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Neurotransmitters - Coggle Diagram
Neurotransmitters
*GABA
(Gamma aminobutyric acid)
Recreational Drugs
Alcohol
--> GABA agonist
Benzodiazapines
--> think
BENZ
= fre
QUENZ
y of GABA receptors
Barbituates
--> think barbi
DUR
ates =
DURation
of GABA receptors
GABA Re-Uptake
the GABA cycle requires both the
--> excitatory EAAT transporter for glutamine intermediate
--> inhibitory VIAAT transporter for vesicle packaging
#4 - EAAT Transporter
EAAT = excitatory amino acid trasnporter
--> just like in Glutamate cycle it brings Glutamine from astrocyte to GABA neuron this time
#2 - Mitochondria breakdown of GABA
mitochondria breaks down GABA
--> think that once in glial cell (astrocyte) GABA must convert to glutamate and finally glutamine to get back to the GABA-neuron
mitochondria converts GABA to alpha-ketoglutarate
--> alpha-ketoglutarate --> glutamate
#6 - VIAAT
VIAAT = vesicular inhibitory amino acid transporter
--> packages GABA into vesicles for release
#3 - Glutamine Synthase
glutamine synthase makes glutamine from glutamate
#1 - GAT on Glial cell + GABA-neurons
GAT = GABA transporter
--> similar pathway to Glutamine since GABA made from Glutamine
GAT brings GABA into astrocytes
GAT also directly can reuptake GABA to repackage
#5 - GLU-DEC = GAD
GLU-DEC = glutamine decarboxylase
--> converts glutamate into GABA
Actions/Pathways
GABA Receptors
either sub-type A or B
both hyperpolarize the cell either by the two main hyperpolarizing ions Cl- and K+:
--> Cl- ions in
--> K+ ions out
GABA-b Receptors
metabotropic
--> means they are GPCR = G-protein coupled receptors
--> think metabo has a B in it
allow K+ ions out of cell
--> hyperpolarize the cell
--> cause inhibition of APs
GABA-a Receptors
Ionotropic receptors
--> means they directly allow in ions
allow in Cl- ions
--> hyperpolarize the cell
--> cause inhibition of APs
Neurotransmitter and Synthesis
main inhibitory NT of CNS
GABA is made from glutamate
--> Glutamate is a self regulating NT since if too much is made, it can be converted into GABA to inhibit itself
Glu-Dec = glutamate decarboxylase
--> converts glutamate into GABA
--> think if you get too excited in making boards for a deck
-->
you need to "GLU the DECK"
*ACh = Acetylcholine
ACh Receptors
muscarinic ACh receptors
metabotropic = GPCR
nicotonic ACh receptors
ionotropic receptors that are non-specific for cations
--> Ca2+, Na+, K+
ACh Re-Uptake
#3 - CAT enzyme = Choline Acetyl Transferase
CAT enzyme transfers an acetyl group from the Citric acid cycle of mitochondria onto the choline
--> makes ACh
#4 - VAT = Vesicular ACh Transporter
VAT brings ACh into vesicles so it can be released at the terminal
#1 - ACh Esterase
Acetyl choline esterase breaks down ACh in the synaptic cleft into:
--> Choline group + acetyl group
#2 - Na+/Choline Cotransporter
Choline is brought back into the cell with Na+ that is in excess outside the cell
Recreational Drugs
ACh Synthesis
ACh made in the brainstem
*Glutamate (Glu)
Glutamate synthesis
amino acid NT
--> absorbed through diet
--> cannot pass the BBB
--> synthesized in the CNS by alpha-ketogluterate from Citric Acid Cycle = Krebb's Cycle
note glutamate can be converted to GABA
--> this is a self regulating NT since if too much is made, it can be converted into GABA to inhibit itself
Glutamate
Receptors
ALL main glutamate
receptors are ionotropic
AMPA Receptors
allow in BOTH Na+ and K+ ions
--> think Glu main excitatory ion
--> Na+ and K+ main NTs for APs
--> only a small # of K+ actually pass through
AMPA receptors are the main Glutamate receptors
they give fast AP conduction
NMDA ligand gated (Mg+) Ion Receptors
AMPA are the same as NMDA receptors since they allow both Na+ and K+
--> NMDA also allow Ca2+ though
NMDA receptors are used to modulate AMPA receptors
NMDA receptors are also needed in learning and memory
note NMDA receptors are gated by Mg+ ions
--> the Mg+ doesn't move unless AMPA receptors on post synaptic cell have caused enough depolarization for the regulatory NMDA to kick in
NMDA mneumonics
--> NM = need more ions = also let in Mg+ ions
--> NM = need memories
--> Need modulation
NMDA Glutamate receptors and LTP
LTP = long term potentiation
note by NMDA also allowing in Ca2+ in addition to Na+ and K+ from AMPA
--> think NM in NMDA = Need Memory!
