Term
| Resting membrane potential |
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Definition
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Term
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Definition
| activation of sensory neurons by external stimuli -> action potentials |
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Term
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Definition
| activation allows transmission of info from one neuron to another -> action potential |
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Term
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Definition
| electrical signals from receptor/synaptic potentials... spikes, impulses |
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Term
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Definition
| current makes the membrane potential more negative. nothing happens |
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Term
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Definition
| current of opposite polarity delivered. membrane becomes more positive than resting potential... at a certain point (threshold) |
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Term
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Definition
| certain level of membrane potential where action potential occurs |
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Term
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Definition
| when only small depolarizing currents or hyperpolarizing current pulses go through. no action potential is created |
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Term
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Definition
| actively move ions into or out of cells against concentration gradients. ion concentration gradients are established by these |
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Term
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Definition
| allow only certain kinds of ions to cross the membrane in direction of their conc gradients. selective permeability is due to these |
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Term
| electrochemical equilibrium |
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Definition
| exact balance between two opposing forces: conc gradient that causes K to move and opposing electrical gradient that tends to stop K from moving across the mmbrane |
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Term
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Definition
E = (58/z) * log out/in
10/100 -> -58 mV (K) 58 (Na) |
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Term
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Definition
| V = 58log (Pk(Kout) + Pna(Naout) + Pcl(Clout))/(same but inside!) |
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Term
| Resting membrane Na, K, Cl, and Ca concentrations |
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Definition
(in/out)
Na = 5/140
K = 140/5
Cl = 100/500
Ca = 0.0001/10 |
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Term
| Why -60mV resting potential? |
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Definition
| Because of potassium is higher on the inside than out and it wants to flow outward -> negative potential. dependent on K because membrane is only permeable to K at resting... K leak channels |
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Term
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Definition
| generated across the membrane at electrochemical equilibrium |
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Term
| Phases of an action potential |
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Definition
| rising, overshoot, falling, undershoot |
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Term
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Definition
| membrane becomes extraordinarily permeable to Na and it rushes in... making the membrane really positive. caused by opening of Na selective channels that are closed at resting state |
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Term
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Definition
| when the action potential becomes the most positive and Na permeability is much greater than potassium |
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Term
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Definition
| sodium channels close and the membrane potential falls. primarily permeable to K and is more permeable. rapidly repolarizes. membrane hyperpolarizes because K permeability becomes even greater than at res |
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Term
| What determines the voltage? |
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Definition
| Both Na and K are 10 fold altered in concentration--but there's selective leakage of K at resting potential and Na during action potential determines it |
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Term
| Current/voltage clamp method |
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Definition
| controls/clamps membrane potential/voltage at any level desired by experimenter. measures membrane potential w/ microelectrode placed in cell and electronically compares this voltage to the voltage maintained (command voltage). clamp passes current back into the cell through another intracellular electrode. this feedback circuit holds membrane potential at desired level. current needed to maintain voltage equals current flowing out of membrane |
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Term
| Two voltage dependent ion currents |
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Definition
| Early current caused by Na (flow in occurs if potential less positive than Ena and reverses when more positive). late current is a delayed efflux of K producing a sustained otward current |
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Term
| Sodium and potassium blocks |
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Definition
| Tetrodotoxin (TTX) blcoks Na current. Tetraethylammonium ions block K currents |
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Term
| Upon depolarization... conductances |
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Definition
| Fast sodium conductance initially and then slower potassium conductance. K takes longer to activate but depolarization causes Na to decrease and inactivate. K does not inactivate. voltage dependent conductances |
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Term
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Definition
| closely related to membrane permeability and ionic currents change due to this |
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Term
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Definition
| following action potential, axon experiences brief refractory during which it is resistant to further excitation |
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Term
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Definition
| the measurable rate of transmission of an action potential |
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Term
