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What is an example of when a molecule is acting as a neuromodulator?
A molecule is released into the extracellular fluid and activates the presynaptic autoreceptor of a synapse to regulate neurotransmitter release.
TYPE: Cholecystokinin
Type 4: Neuropeptides.
TYPE: Glycine
Type 2: Amino Acids
TYPE: GABA
Type 1: Classical Neurotransmitters
TYPE: Nitric Oxide
Type 3: Gaseous Messengers
TYPE: Dopamine
Type 1: Classical Neurotransmitters
TYPE: Glutamate
Type 2: Amino Acids
TYPE: ATP
None.
TYPE: Enkephalin
Type 4: Neuropeptides
T/F: A molecule must have all of the following characteristics to be considered a neurotransmitter...
It must have a mechanism of termination.
True.
T/F: A molecule must have all of the following characteristics to be considered a neurotransmitter...
It must be released after a neuron is stimulated.
True.
T/F: A molecule must have all of the following characteristics to be considered a neurotransmitter...
It must be uniquely synthesized in the presynaptic terminal.
False.
T/F: A molecule must have all of the following characteristics to be considered a neurotransmitter...
It must mimic the action of the nerve being stimulated.
True.
Name some neurotransmitters store in small clear synaptic vesicles.
Histamine and glycine.
A small molecule neurotransmitter that is uniquely synthesized within a specific neuron is an example of a…?
Type 1: Classical Neurotransmitter
A large molecule neurotransmitter that is stored in large dense-core vesicles in an example of a…?
Type 4: Neuropeptides
A small molecule neurotransmitter that is not uniquely synthesized within a specific neuron is an example of a…?
Type 2: Amino Acids
What is an enzyme that is important for the synthesis of Acetylcholine and can work in both directions of the reaction?
Choline Acetyl Transferase.
In his famous experiment, ________ identified a chemical that he called vagusstoff which was released when he stimulated the vagus nerve of a frog heart. Interestingly, when he applied the same fluid from the first frog heart to a second one in a completely separate chamber, it caused the heart rate to decrease.
Otto Lowei.
STEP ONE: acetylcholine synthesis and storage from precursors used to synthesize ACh to its storage.
Choline is transported into the cell through the HACU transporter.
STEP TWO: acetylcholine synthesis and storage from precursors used to synthesize ACh to its storage.
Acetyl CoA and Choline are processed by ChAT to produce ACh.
STEP THREE: acetylcholine synthesis and storage from precursors used to synthesize ACh to its storage.
V-ATPase pumps protons into the synaptic vesicle.
STEP FOUR: acetylcholine synthesis and storage from precursors used to synthesize ACh to its storage.
VAChT uses the proton gradient to push ACh into the vesicle.
What proteins are specific to cholinergic neurons and can therefore be used as markers or a way to genetically manipulate them?
Vesicular Acetylcholine Transporter (VAChT) and Choline Acetyl Transferase (ChAT).
What is an agonist for acetylcholine?
Inhibiting acetylcholinesterase.
T/F: Monoamine neurotransmitters always have a catechol group
False.
T/F: Serotonin is a monoamine
True.
T/F: Dopamine is a monoamine
True.
T/F: Monoamine neurotransmitters always contain an amine group
True.
Match the neuron with the neurotransmitter it releases in the ANS:
Pre-ganglionic neurons in the Sympathetic Division of the ANS
Acetylcholine.
Match the neuron with the neurotransmitter it releases in the ANS:
Pre-ganglionic neurons in the Parasympathetic Division of the ANS
Acetylcholine.
Match the neuron with the neurotransmitter it releases in the ANS:
Post-ganglionic neurons in the Sympathetic Division of the ANS innervating the Heart
Norepinephrine.
Match the neuron with the neurotransmitter it releases in the ANS:
Post-ganglionic neurons in the Parasympathetic Division of the ANS innervating the Sweat Glands
Acetylcholine.
Which neurotransmitters require the enzyme Aromatic Amino Acid Decarboxylase for their synthesis?
Norepinephrine, epinephrine, serotonine, and dopamine.
What is the BEST protein that can be used to selectively target neurons that release each monoamine? Serotonin
Tryptophan Hydroxylase (TPH).
What is the BEST protein that can be used to selectively target neurons that release each monoamine? Dopamine
Dopamine Selective Transporter (DAT).
What is the BEST protein that can be used to selectively target neurons that release each monoamine? Epinephrine
Phenylethanolamine-N-methyltransferase (PNMT).
What is the BEST protein that can be used to selectively target neurons that release each monoamine? Norepinephrine
Norepinephrine/Epinephrine Transporter (NET) with absence of PNMT.
What is the BEST protein that can be used to selectively target neurons that release each monoamine? Histamine
Histidine Decarboxylase.
The signaling from dopamine is kept rapid by...
Reuptake by DAT, termination with Catechol-O-Methyltransferase (COMT), and termination with Monoamine Oxidase (MAO) A.
Glutamate is…?
a Type 2 Amino Acid transmitter and is stored in small clear vesicles and released by exocytosis.
Alpha-ketoglutarate is converted to glutamate by the enzyme…?
Glutamate dehydrogenase.
Alpha-ketoglutarate can also react with aspartate to create glutamate with the enzyme…?
Aspartate aminotransferase.
Astrocytes can take up glutamate and break it down using the enzyme glutamine synthetase to create gultamine which is shuttled back to the presynapse and converted back into glutamate using the enzyme…?
