Neurotransmitters Flashcards
Discuss Type 1 asymmetric synapse.
WIde cleft
Large postsynaptic density
Asymmetric conformation between synaptic cleft and active zone
type 1 at the spine of dendrites and shaft
Usually excitatory- glutamate
Discuss Type 2 symmetric cleft.
- tiny active zone
- narrow synaptic cleft
- symmetric conformation between synaptic cleft and active zone
- cell bodies are where GABA functions much closer to the axon hillock)
Usually inhibitory
Define neurotransmitters.
Chemical substance
end of nerve fibers
from nerve impulse
Transfers impulse to target structure, via diffusion through synapse.
Give examples of Amines.
Serotonin
Acetylcholine
Melatonin
Histamine
Give examples of Catecholamines.
Dopamine
Norepinephrine
Epinephrine
Give examples of peptides.
Substance P
Oxytocin
Vasopressin
Somatostatin
Neuropeptide Y
Cholecystokinin
Give examples of Amino Acids.
GABA (γ-amino-butyric acid)
Glutamate
Glycine
Aspartate
Give examples of Purines.
ATP
Adenosine
Compare the synthesis of and storage of other neurotransmitters such as amino acids and amines to peptides.
All neutrasmitters synthesizes from precursor molecule (ribosomes/REE) -> move to golgi apparatus (vesicle packaging) -> Taken to end terminals via microtubular cytoskeleton (motor enzymes called kinesins) ->
However peptides Does not get packaged in golgi but in cytosol where an array of enzymes split it into finished neurotransmitter -> travels to end terminals where further packaged into vesicles.
What is the function of the endosome?
Endosome is a quality check. Houses as a pool till vesicles need transmitters to form.
What is clathrin?
Allows the endosome to identify the vesicle.
What is the function of dynamin?
Budding off of vesicles to endocytose.
What is difference between the classical and kiss and run mechanism of vesicles?
Classical- clathrin attaches and vesicle returns to endosome.
Kiss and run- only budding off and waits in the pre-synaptic vesicle.
Describe how an ionotropic (direct gating) works.
Neurotransmitters bind to the gate and this causes a conformation change.
Allows the influx of ions it is permeable to.
Describe the mechanism of action of metabotropic channels.
Receptor connected to a G protein.
Activates adenylyl cyclase and this produces cAMP
Produces protein kinase and this phosphorylate K+ channels
What is the life cycle of ACh?
Choline + Acetyl CoA
ChAT
removed via AChE
Where is ACh released from?
Motor neurons- somatic function
Autonomic nervous system
basal forebrain, through the cerebral cortex, neuromodulator
Describe the action of ACh that is released from somatic motor neurons.
They are released and bound to the nicotinic receptors,
there are plenty of nicotinic receptors to ensure that a response is elicited.
Describe the action of ACh in the autonomic nervous system.
Sympethatic innervation of medulla- ACh- nicotinic receptor of the adrenal medulla- release E
Sympathetic- Pre-gan- ACh- NR- Post-gan- NE
Parasympathetic- ACh- NR- ACh- Muscarinic
What are the 2 receptors of ACh?
Nicotinic and Muscarinic
Explain the effect of the ACh on muscarinic receptors.
ACH binds to receptor -> G-protein activation -> G-protein (beta-gamma) subunits bind to potassium channel and cause it to open, causing eflux of potassium ions -> hyperpolarization of cell -> takes membrane potential away from hyperpolarization to inhibit action potential
Discuss Alzheimer’s Disease.
Cholinergic neurons in the basal forebrain are some of the first neurons to die.
(damage causes no release of ACH in that region
-> synapse does not work, leading to neuronal cell death. Sign of Alzheimer’s disease in basal forebrain/hippocampal region)
What is the management of Alzheimer’s?
AChE inhibitors: Rivastigmine
How can Botulinum toxin cause paralysis?
Botox destroys the SNARE complex and no exocytosis of synaptic vesicles.