Ca2+ binds to calmodulin nd activates Ca2+/Calmodulin dependent protein kinase 2
Ca2+ causes plasticity and strengthening of synapse
Ca2+ also causes more AMPA receptors to go to the cell membrane to increase the response
Kainate Receptors
Glutamate Re-uptake
= Glutamate > Glutamine Cycle
#2 - Glutamine synthetase
enzyme in glial cells (mostly astrocytes)
converts Glutamate into Glutamine
--> think this is necessary to convert to Glutamine
--> Glutamine is not a NT and thus will be safely transported back to the Glutaminergic neuron without binding to anything
#5 - VGLUT
VGLUT = Vesicular Glutamate
transports Glutamate into vesicles for release
#4 - Glutaminase
enzyme in glutaminergic cells (mostly astrocytes)
breaks down Glutamine into Glutamate
--> changes amide group into carbonic acid group
#3 - EAATs (on glutaminergic neuron)
Excitatory Amino Acid Transporters on glutaminergic pre-syn neurons
EAATs can also transport glutamine
need to get back into glutaminergic neuron to synthesize more glutamate
#1 - EAATs (on glial cell)
Excitatory Amino Acid Transporters
--> remember the main excitatory NT = glutamate
--> it must be
EATEN UP
quickly before it excites too much
present mainly on glial cells (mostly astrocytes)
--> also present on glutaminergic pre-syn neurons
transport glutamate out of the cleft after use into astrocytes
Drugs
*Glycine
inhibitory NT
mainly in the brainstem and spinal cord
Glycine Re-Uptake
#1 - GLAT
GLAT = Glycine transporter
transports Glycine
directly
back into the glycinegetic neuron
--> NO re-uptake intervention by glial cells like in Glutamate
#3 - VIAAT = vesicular inhibitory Amino acid transporter
note VIAAT is the same transporter for vesicles as GABA since they are both inhibitory
#2 - SeTHM = serine transhydroxymethylase enzyme
SETHM converts serine into glycine
Recreational Drugs
Glycine Receptors
-
Glycine Synthesis
-
*monoamines
dopamine, NE, and 5 HT = serotonin
*Dopamine (DA)
SIMPLE 2 step process like Serotonin
also uses the same VMAT as serotonin
Dopamine Synthesis
monoamine made from tyrosine
--> think of
TYRONE the drug dealer
--> TYRONE sells dopamine
tyrosine
--> L-DOPA
--> dopamine
--> NE = norepinephrine
--> Epi = epinephrine
tyrosine hydroxylase converts tyrosine into dopamine
--> think TYRONE also sells alcohol
--> hydroxylase needed to form dopamine
4 Dopamine Pathways
Nigro-Striatum DA Pathway
substantia nigra (midbrain) --> striatum (caudate + Putamen)
--> remember striatum as mix of a STRAIGHT CAUTIOUS DATER + PutaMEN
--> Striatum = Caudate + Putamen
MesoCortical DA Pathway
VTA = Ventral Tegmental Area (midbrain) --> Frontal cortex (mainly the prefrontal cortex)
MesoLimbic DA Pathway
VTA = Ventral Tegmental Area (midbrain) --> Nucleus Accumbens (also to other limbic structures)
--> remember
"V-TA DA-NA"
song makes DANA very positive, happy and hallucinate
Tuberoinfundibular --> Prolactin DA Pathway
Infundibulum (= pituitary stalk of hypothalamus) --> anterior pituitary gland (causes release of prolactin)
Dopamine/Catecholamine Breakdown
MAO and COMT
think that MAO is a COMMUNIST CAT
--> MAO is in the mitochondria
--> COMT is in the cytosol
MAO = Monoamine oxidase
MAO breaks down catecholamines (NE mainly) in the mitochondria
also breaks down these NTs:
--> histamine
--> serotonin
