What are the small molecule NT? *
- amino acids – glutamate, gaba, glycine
- biogenic amines – dopamine, norepinephrine, serontonin
what are the amiunoacid NT?
gaba, gluamate, glycine
what are the biogenic amine NT?
dopamine, norepinephrine, serotonin
how many different neuropeptides are there
more than 100 different peptides
neuropeptides are typically ___ amino acids long
what are the two major classes of NT?
small moelcule and neuropetides
The concentration of neurotransmitter within the synaptic cleft is tightly controlled via regulation of:
synthesis, packaging, release, and removal
where are small moelcule NT made?
how are small NT packaged into vesicles?
by specific transport proteins in the vesicle membrane
where are neuropeptide NT made and packaged?
within the cell body
how are vesicles of enruopeptides transported to the nerve terminal?
via fast axonal transport
___ neurotransmitters can respond very rapidly?
are right there in the synaptic terminal to respond quickly
___ neurotransmitter release must be carefully regulated to prevent depletion.
ionotropic receptors are ____ gated ion channels that open in response to ligand bonding
how many subunits do ionotropic chanels contain? how many transmembrane domains does each subunit contain?
5 subunits; 3-4 transmembrane domains
how is diversity established with ionotropic NT?
muleiple subunits are assembled in different orders
metabotropic coupled receptors activate ___ in response to ligand binding
activated G-proteins modulate ion channels either
directly or indirectly
how many transmembrane domains does each monmeric metabotropic receptor have?
7 transmembrane domains
what are the functions of acetylcholine in the CNS?
Attention, arousal, reward plasticity.
Enhances sensory functions upon waking
Damage to cholinergic system is associated with the ___
memory defecits in AD
where is acetylcholien found in the peripheral NS?
synapses in ganglia of the visceral motor system
how is AcH synthesized?
enzymatically in nerve terminal from acetyl-CoA and
how is acetylcholine removed from the synaptic cleft?
via cleavage to acetate and choline by acetylcholinesterase
after degradation, how is more acetylcholine made?
choline is taken up by nerve terminal via a specific transporter and is used to synthesize more Ach
how are Organophosphates such as some insecticides and nerve gas hamrful to humans?
inhibit acetylcholinesterase causing ACh to accumulate at cholinergic synapses.
what is the result of organophasopates (nerve gases and insectisides) causing acetylcholine build up at the NMJ?
causes muscle paralysis
___ ach receptors mediate most acetylcholine effects in the brain?
scopolamine and atropine are
metabotropic achetylcholine anatagonists
what are the symptoms of myasthenia gravis?
with myasthenia gravis, patients have antibodies against
nicotinic acetylcholien receptors
how is the structure of the NMJ altered in myasthenia gravis
- dec concentration of acetylcholine receptors in postsynpatic membrane
- sparse and shallow junctional folds
- expanded synaptic cleft
size of ___ and ___ is reduced with myasthenia gravis
mini endplate potentials and endplate potentials
with myasthenai gravis, what is different during repeated stimualtion
the compound AP will be decreased in size (fatigue)
the probability of what is reduced with myasthenia gravis?
that a presynaptic AP will elicit a postsynatpci actioin potential
what does the tx of mysathenia gravis include?
____ is the most prominent NT for normal brain function
(more than half of all brain synapses use glutamate)
____ has been shown to slowglutamate reuptake –> raising potential for neuroexoticity
why is glutamine important?
glutamate cannot cross blood brain barrier, but glutamine can
how and where is gltuamate synthesized?
in the nerve terminal from
- the transamination of a-ketoglutarate
how is glutamate removed from the synaptic cleft?
by high affinity glutamate transporters on both the nerve terminal and nearby glial cells
what do glial cells do with gltuamate sucked up from the synaptic cleft?
glutamate is converted into glutamine and then transported out of the cell and back into nerve terminals
___ binding is required to open NMDA channel
__ ions can pass through NMDA channels
Gaba is widely used where
- in the brain – 1/3 of all brain synapses use gaba
- in local interneurons and purkinje cells of cerebellum
where is glyceine mostly used?
in the synapses in the spinal cord
how is gaba synthesize?
in nerve terminals from glutamate
what is needed for gaba to be made from glutamate?
pyridoxal phosphate (PLP) derived from vitamin B6
how is gaba removed from the synaptic cleft?
by specific transporters on nerve terminals and nearby glia
decreased gaba function can cause
how is glyceine synthesized?
in nerve terminals from serine
how is glycine removed from the synaptic cleft
by specific transporters on nerve terminals and nearby glia
how can there be excess glycine? what can thise cause
defects in the glycine transporter can cause excessive glycine
excess glycine –> neonatal disease characterized by lethargy and mental retardation
strychnine is a
glyceine receptor anatognist
what are the effects of strychine
blocks gaba ionotropic receptors –> leads to overacitity int he spinal cord and brainstem –> seizures
where are the biogenic amines made
in nerve terminals
what packages the biogenic amines
vesicualr monoamine transporter (VMAT)
how are the biogenic amines removed from the synaptic cleft
reuptake into nerve terminals
what types of receptors do the biogenic amines ahve?
- have metabotropic
- serotonin has ionotropic as well
how is dopamine made?
tyrospine –> dopa —> dopamine
how is norepinephrine made?
tyrospine –> dopa —> dopamine –> norepinephrine
how is epinephtrine made?
tyrospine –> dopa —> dopamine –> norepinephrine –> epinpeinphrine
80% of brain dopamine found in ___
corpus striatum (which receives major input from the substantia nigra)
midbrain dopamine system projections from the
ventral tegmental area to ventral parts of the striatum
what is the midbrain dopamien system invovled in
motivation, reward, reinforcement
what are doipamine projections tot he cortex involved in
norepinephrine neurons from the locus coerelus project to
forebriana nd brainstem targets
what is the major transmitter of the sympathetic motor system
catehcolimine receptors are all
anatagonists of ___ receptors in the medulla are sued as antiemtics
dopamine receptors act by
activiating or inhbiitng adenyl cyclase
dopamine blocks dopamine transports causing
a net increase in release of doapmine
ampohetamine inhbiits both dopamine and norepeinphrine causing a
net increase in release of dopamine and norepinephrine
raphe nuclei in the upper brainstem project to
forebrain and also to the brainstem
how is serotonin transported back into the nerve terminal
by specific serotonin transporter or (SERT)
metabotropic recpeotrs of serotonin are involved in
emotions, circadian rhtyms, motor behaviors, mental arousal
activation of ___ mediates satiety and decreased food consumption
metabotropic serotonergic receptors
MAO inhbiitors block the breakdown of
tricyclic antidperessants block the reuptake of
norepeinhprine and serotonin
peptide NT are implicated in modulating
emotions, perceptions of pain, and repsonses to stress
how are neuropeptides made?
synthesized as pre-propetides in the er in the cell body
what are peptide nt sometimes co released with
small molecule NT
how are neuropeptides degraded in the synaptic cleft
- removed by peptidases which degrade them
- degraded to more activ epeptides by endopeptidases
metabotropic receptors of peptide NT are activated at ___ peptide concnetrations
morphine binds to the same receptors are
which NT have just iontropic receptors
what are the main functions of dopamine
coordiantion of body movement, movtivation, reward reinforcement
what can cause a neonatal disease characterized by lethargy and mental retardation?