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Chemical vs Electrical Synapse |
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Fast vs slow transmission |
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Chemical synpase in the CNS
(compared to the simplicity of the NMJ) |
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Multiple endings, multiple receptors, multiple transmitters, summation of action.
where? |
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Definition
Chemical synpase in the CNS |
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Practical side of studying CNS synpase |
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challenge in studying synaptic transmission in the cns |
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Definition
not understandind the mechanism. probably won't |
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nature's choice to make a receptor |
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Definition
high for its ligand
affinity is defined by Kd - equilibrium dissociation constant
the smaller the Kd the higher the affinity
Kd is the concentration of the ligand [L/H] when 50% of the receptor is occupied by that ligand |
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Definition
how selective is the binding
imporant to reduce side effects
ligand specificity - receptors require certain ligands for binding
tissue or cellular specificity ( where receptor can be found)
temporal specifcity (when the receptor is being exposed) |
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neurochemistry of the cholinergic synapse |
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rate limiting step of nAChR
(choline uptake) |
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Definition
mAchr bind to it
toxcin from certain mushroom
first excites then blocks the receptor
antagonists - atropine & scopolamine
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muscarine - tissue distribution |
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Definition
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Term
cholingeric neruons & diseases |
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Definition
implicated in:
alzheimers
huntingtons
learning/ memory
cognition/pain |
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Term
what we know about mAchr/ what we do not know |
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Definition
"Knowing the messenger is fine we know that ACH binds to mAchr but it doesn't tell us anything about the message" |
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previously thought - GABA |
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Definition
previously thought that GABA is the major inhibitory trasnmitter in the forebrain; the major inhibitory transmitter in the brain stem and spinal cord in glycine. |
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molecular mechanisms of GABAergic synpases |
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GABA receptor
A* & C - retina |
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GABAb receptor - increase K+ conductance to induce hyperpolarization |
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Definition
this channel/receptor is a cl- channel and induces IPSP
increased Cl- permeability Ecl is a -70 mV at this membrane potential, Cl- would go into the cell
hyperpolarization
decreased effectiveness of excitatory input |
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Term
GABA a receptoris modulated by 2 classes of drugs |
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Definition
benzodiazepines - increase the frequency of cl- channel opening
barbiturates - increase duration of cl- channel opening slightly decrease the frequency of opening |
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GABAa receptor and drug discovery |
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Definition
to make drugs better than BDZS & barbiturates to develop drugs that have anxiolytic and anti convulsant actions but no sedative and muscle relaxant actions for mental disease or epileptic patients |
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Gaba a receptor and anesthesia |
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Definition
this emergin hypothesis proposes anesthesia work via GABAa receptor. introducting point mutation to modigy GABA a receptor gene can make the receptor unresponsive to anesthestics |
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why are we interested in monoamines? |
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NE Neurons in the CNS
Disclaimer |
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Definition
do not confuse CNS NE/E neurons with the sympathetic ganglia.
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How many major sources for NE neurons in the CNS? |
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Regulation of biosynthesis and release of NE |
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Regulation of biosynethic pathway |
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step 1 - 10 biosynthetic pathway |
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Definition
response wabes in time despite the continued presenc of a stimulus at constant intensity |
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heterologous densitization |
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homologous desensitization |
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Definition
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down-regulation of receptor gene expression |
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Definition
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sequestering of receptor away from cell membrane into a poorly defined vesicle |
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Definition
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receptor phsophorylation
( beta adrenergic receptors) |
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Definition
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2 monoaminergic transmitters |
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Definition
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How may DA systems in the CNS |
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Definition
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DA is a transmitter
(historical review) |
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central DA systemvs NE System |
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3 DA systems
intermediate? |
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Definition
DA in the hypthalamus
DA as a PRL inhibitor
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Definition
major neuroendocrine related cause of reproductive disturbance in both men and women. the treatment of hyperprolactinemia has greatly benefited from the generation of progressively more effective and selective dopaminergic drugs |
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Definition
midbrain --> nigrostriatal projection, mesocrotical projection, mesolimbic projection |
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Definition
substanatia niagra (midbrain) --> neo(striatum) caudate + putamen
this is the pojection implicated in PD |
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Definition
midbrain --> cortex
SNc & VTA (midbrain DA neurons)-->limbic cortex |
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Definition
mibrain Da neurons --> other limbic structures |
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emotional reward system
(DA) system |
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Definition
Parkinsons Disease
Primarily a DA-deficiency state resulting from degeneration or injury to DA neurons
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Definition
It has been used to treat the symptom of PD for over 30 years now. However, there is still a great deal of controversy over its place in treatment |
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DA nerve terminal transporters |
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DA nerve terminal receptors |
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Da transporters - 2 types |
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DAT as brains principal
"cocaine receptor" |
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Definition
scientists hope to develop a drug that can block the DA binding site yet preserve the reuptake site for DA |
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DA receptors (all 7 TMDs) |
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Definition
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Definition
5 have been cloned D1-D5
overlap in distribution
two groups D1/D5 & D2/D3/D4
the two groups operate through opposite pathways yet achieve synergistic effect |
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Serotonin as a neurotransmitter
synthesis |
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Definition
tryptophan (plasma) active uptake--> tryptophan (neuron) tryptophan hydroxylase (rate limiting step) --> 5-OH trypto decarboxylase (same as the one in the NE pathway) --> 5-hdroxy tryptamine (5-HT) |
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Seratonin as a neurotransmitter
Reuptake |
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Definition
transporter belongs to the DAT, NET family
12 TMD
NA+ economy
blocked by drugs such as Fluxetine (Prozax) |
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5-HT & hallucinogenic drugs LSD |
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as an example to dscuss the problem in psychopharmacology |
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what purpose does glutamate serve |
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Definition
major excitatory transmitter in the brain |
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Definition
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glutamate
establising as a transmitter |
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Definition
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glutamate
distribution of glutamatergic neurons in the CNS |
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Definition
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glutamate
biosynthesis of glutamate as a transmitter |
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glutamate receptor
ionotropic receptors |
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ionotropic receptors
the classification |
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ionotropic receptors
how do they operate |
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ionotropic receptors
the multiple binding site of NMDA receptors |
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metabotropic glutamate receptor |
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glutamate reverse transport mechanism |
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Definition
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glutamate apoptosis and necrosis |
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retrograde messengers - parasynaptic transmission |
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Peptidergic regulation of pair bonding |
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