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Definition
| myelination of axons allows ions to flow down axon without leaking out and generate action potentials more effectively at the breaks in myelination (nodes). AP jumps from node to node |
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Term
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Definition
| passive current flow that occurs in the absence of an action potential. current pulse is not strong enough to depolarize and hit the threshold of the membrane |
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Term
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Definition
| glial cells in the CNS that maintain chemical environment |
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Term
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Definition
| glial cells in the CNS that produce myelin for the axons |
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Term
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Definition
| glial cells in the PNS that wrap axons in myelin |
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Term
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Definition
| unmyelinated points on axon where action potentials are generated. sodium channels are only found at these nodes |
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Term
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Definition
| disease of CNS resulting from multiple regions of demyelination & inflammation along axonal pathways. signs&symptoms depend on location of affected regions. compromises action potential conductance |
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Term
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Definition
| have a very high resistance seal as opposed to sharp electrode. allows you to see microscopic currents (single channels. macro is for many channels in one region) and the resultant opening/membrane potential plot |
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Term
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Definition
cell attached = record on the membrane w/ tight contact
whole-cell = membrane break and cytoplasm is same with pipette interior
inside-out = break off piece of membrane with channel on. "air" is cytoplasm domain
outside-out break from both sides of membrane and ends anneal... pipette is inside cell, cytoplasm |
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Term
| States of voltage-gated K & Na channels |
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Definition
closed -> open -> inactivated
both are closed when hyperpolarized. potential depolarized both open (na first) and then na inactivates during depolarization but k does not |
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Term
| heterologous expression of ion channels |
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Definition
| one of the primary tools for studying ion channel function. after id-ing and cloning channel, insert cDNA or RNA into a cell and can study it |
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Term
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Definition
selectively permeable to each of the major physiological ions. Na, Ca, K, Cl
Human genes... 10 Na, 10 Ca, 100 K+, ~5 Cl.
K is the most diverse |
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Term
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Definition
| extracellular activated neurotransmitter receptor (Glutamate), activated by intracellular second messengers: calcium-activated K channel, cyclic (cAMP) gated channel |
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Term
| Stretch and heat activated channels |
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Definition
| respond to heat/membrane deformation. ex. TRP receptors |
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Term
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Definition
two membrane-spanning domains of all ion channels form a central pore through which ions can diffuse... one of them contains a protein loop conferring ion selectivity
AA composition of pore loop differs according to which ion the channel conducts
has to fit the ion when it is dehydrated through the middle (where selectivity comes into play) |
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Term
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Definition
| alpha-4 and beta subunits. |
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Term
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Definition
| several genetic diseases resulting from small but critical alterations in ion channel genes. in most... produce either myotonia (stiffness) or paralysis |
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Term
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Definition
| in charge of generating and maintaining ionic conc gradients for particular ions. allow ions to travel against conc gradients |
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Term
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Definition
| active transporters that acquire energy directly from hydrolysis of ATP |
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Term
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Definition
| responsible for maintaining conc of Na and K. electrogenic=establishes electrochemical gradient because unevenly distributes... 3 Na removed = 2 K in. uses up 1/3 of brains energy |
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Term
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Definition
| takes ions up gradient while taking another ion down its gradient. Na/H regulates intracellular pH |
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Term
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Definition
| transmitter pumps: SerT. transports ions and molecules, one down and the other up the gradient either in same direction (symporter) or in different directions (antiporter) |
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Term
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Definition
| 100 billion neurons in the brain; 1000 synapses each; 100 neurotransmitters |
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Term
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Definition
| permitting direct, passive flow of electrical current from one neuron to another. gap junctions where ions flow through. direct contact! connexins. bi-directional |
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Term
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Definition
| space between neurons = synaptic cleft. synaptic vesicles from presynaptic fuse with membrane and release neurotransmitters that bind to receptors on postsynaptic |
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Term
| electrical synapse in detail |
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Definition
| 3.5 nm gap. 0.1 ms delay. connexins that span both membranes connecting the two. tight junctions. bi directional. used in escape circuits for fast transmittion. synchrony, coordinates chemical signals too |
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Term