--> NE
MAO inhibitors used to treat depression due to the monoamine theory of depression
--> note MAO inhibitors can cause hypertension since they stop NE breakdown in the periphery
MAO B
mainly used for Dopamine breakdown
MAO A
mainly used for 5HT and NE breakdown
COMT = catechol-o-methyl transferase
COMT breaks down catecholamines (NE mainly) in the cytosol
Dopamine Re-Uptake
#2 - VMAT
VMAT = vesicular monoamine transport
transports ALL monoamines into vesicles for release
--> dopamine
--> serotonin 5 - HT
--> NE = Norepinephrine
#1 - DAT
DAT = dopamine transporter
transports Dopamine
directly
back into the dopaminergic neuron
--> NO re-uptake intervention by glial cells like in Glutamate
Recreational Drugs
Dopamine Receptors
G protein coupled receptors
allow in ALL cations?
*Serotonin = 5 HT
(5 hydroxytriptamine)
Recreational Drugs
increased 5-HT release
-->
MDMA
= 3,4-methylenedioxy-methamphetamine = ecstasy
-->
cocaine
(dopamine also)
-->
Amphetamines
(dopamine also)
LSD
--> 5 HT = serotonin agonist
Serotonin-Reuptake
SIMPLE 2 step process
#2 - VMAT
VMAT = vesicular monoamine transport
transports ALL monoamines into vesicles for release
#1 - SERT
serotonin transporter
transports serotonin
directly
back into the serotoninergic cell
--> NO re-uptake intervention by glial cells like in Glutamate
Synthesized
made from tryptophan
--> think of Raph the turkey server
--> think also of a Rave where people use ecstasy = MDMA that affects serotonin
--> RAVE = Raphe Nuclei = MDMA serotonin
Function/Pathways
serotonin mainly controls mood
--> reason why MDMA = increases mood and openness
many other unknown functions
Serotonin = think of the turkey server RAPHE (5 HIAA 5s) and the Tyrant DOPES:
"2 Tyrant DOPES at TABLE 4 TRY to TRYP Raphe the TURKEY SERVER while he gives 5 HIAA 5s to each table"
5 HIAA 5s
= 5 HIAA = 5 - hydroxyindoleacetic acid
--> breakdown product of Serotonin
--> serotonin metabolized in the liver into 5 HIAA normally so would be in the liver
--> in Carcinoid Syndrome, mets to liver gives 5-HIAA in the urine insteads
"TABLE 4 "
= tetrahydrobiopterin
--> needed for both major NT monoamines serotonin and dopamine
--> deficiency leads to PKU and tryptophan build up
*Endocannabinoid
System (ECS)
"endo" meaning endogenous
Anandamide
(mimetic = THC)
tetrahydrocannabinol
Functions of Anandamide
Anandamide supresses DA and other NTs to get rid of useless short term memories
Anandamide also used to inhibit some movements to make us feel relaxed and calm
Anandamide broken down very quickly in synaptic cleft
--> reason why anandamide doesn't give a high, but THC does
Actions of Anandamide
GABA normally released in CNS to inhibit DA release
binds to CB1 receptors on Gabanergic neurons
inhibits release of GABA
--> no inhibition of dopamine
Receptor
binds to ONLY CB1 receptors
2-AG = arachadonoylglycerol
(mimetic = CBD = cannabidiol)
Receptor
binds to both CB1 and CB2 receptors
Actions
regulation of appetite
regulation of immune system functions and
regulation of pain management
CB1 and CB2 receptors
GPC Gs Receptors
work against the TRPV1 receptor shown here in spinal cord neuropathic pain
http://annalsofneurosciences.org/journal/index.php/annal/article/view/374/1252
NT Size Comparison and Synthesis
Peptide NTs
endogenous opioids
