxylase (GAD) * Loaded and stored into vesicles by a vesicular GABA transporter, GAT (Gly uses the same transporter) * Cleared from synapse by **reuptake** using transporters on glia and neurons including non-GABAergic neurons * Higher proportion of GABA is made de novo to refill vesicles rather than **recycling** *

_GABA (y-aminobutyric acid) - inhibitory_ * Synthesized from glutamate (Glu) in a reaction catalyzed by ... ... ... (GAD) * Loaded and stored into vesicles by a ... ... transporter, GAT (Gly uses the same transporter) * Cleared from synapse by reuptake using transporters on glia and neurons including non-GABAergic neurons * Higher proportion of GABA is made de novo to refill vesicles rather than recycling

* Synthesized from glutamate (Glu) in a reaction catalyzed by **glutamic acid decarboxylase (GAD)** * Loaded and stored into vesicles by a **vesicular GABA** transporter, GAT (Gly uses the same transporter) * Cleared from synapse by reuptake using transporters on glia and neurons including non-GABAergic neurons * Higher proportion of GABA is made de novo to refill vesicles rather than recycling *

_Regulation of amino acid transmitter release_ * Too much .../ too little ... - hyper-excitability - epilepsy --\> excitotoxicity * Too much ... - sedation/coma

* Too much **Glu**/ too little **GABA** - hyper-excitability - epilepsy --\> excitotoxicity * Too much **GABA** - sedation/coma

_Cerebral ischemia - too much GLU_ * The metabolic events that retain the electrochemical gradient are abolished * Reversal of the Na+/K+ gradient * Transporters release ... from cells by reverse operation * ... -\> cell death (large increase of Ca2+ -\> enzymes -\> digestion of overexcited cells - death)

_Cerebral ischemia - too much GLU_ * The metabolic events that retain the electrochemical gradient are abolished * Reversal of the Na+/K+ gradient * Transporters release **glutamate** from cells by reverse operation * **Excitotoxic** -\> cell death (large increase of Ca2+ -\> enzymes -\> digestion of overexcited cells - death)

Cerebral ischemia - too much ...

Cerebral ischemia - too much **GLU**

GHB y-hydroxybutyrate (date rape drug) - too much ...

GHB y-hydroxybutyrate (date rape drug) - too much **GABA**

_GHB y-hydroxybutyrate (date rape drug) - too much GABA_ * A GABA metabolite that can be converted back to GABA * Increases amount of available GABA * Too much = ... and ...

* A GABA metabolite that can be converted back to GABA * Increases amount of available GABA * Too much = **unconsciousness and coma**

_The monoamines_ * ... - dopamine, epinephrine, norepinephrine * ... - serotonin

* **Catecholamines** - dopamine, epinephrine, norepinephrine * **Indolamines** - serotonin

_The monoamines_ * Catecholamines - ..., epinephrine, ... * Indolamines - ...

* Catecholamines - **dopamine**, epinephrine, **norepinephrine** * Indolamines - **serotonin**

_Catecholamine synthesis I_ * Dopamine synthesis occurs in ... steps

* Dopamine synthesis occurs in **2** steps

_Catecholamine synthesis II_

* DBH located in synaptic vesicles only, and NE is the only transmitter synthesised within vesicles

Administration of levodopa for treating what disease?

Parkinson's disease (Levodopa - converted to dopamine in brain - can cross blood brain barrier)

Levodopa - converted to dopamine in brain - can cross blood... ...

Levodopa - converted to dopamine in brain - can cross blood **brain barrier**

_Catecholamine storage_ * Loaded into vesicles by Vesicular ... ... (VMATs) (proton gradient like Glu and GABA transporters) * Modulation of catecholamine synthesis by drugs: * L-DOPA - Levodopa - precursor of ..., is used as a treatment for Parkinson's. Dopa decarboxylase converts it into ... increasing the pool of releasable transmitter

* Loaded into vesicles by Vesicular **monoamine transporters** (VMATs) (proton gradient like Glu and GABA transporters) * Modulation of catecholamine synthesis by drugs: * L-DOPA - Levodopa - precursor of **dopamine**, is used as a treatment for Parkinson's. Dopa decarboxylase converts it into **dopamine** increasing the pool of releasable transmitter