| chemical synapse in detail |
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Definition
| synaptic vesicles fuse and release neurotransmitter when calcium flows in. synaptic cleft where it goes through. cotransmitters (two in same terminal), 3-5ms delay |
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Term
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Definition
| vesicle components transported by slow axonal transport down to terminal to synthesize transmitters ~1mm/day |
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Term
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Definition
| made in the synapse and packaged in 50 nm small clear core fesicles. fast release |
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Term
| peptides (as neurotransmitters) |
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Definition
| made in cell body and travel by fast axonal transport ~400 mm/day along microtubules. packaged in >100nm large dense-core vesicles. slower release and needs more Ca to rush in |
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Term
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Definition
| examined at NMJ. miniature end plate potentials (MEPPs- occur in absence of stimulation). each MEPP corresponds to a number of vesicles (quanta) and many MEPPS add up to an EPP. |
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Term
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Definition
| synapses of spinal motor neuron and skeletal muscle cells |
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Term
| end plate potential (EPP) |
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Definition
| when membrane potential in postsynaptic muscle fiber is large enough to induce action potential |
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Term
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Definition
| one minute. fusion takes 1ms, endocytosis takes 15s and fusion-dock-priming takes 45s. refer to pg. 97 figure 5.9 |
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Term
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Definition
| synapsin (binds to synaptic vesicles) and may cross-link vesicles to actin filaments in cytoskeleton, keeping them tethered. mobilization of this pool results from phosphorylation of synapsin by kinases... Ca/calmodulin-dependent protein kinase type II (CaMKII). syanpsin dissociates and vesicles are free to go to plasma membrane... dock and then fuse |
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Term
| myasthenias; botilism and tetanus; latrotoxin |
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Definition
| abnormal transmission at neuromuscular synapses that leaad to mucular weakness and fatigueability and due to reduction in neurotransmitter release because of loss of Ca channels. toxins, botulinum and tetanus toxin mess up the docking. latrotoxin causes massive discharge of synaptic vesicles even when Ca is absent |
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Term
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Definition
| neurexins bind to synaptotagmin (important for exocytosis) in presynaptic--specify synapse formations. neroligins mediate synapse formatioins on the postsynaptic. disorders can arise like autism and schizo. neurexin is like a receptor for neroligin and the two contact and "shake hands" making a connection between the two and produce a synapse |
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Term
| neurotransmitter receptors |
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Definition
| either ionotropic or metabotropic. |
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Term
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Definition
| linked directly to ion channels (aka ligand-gated ion channels). combine transmitter binding and channel functions into one. for small molecule usually and fast! |
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Term
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Definition
| eventual movement of ions through a channel depends on one or more metabolic steps. usually require G-proteins. also called G-protein-coupled receptors |
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Term
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Definition
| the macroscopic current resulting from summed oepning of many channels at the end plate |
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Term
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Definition
| excitatory post synaptic potentials increase likelihood of action potentials occuring |
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Term
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Definition
| inhibitory post synaptic potentials decrease likelihood of action potentials from occuring |
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Term
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Definition
| allows subthreshold epsps to incluence action potential production. they sum together (in space and time) to go above threshold and cause membrane to depolarize |
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Term
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Definition
| relatively large transmitter molecules composed of 3 to 36 amino acids |
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Term
| small-molecule neurotransmitters |
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Definition
| individual amino acids, ions, etc. much smaller than neuropeptides. biogenic amines (dopa, nore, epi, seroto, hista) are often discussed separately |
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Term
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Definition
| nACh (nACh-alpha), AMPA (gluA1), NMDA (GluN), Kainate (GluK), GABA (GABA-A), Serotonin (5HT3), purinergic (p2x), glycine |
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Term
| metabotropic receptors (8) |
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Definition
| ACh (muscarinic M1), glutamate (mGlu), GABA (GABA-B), dopamine (D1), serotonin (5HT1), Adrenergic (beta), histamine (H), purine (A&P class) |
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Term
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Definition
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Term
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Definition
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Term
| ACh rate-limiting step in synthesis |
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
| glutamate rate-limiting step in synthesis |
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Definition
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Term
| glutamate removal mechanism |
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
| catecholamines (epi, nore, dopa) effect |
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Definition
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Term
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Definition
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Term
| catecholamine rate-lim step |