Glutaminase.
A protein that is specific to Glutamatergic neurons is…?
Vesicular Glutamate Transporter (VGLUT).
Which glutamate receptor is metabotropic and acts on the cAMP pathway?
mGluR2.
How does glutamate act in an inhibitory manner through mGluR6 in the retina?
Through downstream signaling which closes the TRPM1 channel to hyperpolarize the cell.
GABA is…?
An amino acid and is uniquely synthesized by GABAergic neurons.
In developing neurons, GABA can ________ the cell because there is a special transporter expressed that pushes chloride into the cell, making the driving force of this ion outward when GABA binds to its GABAA receptor.
Depolarize.
What protein is only expressed by neurons that release GABA?
Glutamate Decarboxylase (GAD).
GABA agonist drugs can act by...?
blocking GABA Transporters (GAT) and inhibition of the activity of GABA-Transaminase (GABA-T).
What protein is only expressed by neurons that release Glycine?
GLYT-2.
Neuropeptides are stored in…?
Dense Core Vesicles.
Small Molecule Neurotransmitters are stored in…?
Small Clear Vesicles.
Match the synthesis of neuropeptides in their appropriate locations within the neuron.
Transcription of the mRNA from the Gene
Cell nucleus.
Match the synthesis of neuropeptides in their appropriate locations within the neuron.
Translation of the Pre-Propeptide
Rough ER.
Match the synthesis of neuropeptides in their appropriate locations within the neuron.
Shortened to a Propeptide
Golgi apparatus.
Match the synthesis of neuropeptides in their appropriate locations within the neuron.
Cleaved into Neuropeptides
Dense core vesicles.
Neuropeptide synthesis can be increased with high neural activity through increased intracellular calcium leading to…?
increased transcription of pre-propeptide genes and translation of neuropeptides.
What was the first discovered neuropeptide?
Substance P.
ATP as a neurotransmitter…?
co-released with almost all neurotransmitters, and binds to Purinergic receptors.
The history of opioids is interesting because...
Morphine was first isolated the Opium poppy, opioid receptors were discovered before endogenous ligands, and Opium was originally used for many therapeutic purposes (even in babies to treat colic).
Match the opioid receptor with its unique feature. Mu receptor
causes euphoria.
Match the opioid receptor with its unique feature. Kappa receptor
Is the least likely to cause drug abuse.
Match the opioid receptor with its unique feature. Delta receptor
binds to enkephalins.
All currently known opioid receptors are…?
G protein coupled receptors.
One reason why opioids can become addictive is because of drug tolerance. This works in the brain by:
With chronic use, opioid receptors become endocytosed resulting in less receptors to bind to the drug.
The reward pathway underlies motivated behaviors and addiction. The ___________ which responds to cues and the reward is first activated. It releases dopamine onto the Nucleus Accumbens which is important for the feeling of euphoria and its neurons project to the prefrontal cortex where they also releases dopamine.
Ventral Tegmental Area.
In vascular smooth muscle, Nitric Oxide acts on ____________ which converts GTP to cGMP that acts on myosin LC phosphatase to dephosphorylate myosin LC leading to muscle relaxation.
Guanylyl Cyclase.
Nitric Oxide is synthesized from Arginine with the enzyme __________ which also generates citrulline.
Nitric Oxide Synthase.
Endocannabinoids and Gaseous Neurotransmitters are similar because they both...
not stored in vesicles.
What is the mechanism of action of Cannabidiol (CBD)?
Weak antagonist of CB1 and CB2 receptors and Agonist of TRPV1 receptors
The founder of CWRU Neurosciences Department is credited with the discovery that neurons can switch their phenotype from adrenergic neurons to cholinergic neurons in a famous experiment called "The Cholinergic Switch". Who is this famous scientist?
Story Landis.
In these experiments, neurons in early development (P7) expressed proteins typical of noradrenergic neurons such as __________ , but as they developed (P21), they started to down-regulate expression of these proteins and up-regulate expression of proteins typical of cholinergic neurons such as vasoactive intestinal peptide . This is an example of the cholinergic switch occurring naturally in the body.
tyrosine hydroxylase.
Nerve growth factor can…?
the first neurotrophic factor to be discovered, activate the phosphoinositol pathway, and binds to TrkA which is a type of metabotropic receptor.
RELEASE TYPE: A synaptic vesicle contains both GABA and Glycine
Corelease.
RELEASE TYPE: A neuron secretes Glutamate from small clear vesicles and a neuropeptide from dense core vesicles
Differential release.
RELEASE TYPE: A synaptic vesicle contains ATP and Dopamine
Corelease.
RELEASE TYPE: A neuron secretes norepinephrine from one axon branch and acetylcholine from another axon branch
Spatial segregation.
One of the most important jobs Astrocytes have is to regulate extracellular potassium in the CNS because high levels of extracellular potassium...
Will drive potassium into the cell, change its equilibrium potential, and cause the cell to be depolarized.
Most adult mammalian neurons are enveloped by an astrocyte creating a…?
Tripartite synapse.
Astrocytes are currently recognized for their role in...
Reuptake of potassium in the extracellular space, forming and eliminating synapses, adding glutamate to the extracellular fluid to maintain concentrations, and releasing gliotransmitters to communicate with neural cells.
T/F: Astrocytes have changes in their membrane potentials.
True.