_Catecholamine release and reuptake_ * Released by Ca2+ dependant ... * Binds and activates ... * Signal terminated by ... into the axon terminal by transporters powered by electrochemical gradient (Dopamine transporters DATs, Norepinephrine transporters (NETs) etc) * In the cytoplasm - * ... back into vesicles * Enzymatically degraded by ... oxidases MAOs OR * Inactivated by catechol-O-methyl-transferase COMT

* Released by Ca2+ dependant **exocytosis** * Binds and activates **receptor** * Signal terminated by **reuptake** into the axon terminal by transporters powered by electrochemical gradient (Dopamine transporters DATs, Norepinephrine transporters (NETs) etc) * In the cytoplasm - * **Reloaded** back into vesicles * Enzymatically degraded by **monoamine** oxidases MAOs OR * Inactivated by catechol-O-methyl-transferase COMT

_Catecholamine release and reuptake_ * Released by Ca2+ dependant exocytosis * Binds and activates receptor * Signal terminated by reuptake into the axon terminal by transporters powered by electrochemical gradient (Dopamine transporters DATs, Norepinephrine transporters (NETs) etc) * In the cytoplasm - * Reloaded back into vesicles * Enzymatically degraded by ... OR * Inactivated by ...

* Released by Ca2+ dependant exocytosis * Binds and activates receptor * Signal terminated by reuptake into the axon terminal by transporters powered by electrochemical gradient (Dopamine transporters DATs, Norepinephrine transporters (NETs) etc) * In the cytoplasm - * Reloaded back into vesicles * Enzymatically degraded by **monoamine oxidases MAOs OR** * Inactivated by **catechol-O-methyl-transferase COMT**

_Modulation of catecholamine release and reuptake by drugs:_ * ... - reverses transporter so pumps out transmitter and blocks reuptake (DA and NE) * ... and Methylphenidate (Ritalin) blocks DA reuptake into terminals. More DA in synaptic cleft - extend into terminals. More DA in synaptic cleft - extended action on postsynaptic neuron * s... - MAO inhibitor found in dopaminergic nerve terminals thus preventing the degradation of DA allowing more to be released on subsequent activations (treatment of early-stage PD, depression and dementia) * ... - COMT inhibitor (treatment of PD)

* **Amphetamine** - reverses transporter so pumps out transmitter and blocks reuptake (DA and NE) * **Cocaine** and Methylphenidate (Ritalin) blocks DA reuptake into terminals. More DA in synaptic cleft - extend into terminals. More DA in synaptic cleft - extended action on postsynaptic neuron * **Selegiline** - MAO inhibitor found in dopaminergic nerve terminals thus preventing the degradation of DA allowing more to be released on subsequent activations (treatment of early-stage PD, depression and dementia) * **Entacapone** - COMT inhibitor (treatment of PD)

_Modulation of catecholamine release and reuptake by drugs:_ * Amphetamine - reverses transporter so pumps out transmitter and blocks ... (DA and NE) * Cocaine and Methylphenidate (Ritalin) blocks DA ... into terminals. More DA in synaptic cleft - extend into terminals. More DA in synaptic cleft - extended action on postsynaptic neuron * Selegiline - ... inhibitor found in dopaminergic nerve terminals thus preventing the degradation of DA allowing more to be released on subsequent activations (treatment of early-stage PD, depression and dementia) * Entacapone - ... inhibitor (treatment of PD)

* Amphetamine - reverses transporter so pumps out transmitter and blocks **reuptake** (DA and NE) * Cocaine and Methylphenidate (Ritalin) blocks DA **reuptake** into terminals. More DA in synaptic cleft - extend into terminals. More DA in synaptic cleft - extended action on postsynaptic neuron * Selegiline - **MAO** inhibitor found in dopaminergic nerve terminals thus preventing the degradation of DA allowing more to be released on subsequent activations (treatment of early-stage PD, depression and dementia) * Entacapone - **COMT** inhibitor (treatment of PD)

_Serotonin (5-HT)_ * Synthesis:

_Serotonin storage, release and reuptake_ * ... in vesicles * Signal terminated by ... by Serotonin transporters (SERTs) on presynaptic membrane * Destroyed by ... in cytoplasm

* **Stored** in vesicles * Signal terminated by **reuptake** by Serotonin transporters (SERTs) on presynaptic membrane * Destroyed by **MAOs** in cytoplasm

_Drugs modulating serotonin release and reuptake_ * ... (...) - blocks reuptake of Serotonin - SSRI - selective serotonin reuptake inhibitor - treatment of depression and OCD * ... stimulates the release of serotonin and inhibits it's reuptake - has been used as an appetite suppressant in the treatment of obesity * ... - methylenedioxymethamphetamine - ...: causes NE and serotonin transporters to run backwards releasing NT into synapse/extracellular space (Assessed for therapeutic potential in PTSD)