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Definition
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Term
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Definition
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Term
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Definition
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Term
| serotonin (5-HT) precursor |
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Definition
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Term
| serotonin (5-HT) rate-lim step |
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
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Term
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Definition
| mitochondrial oxidative phosphorylation; glycolysis |
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Term
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Definition
| hydrolysis to AMP and adenosine |
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Term
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Definition
| excitatory and inhibitory |
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Term
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Definition
| amino acids, protein synthesis |
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Term
| neuropeptides rate-lim step |
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Definition
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Term
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Definition
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Term
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Definition
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Term
| endocannabinoids precursor |
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Definition
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Term
| endocannabinoids rate-lim step |
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Definition
| enzymatic modification of lipids |
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Term
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Definition
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Term
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Definition
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Term
Acetylcholine (ACh)
removal, transporters, toxin |
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Definition
| acetylcholinesterase (AChE) hydrolyzes ACh -> acetate and choline in the synapse. Na+/choline transporter takes choline back into presynaptic terminal. Vesicle H+ exchange transporter. organophosphates (sarin) inhibit AChE causing depolarization -> neuromuscular paralysis. |
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Term
| nicotinic ACh receptor (nAChR) |
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Definition
| mediates postsynaptic acitions. ionotropic. five subunits. a-bungarotoxin, curare = blocks nAChR. nicotine, betel nut = binds to it and stimulates |
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Term
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Definition
| does not cross BBB. synthesized in cytoplasm and packaged into vesicles = VGLUT. requires depolarization and transmits Ca (NMDA) |
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Term
| Glutamate-glia-glutamine cycle |
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Definition
| EAATs (excitatory amino acid transporters) take up glutamate into glial cells. converted into glutamine by glutamine synthetase then transported out and into nerve terminals |
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Term
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Definition
| NMDA, AMPA, and kainate. ionotropic. always produce EPSPs (Na, K, Ca) |
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Term
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Definition
| when receptors get overactivated due to excess glutamate and results in nerve cell damage or death |
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Term
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Definition
| Ca can come in. Mg blocks this pore at hyperpolarized & resting states, depolarization -> pushes ion out. SLOWer and longer lasting |
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Term
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Definition
| main transmission of glutamate. faster than NMDA |
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Term
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Definition
| weaker. sometimes found on presynaptic as feedback to regulate glutamate release |
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Term
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Definition
| inhibitory. GAT = high-affinity transporters on glia and neurons to remove. |
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Term
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Definition
GABA-A, GABA-B, GABA-C (A and C are ionotropic, B is metabotropic). inhibitory because they're permeable to Cl- (A&C). 5 subunits. for B, inhibitory because it activates K channels and blocking Ca channels = hyperpolarization. heterodimers
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Term
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Definition
| benzodiazepines and barbiturates-treat epilepsy, sedation, anesthesia. binding site in pore domain |
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Term
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Definition
| three catecholamines = dopamine, norepinephrine, and epinephrine. and histamine & serotonin. |
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Term
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Definition
| tyrosine -> dopamine -> noradrenaline (norepinephrine) -> adrenaline (epinephrine) |
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Term
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Definition
| coordination of body movements. motivation, reward, reinforcement. loaded into synaptic vesicles via VMAT. acts on GPCRs. activate/inhibit AC. in substantia nigra |
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Term
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Definition
| vesicular monoamine transporter. blocked by reserpine |
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Term
| norepinephrine (noradrenaline) |
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Definition
| sleep, wakefulness, attention, feeding. in locus coeruleus. acts on a and b-adrenergic receptors (GPCR) |
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Term
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Definition
| Na-dependent dopamine transporter. reuptake of dopamine into nerve terminals/surrounding glial ells. cocaine inhibits DAT |
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Term
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Definition
| monoamine oxidase and catechol O-methyltransferase. enzymes involved in catabolism of dopamine in neurons & glial cells. (MAO-Inhibitors) |
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Term
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Definition