ACh has not been released.
No ACh for muscle contraction
Name the ions that can pass through the nicotinic receptors.
Na+ and K+
What is Dale’s Principle?
neuron performs the same chemical action at all of its synaptic connections to other cells, regardless of the identity of the target cell.
As a result, the effect depends on the receptor.
Which neurotransmitter is considered to be the major excitatory NT in the brain?
Glutamate
Name the class of receptors that glutamate binds to.
Ionotropic/ direct gating
What are glutamate receptors permeable to?
Na+ and K+
Name the glutamate receptors.
NMDA- also permeable to Ca2+
AMPA-
Kainate
Why is the AMPA receptor faster than the others?
fast transduction is due to it having a non-receptor component that causes downstream intracellular changes inside cells- MAP kinase? Which causes a stronger synaptic response.
Magnesium plugin NMDA blocks the flow of ions in NMDA and causes a slower response to ions. Requires more depolarization to open up the plug
What is the purpose of the NMDA?
Slow kinetics for long-term synaptic potentiation and depression
Explain the structure of NMDA receptors.
Has amino acid residues that attract Mg 2+, when the receptor is depolarized.
The ions only move through the receptor once the membrane is depolarised.
How do the NMDA receptors ensure learning and memory?
It is permeable to Ca2+ and this activates 2nd messengers.
Also this opens AMPA receptors and further depolarised.
Describe the metabotropic glutamate receptors.
This G-Protein activates a Diacylglycerol-inositol triphosphate second messenger cascade
Describe the life cycle of glutamate
Glutamine via glutaminase to glutamate. packing into vesicles via VGLUT channels.
Taken up via EAAT on neuron and glial cells.
in glial cells broken back down to glutamine synthetase and leaves via SN1 and enters neuron via SAT2
What is the relationship between cerebral ischemia and glutamate excitotoxicity?
(no blood flow. neurons cannot receive nutrients -> Damage/death -> release of all glutamate within it (sustained release) -> sustained binding of glutamate to its receptors -> membrane potential more positive, Mg+ plug leaves receptor -> influx of calcium ions -> apoptotic pathways activated by increased in calcium -> activation of enzymes to break down cellular components till cell death occurs)
What is the function of GABAnergic neurons and where are they found?
Regulate the firing rate if AP
Medium spiny neurons of the striatum and Cerebellar Purkinje cells
Discuss the life cycle of GABA
GAD removes carboxylate group from glutamate to form GABA -> loading into vesicle via VIAAT channels -> once action potential arrives influx of calcium -> docking -> Gaba release into cleft -> Bind to GABA receptors
GAT channels allow the re-uptake, which is sodium-dependent.
What are the types of GABA receptors?
GABA-a: ligand-gated anion channels. Fast IPSP
GABA-b receptors- Metabotropic. Slow and coupled to K+
Describe the extracellular view of GABA-a receptors.
Between alpha 1 and beta 2 proteins is the location of GABA-site
between gamma 2 and alpha 1 is the location of BZd site.
Describe the action that follows GABA binding to the GABA-a receptors.
The influx of Cl- ions into the cell after the opening of the chloride pore.
Makes outward current more positive and inward current more negative. hyperpolarization. prevents generation of action potential
KCC2 is a transport. Maintains concentration of Cl on either side of the membrane. prevents
drastic changes on chloride concentration
Describe the 2 mechanisms of synaptic inhibition.
Hyperpolarizing inhibition
– If the GABAAR reversal potential is hyperpolarized
to the membrane potential
Shunting inhibition
– If the GABAAR reversal potential is equal or slightly
positive of the membrane potential, not significant change.
Describe how GABA can generate an excitatory response.
excitatory post-synaptic potential achieved
as the equilibrium potential is above the threshold.
What is the function of GABA in embryological development?
Depolarizing GABA responses during development produce electrical activity that controls neuronal proliferation,
migration, growth, and maturation, as well as determining synaptic connectivity.