* **Fluoxetine** (Prozac) - blocks reuptake of Serotonin - SSRI - selective serotonin reuptake inhibitor - treatment of depression and OCD * **Fenfluramine** stimulates the release of serotonin and inhibits it's reuptake - has been used as an appetite suppressant in the treatment of obesity * **MDMA** - methylenedioxymethamphetamine - **Ecstasy**: causes NE and serotonin transporters to run backwards releasing NT into synapse/extracellular space (Assessed for therapeutic potential in PTSD)

_Drugs modulating serotonin release and reuptake_ * Fluoxetine (Prozac) - blocks reuptake of Serotonin - SSRI - selective serotonin reuptake inhibitor - treatment of ... and ... * Fenfluramine stimulates the release of serotonin and inhibits it's reuptake - has been used as an ... suppressant in the treatment of ... * MDMA - methylenedioxymethamphetamine - Ecstasy: causes NE and serotonin transporters to run backwards releasing NT into synapse/extracellular space (Assessed for therapeutic potential in ...)

* Fluoxetine (Prozac) - blocks reuptake of Serotonin - SSRI - selective serotonin reuptake inhibitor - treatment of **depression** and **OCD** * Fenfluramine stimulates the release of serotonin and inhibits it's reuptake - has been used as an appetite **suppressant** in the treatment of **obesity** * MDMA - methylenedioxymethamphetamine - Ecstasy: causes NE and serotonin transporters to run backwards releasing NT into synapse/extracellular space (Assessed for therapeutic potential in **PTSD**) *

_Acetylcholine - Ach_ * ... ... (ChAT, CAT) converts choline + acetyl CoA (coenzyme A) into acetylcholine * Packed into vesicles by ... acetylcholine ... (VAChT) * Rapidly ... in synaptic cleft by Acetylcholinesterase (AChE) * Choline is transported back into the presynaptic terminal and converted to acetylcholine

* Choline Acetyltransferase (ChAT, CAT) converts choline + acetyl CoA (coenzyme A) into acetylcholine * Packed into vesicles by **vesicular** acetylcholine **transporter** (VAChT) * Rapidly **degraded** in synaptic clef by Acetylcholinesterase (AChE) * Choline is transported back into the presynaptic terminal and converted to acetylcholine

_Acetylcholine - Ach_ * Choline Acetyltransferase (ChAT, CAT) converts ... + acetyl CoA (coenzyme A) into acetylcholine * Packed into vesicles by vesicular acetylcholine transporter (VAChT) * Rapidly degraded in synaptic cleft by ... (AChE) * Choline is transported back into the presynaptic terminal and converted to acetylcholine

* Choline Acetyltransferase (ChAT, CAT) converts **choline** + acetyl CoA (coenzyme A) into acetylcholine * Packed into vesicles by vesicular acetylcholine transporter (VAChT) * Rapidly degraded in synaptic clef by **Acetylcholinesterase** (AChE) * Choline is transported back into the presynaptic terminal and converted to acetylcholine

_Drugs modulating acetylcholine degradation_ * AChE (acetylcholinesterase) ... * Blocks the breakdown of Ach, prolonging its actions in the synaptic ... e.g. neostigmine (treatment of myasthenia gravis, MG) * Positive - helps with ... of disease

* AChE (acetylcholinesterase) **inhibitors** * Blocks the breakdown of Ach, prolonging its actions in the synaptic **cleft** e.g. neostigmine (treatment of myasthenia gravis, MG) * Positive - helps with **symptoms** of disease

_AChE (acetylcholinesterase) inhibitors_ * Blocks the breakdown of Ach, prolonging its actions in the synaptic cleft e.g. ... (treatment of myasthenia gravis, MG) * Positive - helps with symptoms of disease

* Blocks the breakdown of Ach, prolonging its actions in the synaptic cleft e.g. **neostigmine** (treatment of myasthenia gravis, MG) * Positive - helps with symptoms of disease

_Neuropeptides_ * ... transmission * Vary in their methods of ... and release from small molecule transmitters * ... polypeptide chains - 3-36 amino acids * Over one hundred neuropeptides described * E.g. endorphins, neuropeptide Y, substance P, endogenous opioids, vasopressin

* **Slow** transmission * Vary in their methods of **synthesis** and release from small molecule transmitters * **Short** polypeptide chains - 3-36 amino acids * Over one hundred neuropeptides described * E.g. endorphins, neuropeptide Y, substance P, endogenous opioids, vasopressin

_Neuropeptides_ * Slow transmission * Vary in their methods of synthesis and release from small molecule transmitters * Short polypeptide chains - 3-36 amino acids * Over one hundred neuropeptides described * E.g. e..., neuropeptide Y, substance P, endogenous opioids, v...