| primarily in tegmental system and in medulla. VMAT loads. acts on a and b-adrenergic receptors |
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Term
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Definition
| from tyrosine to L-DOPA. precursor to the catecholamines |
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Term
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Definition
| in hypothalamus. metabotropic receptors (like H1 in the CNS). diphenhydramine (benadryl) acts as an antagonist to mediate allergic reactions. degraded by histamine methyltransferase and MAO |
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Term
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Definition
| (5-HT). found in raphe nuclei. SerT transporter terminates serotonin activity. catabolic pathway mediated by MAO |
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Term
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Definition
| selective serotonin reuptake inhibitors. inhibit transport of 5-HT by SERT (Prozac) |
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Term
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Definition
| all are metabotropic except for 5-HT3 |
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Term
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Definition
| P2X and A2A adenosine receptor |
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Term
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Definition
| receptor for ATP. ionotropic |
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Term
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Definition
| adenosine receptor. G-protein coupled receptor -> cAMP. binds adenosine. caffeine blocks adenosine receptors = stimulates |
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Term
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Definition
| hormones or proteins, amino acids (3-36) |
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Term
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Definition
| larger than the mature peptide produced by neuron. processing of them takes place |
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Term
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Definition
| mature polypeptide that then gets packaged into vesicles |
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Term
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Definition
| ex. substance P. sensory neurotransmitter in spinal cord. pain sensing |
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Term
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Definition
| bind to same receptors that opium does. ex. endorphins. act as analgesics |
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Term
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Definition
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Term
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Definition
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Term
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Definition
| ex. neuropeptide Y, blocks traumatic events (used by the army) |
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Term
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Definition
| interact with cannabinoid receptors (targets of weed). produced from degradation of membrane lipids |
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Term
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Definition
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Term
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Definition
| cannabinoid receptor in the CNS. GPCR. |
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Term
| endocannabinoids inhibition |
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Definition
| serve as retrograde signals to regulate GABA release at certain terminals. released after membrane is depolarized with more Ca and binds to CB1 on presynaptic and inhibits GABA released |
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Term
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Definition
| acts over a longer range than synaptic transmission and involves the secretion of chemical signals onto a group of nearby target cells. ex. serotonin |
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Term
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Definition
| special form of chemical signaling that transfers info from one neuron to another ex. ACh |
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Term
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Definition
| secretion of hormones into the bloodstream where they can affect targets throughout the body ex. vasopressin |
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Term
| intracellular signal transduction |
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Definition
| molecular signal and a receptor that transduces the info with a target molecule to mediate the response |
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Term
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Definition
| occurs because individual signaling reactions can generate a much larger number of molecular products than the number of molecules that initiate the reaction. occurs in all signal transduction pathways |
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Term
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Definition
| when neurotransmitter serves as the signal and receptors serve as transducing receptor, and target is an ion channel that is altered to cause electrical response |
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Term
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Definition
| typically bind to receptors associated with cell membranes. ex. neurotransmitters bind to receptors. short-lived because rapidly metabolized/internalized by endocytosis |
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Term
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Definition
| molecules can cross the plasma membrane to act directly on receptors that are inside the cell ex. steroids |
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Term
| cell-associated signaling |
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Definition
| molecules are arrayed on extracellular surface of the plasma membrane. act only on other cells that are physically in contact with the cell that carries such signals |
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Term
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Definition
| aka ligand-gated ion channels/ionotropic receptors. have receptor and transducing functions as part of the same protein molecule. open/close of ion channel pore. can lead to entry of Ca -> second messenger |
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Term
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Definition
| have extracellular binding site. intracellular domain is an enzyme whose catalytic activity is regulated by the binding of the extracellular signal. usually protein kinases that phosphorylate intracellular target proteins/tyrosine residues. ex. TrkA receptor, neurotropin binding |