Once these developmental processes are completed, the resulting neural circuitry requires inhibitory transmission that
can then also be provided by GABA.
What role does Cl- play in epileptic seizures?
before an epileptic response, normal Cl- level. During the seizure, the massive influx of cl into neurons in a short period of time, shifts equilibrium potential to a positive one very quickly, causing Gaba to become excitatory and trigger action potentials - the larger the Cl the longer the seizure
What is the common effect of NE, serotonin and Dopamine?
Mood
Cognitive function
What is the common effect of Serotonin and Dopamine?
Appetite, sex and aggression
What is the common effect of Serotonin and Dopamine?
Appetite, sex and aggression
What is the common effect of NE and Dopamine?
Attention
What is the effect of serotonin?
Obsessions, compulsions and memory
What is the effect of NE?
Alertness, concentration and energy
What is the effect of dopamine?
Pleasure, reward and Motivation
Describe the life cycle of serotonin.
Tryptophan (Tryptophan hydroxylase) to 5HTP (5HTP decarboxylase): permeable to BBB- Serotonin
Removed from synapse via SERT transporters, either reloaded or broken down via MAO- monoamine oxidase.
Where is Serotonin released from?
Raphe nuclei
Where does serotonin project to?
– Amygdala
– Basal Forebrain
– Hypothalamus
– Thalamus
– Hippocampus
– Cerebral Cortex
Outline the clinical applications of serotonin levels.
– Antidepressants elevate synaptic serotonin levels
– Aggression has been linked to high serotonin levels
– Serotonin is a precursor to melatonin which is NB for sleep patterns
– Some antidepressants lead to loss of appetite
– Serotonin receptors in spinal cord inhibit pain pathways
Describe the 5HT1f receptor.
Sumatriptan can bind
G-protein
cerebral cortex, dorsal raphe, hippocampus
Describe how antidepressants elevate serotonin.
- Blocking transporter for reuptake
- Blocking the catabolic enzyme (MAO)
Increase at synapse
Describe the 5HT2a receptor.
Agonist LSD- psychedelics
Antagonist, atypical antipsychotics
cerebrum and basal ganglia
Gprotein
Describe the 5HT3 receptor.
Antiemetics (Ondansetron)
– Antagonist
block nausea and vomiting
Ligand-gated channel
Describe the life cycle of Catecholamines.
Tyrosine (tyrosine hydroxylase)- Dopa (Dopa decarboxylase)- Dopamine (DBH)-NE (PNMT)-E
Discuss dopamine in the nigrostriatal pathway.
- Origin: Substantia nigra(midbrain)
- Projection: Striatum
- Function: Movement
- Disease: Parkinson’s Disease, Other movements
disorders
Discuss dopamine in the mesolimbic pathway.
- Origin: Ventral tegmental area
- Projection: Limbic System, Nucleus accumbens, Amygdala Hippocampus
- Function: Motivation Desire
Disease: - Addiction- reward pathway
- Schizophrenia
- Depression
- ADHD
Discuss dopamine in the mesocortical pathway.
Origin:
* Ventral tegmental area
Projection:
* Cortex
* Frontal Lobe
Function:
* Motivation in cognition
* Motivation in sensation
* Conscious emotion
Disease:
* Schizophrenia
* ADHD
Discuss dopamine in the Tuberinfundibular Pathway.
Origin:
* Arcuate Nucleus
(Hypothalamus)
Projection:
* Pituitary
* Posterior Lobe
Function:
* Regulation of prolactin
release
Which dopamine receptors activate adenylate cyclase?
D1 and D5
D2, D3 and D4 inhibits
Explain the effects of caffeine on dopamine.
blocks re-uptake of dopamine.
What are the effects of methamphetamine on dopamine?
reverses the action of the transporter, which then actively pumps out more dopamine
Anything that messes with your dopamine system will be addictive.