* Slow transmission * Vary in their methods of synthesis and release from small molecule transmitters * Short polypeptide chains - 3-36 amino acids * Over one hundred neuropeptides described * E.g**. endorphins, neuropeptide Y, substance P, endogenous opioids, vasopressin**

_Neuropeptide release and degradation_ * Follow the ... pathway and NOT released in the same manner as small molecule transmitters * Dense core vesicle fusion and ... occurs as a result of global elevations of Ca2+ (sustained or repeated depolarization or release of Ca2+ from intracellular stores) * Neuropeptide vesicle membrane ... but not refilled * Bind to and activate ... * Neuropeptides signalling is terminated by diffusion from site of release and degradation by .. in the extracellular environment * Release is ... than small molecule release and signals may be maintained for ...

* Follow the **secretory** pathway and NOT released in the same manner as small molecule transmitters * Dense core vesicle fusion and **exocytosis** occurs as a result of global elevations of Ca2+ (sustained or repeated depolarization or release of Ca2+ from intracellular stores) * Neuropeptide vesicle membrane **recycled** but not refilled * Bind to and activate receptor * Neuropeptides signalling is terminated by diffusion from site of release and degradation by **proteases** in the extracellular environment * Release is **slower** than small molecule release and signals may be maintained for **longer**

_Neuropeptide release and degradation_ * Follow the secretory pathway and NOT released in the same manner as small molecule transmitters * Dense core ... ... and exocytosis occurs as a result of global elevations of ...+ (sustained or repeated depolarization or release of ...+ from intracellular stores) * Neuropeptide vesicle membrane recycled but not refilled * Bind to and ... receptor * Neuropeptides signalling is terminated by diffusion from site of release and degradation by proteases in the ... environment * Release is ... than small molecule release and signals may be maintained for longer

* Follow the secretory pathway and NOT released in the same manner as small molecule transmitters * Dense **core vesicle** fusion and exocytosis occurs as a result of global elevations of **Ca2**+ (sustained or repeated depolarization or release of **Ca2**+ from intracellular stores) * Neuropeptide vesicle membrane recycled but not refilled * Bind to and **activate** receptor * Neuropeptides signalling is terminated by diffusion from site of release and degradation by **proteases** in the **extracellular** environment * Release is **slower** than small molecule release and signals may be maintained for longer

_Other transmitters/ retrograde signalling_ * Soluble gases - Nitric oxide and carbon monoxide * NO made in ... neuron by Nitric oxide synthase (activated by the binding of Ca2+ and calmodulin) * The gas is not ... but rapidly diffuses from it's site of synthesis. Diffuses between cells (into presynaptic cell - retrograde transmitter) * Activates guanylyl cyclase which makes the ... messenger cGMP * Within a few seconds of being produced NO is converted to biologically ... compound (Switching off the signal) * Potentially useful for coordinating activities of multiple cells in a small region (tens of micrometers) how big is a neuron?

* Soluble gases - Nitric oxide and carbon monoxide * NO made in **postsynaptic** neuron by Nitric oxide synthase (activated by the binding of Ca2+ and calmodulin) * The gas is not **stored** but rapidly diffuses from it's site of synthesis. Diffuses between cells (into presynaptic cell - retrograde transmitter) * Activates guanylyl cyclase which makes the **second** messenger cGMP * Within a few seconds of being produced NO is converted to biologically **inactive** compound (Switching off the signal) * Potentially useful for coordinating activities of multiple cells in a small region (tens of micrometers) how big is a neuron?

_Other transmitters - retrograde signalling_ * Endocannabinoids * Small lipids which mostly cause reduced ... release at certain inhibitory terminals * A cannabinoid is also the active component of ...

* Endocannabinoids * Small lipids which mostly cause reduced **GABA** release at certain inhibitory terminals * A cannabinoid is also the active component of **marijuana** (Cannabis sativa)

Chemicals in the Brain Flashcards

(58 cards)