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Term
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Definition
| g-protein-coupled receptors involve intermediate transducing molecule = GTP-binding proteins/G-proteins. 7-transmembrane receptors (metabotropic). ex. B-adrenergic, muscarinic, etc. |
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Term
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Definition
| activated by cell-permeant/lipophilic signaling molecules. lead to activation of signaling cascades producing new mRNA/protein within target cell. often comprise of receptor protein bound with inhibitory complex |
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Term
| heterotrimeric g-proteins |
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Definition
| composed of 3 distinct subunits. a, b, and y. a binds either GTP or GDP. binding of GDP allows a to bind to b and y = inactive trimer. extracellular signal turns GDP -> GTP and a dissociates and activates the g-protein. |
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Term
monomeric g-proteins
(small g-proteins) |
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Definition
| also relay signals from activated cell surface receptors to intracellular targets like cytoskeleton and vesical trafficking. ex. Ras (helps regulate cell differentiation and proliferation by relaying signals from receptor kinases to nucleus) |
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Term
| 3 different heterotrimeric g-proteins |
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Definition
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Term
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Definition
| ex. b-adrenergic with norepinephrine. synthesis! activates AC -> cAMP -> PKA -> increase protein phorsphorylation |
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Term
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Definition
| activating. ex. mGluR with glutamate. -> phospholipase C -> DAG & IP3 -> Ca release and PKC -> protein phosphorylation & activate Ca-binding proteins |
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Term
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Definition
| inhibitory. ex. dopamine D2 with dopamine. deactivates AC, camp, and PKA. decreases protein phosphorylation |
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Term
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Definition
| info is transmitted by transient rise in cytoplasmic ca conc. ca binds to other proteins ex. calmodulin effects protein kinases. ca level in cell typically low. calcium pump, Na/Ca exchanger = replaces intra Ca with extra Na. calbindin serve as ca buffers. IP3 opens ca channels |
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Term
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Definition
| cyclic adenosine monophosphate. derivative of ATP. produced when AC is activated by G-proteins. can bind to PKA (phosphorylates proteins) and ligand-gated ion channels (neuronal signaling) |
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Term
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Definition
| cyclic guanosine monophosphate. derivative of GTP and produced after GC is activated. can bind to PKG (phosphorylates proteins) and ligand-gated ion channels (neuronal signaling) |
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Term
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Definition
| inositol triphosphate. leaves cell membrane and diffuses within cytosol. binds to IP3 reeptors, channels that release ca from ER. action is to produce another second messenger |
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Term
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Definition
| diacylglycerol. remains within membrane and activates protein kinase C (phosphorylates substrate proteins in plasma membrane and elsewhere) |
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Term
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Definition
| membrane messengers produced from phosphatidylinositol biphosphate (PIP2). cleaved by phospholipase C, activated by G-proteins and calcium ions. split into two smaller molecules... DAG and IP3 |
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Term
| cyclic nucleotides removal |
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Definition
| degraded by phosphodiesterases, enzymes that cleave phosphodiester bonds and convert cAMP and CGMP into AMP and GMP |
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Term
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Definition
| actions are terminated by enzymes that convert them into inert forms and recycled back to produce new PIP2 |
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Term
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Definition
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Term
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Definition
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Term
| protein kinase/phosphatase cycle |
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Definition
| protein kinases phosphorylate. protein phosphatases remove phosphates. typically act either on Ser/Thr resideies, or Tyr. second messenger activates protein kinase and phosphorylates protein. second messenger regulates protein phosphatase which then removes phosphate from protein |
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Term
| cAMP-dependent protein kinase (PKA) |
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Definition
| primary effector of cAMP. tetrameric complex with 2 catalytic and 2 regulatory subunits. cAMP binds and PKA releases catalytic subunits. phosphorylates Ser/Thr residues |
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Term
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Definition
| ca binds to calmodulin and regulates protein phospho/dephosphorylation. CaMKII is most abundant kinase... 14 subunits. activates CaMKII by displacing inhibitory domain from catalytic site |
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Term
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Definition
| diverse monomeric kinases activated by DAG and Ca. DAG causes PKC to move from cytosol to membrane. relieves autoinhibition and causes PKC to phosphorylate various protein substrates. diffuses to cytoskeleton where it phosphorylates other substrate proteins. |
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Term
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Definition
| RTKs = transmembrane proteins that phsophorylate Tyr. Non-receptor tyrosine kinases are cytoplasmic and indirectly activated by extracellular signals. tyrosine phosphorylation is less common than Ser and Thr. important for cell growth and differentiation |
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Term
| mitogen-activated protein kinase (MAPK) |
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Definition