--> enkephalin
--> endorphins
since peptides they are made in the soma and transported to the terminal through axon by
FAST
axon transport on microtubules
dense large vesicles
require high frequency APs and diffuse Ca2+ for release
neuropeptides ONLY bind to GPC Receptors
are too big to be re-uptaken by proteins
--> either broken down through enzymatic degredation
--> diffusion
Non-peptide NTs
made mostly in the terminal of the presynaptic neuron or
--> also made in the soma, but then transported to terminal by
SLOW
axonal transport
small and cleear vesicles
require ONLY a single AP or low frequency signal for vesicle release
are more variable in receptors and re-uptake or cycling
--> can bind to both GPC Receptors = metabotropic and ion channels = ionotropic
--> have specialized protein carriers for each NT, can be degraded or they can diffuse
Medium Size = Monoamine NTs and Purines
Monoamines made from tyrosine and tryptophan
--> think dopamine addictive drugs bout from TYRONE the drug dealer
tyrosine
monoamines
--> L-DOPA (DA precursor)
--> Dopamine (DA)
--> Norepinephrine (NE)
tryptophan
monoamines
--> Serotonin (5 HT hydroxythiamide)
Smallest size = Amino Acid NTs
note both main excitatory and inhibitor NTs are the smallest amino acids
--> Glutamate (Glu)
--> GABA
Synaptic Integration
Glutamatergic (Ionotropic)
receptors
coexistence of NMDA & AMPA
NMDA
coincidence detector
channels open only when presynaptic & postsynaptic cell = active
postsynaptic = depolarized (thanks to AMPA) so Mg2+ block removed from NMDA receptor channel
presynaptic = releasing glutamate
Na+ & Ca2+ enter postsynaptic cell
increased Ca2+ causes cascade of events
affect gene expression
increased synaptic strength for memory & learning
activate enzymes
regulates opening of ion channels
opening = activity dependent
AMPA channels mediate initial depolarization (Na+ & K+)
reason why AMPA & NMDA coexist
both ligand & voltage gated
voltage: at rest Vm channel is blocked by Mg2+
Mg2+ block removed by depolarization
(+) ion repelled by relatively positive charge inside cell
ligand: glutamate must bind
ions
Ca2+
K+
Na+
AMPA
ions
K+
Na+
Kainate
Synaptic Integration
location of inhibitory inputs
presynaptic inhibition
specific – aimed @ particular excitatory inputs
decrease amount of depolarization in terminal
less quanta released
postsynaptic inhibition
affects all inputs
non-specific
shunting inhibition
shunts signal through Cl- channel opening
inhibitory synapse closer to soma than excitatory
causes outward current
subthreshold signal decay w/ distance
synapses add together in 2 ways
temporal summation
one presynaptic cell sends sequential inputs that lead to depolarization to threshold
spatial summation
many inputs from several presynaptic cells lead to depolarization to threshold
integration of (+) & (-) inputs occurs on dendrites & soma
integration = relationship between inputs & outputs
Convergence: most cells receive inputs from several cells
sensory input –> CNS –> motor output
Central synapses
in
CNS
presynaptic neuron is unlikely to excite postsynaptic cell to threshold
EPSP & IPSP work simultaneously on cell
@ NMJ AP in presynaptic cell WILL lead to EPP in muscle cells large enough to reach threshold
Divergence: most cells send inputs to several other neurons