| aka ERKs (extracellular signal-regulated kinases). control of cell growth. activated when phosphorylated by other kinases. part of kinase cascade (typically starts with growth factor) and in turn activates Ras... eventually MAPK gets activated and can phosphorylate transcription factors. |
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Term
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Definition
| Ras activates MAPK by phosphorylation |
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Term
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Definition
| Ca binds to CaMKII and activates it |
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Term
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Definition
| cAMP binds to PKA and its catalytic subunits are freed to phosphorylate target units |
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Term
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Definition
| presence of globular tips/spine heads. synapses innervating dendrites are made from these heads. connected to dendrites by spine necks. site of localized signaling** |
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Term
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Definition
| CREB = cAMP response element binding protein. transcriptional activator. PKA&ras can phosphorylate CREB. can also be phosphorylated by increased ca levels, caused by Ca/calmodulin kinase IV (relative of CamKII)**. genes sensitive to CREB = c-fos, neurotrophin BDNF, tyrosine hydroxylase, etc. |
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Term
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Definition
| can be activated by cAMP/PKA, Ca/CamKIV, and ras/MAPK |
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Term
| nerve growth factor (NGF) |
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Definition
| member of the neurotrophin growth factor family and is required for the differentiation, survival, and synaptic connectivity of sympathetic and sensory neurons. works by binding to a high affinity tyrosine kinase receptor, TrkA found on plasma membrane of target cells. |
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Term
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Definition
| NGF binds to TrkA receptors causing them to dimerize. then phosphorylates its partner receptor and triggers three different pathways |
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Term
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Definition
| PI3/Akt pathway, ras/MAPK, and PLC/Ca pathway |
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Term
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Definition
| TrkA activates this pathway... adapter proteins -> PI 3 kinase -> Akt kinase which increases cell survival, inhibits cell death |
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Term
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Definition
| TrkA triggers ras cascade. GEF -> ras -> kinases activated -> MAPK -> neurite outgrowth and neuronal differentiation |
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Term
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Definition
| TrkA stimulates activity of phospholipase C which increases IP3 and DAG and increases Ca release from ER and activates PKC -> neurite outgrowth and neuronal differentiation |
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Term
| long-term depression (LTD) |
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Definition
| observed between synapses of parallel fibers (PFs) and their Purkinje cell targets. form of synaptic plasticity that causes PF synapses to become less effective |
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Term
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Definition
| Pfs active... release glutamate activating AMPA and causes small EPSP... PF synaptic transmission generates two second messengers. mGluR/PLC and PKC |
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Term
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Definition
| glutamate released by PFs activates metabotropic glutamate receptors... stimulated phospholipase C and produces IP3 & DAG. |
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Term
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Definition
| LTD is induced when PF synapses are activated at the same time as glutamatergic climbing fiber synapses that also innervate Purkinje cells (produce large EPSPs) causing Ca to enter Purkinje cell. When both synapses are activated. rise in Ca caused by climbing fiber enhances sensitivity of IP3 receptors to IP3 produced by PF and allows IP3 receptors to open and release Ca from ER. large rise in Ca with DAG produced activates PKC. phosphorylates substrate proteins... ultimately changes AMPA receptors at PF synapse so taht these receptors produce smaller electrical signals in response to glutamate released. weakening of synapse = LTD. |
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Term
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Definition
| governs synthesis of catecholamine neurotransmitters (dopamine, norepinephrine, and epinephrine). NGF, electrical activity, and other signals can increase rate of catecholamine synthesis by increasing activity of tyrosine hydroxylase. due to phosphorylation of this enzyme |
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Term
| Tyrosine hydroxylase/protein Ca |
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Definition
| tyrosine hydroxylase is substrate for several protein kinases (PKA, CaMKII, MAPK, and PKC). phosphorylation increases catalytic activity. stimuli elvating cAMP, Ca, and DAG all increase its activity -> increase in rate of catecholamine biosynthesis |
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Term
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Definition
| synaptic facilitation, synaptic depression, synaptic potentiation/augmentation |
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Term
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Definition
| rapid increase in synaptic strength that occurs when two or more action potentials invade presynaptic within few ms of each other. lasts for tens of ms. result of prolonged elevation of presynaptic calcium levels following synaptic activity (mechanisms returning ca to resting levels are much slower). ca builds up and more neurotransmitter is released |
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Term
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Definition
| causes neurotransmitter release to decline during sustained synaptic activity. depression is related to rate of release of vesicles. when rapid, lots of depression and if rate is reduced, less depression. |
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Term
| vesicle depletion hypothesis |
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Definition
| depression causes the strength of transmission to decline until synaptic vesicle supply is replenished |
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Term
| synaptic potentiation & augmentation |
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Definition
| elicited by repeated synaptic activity and serve to increase the amount of transmitter released from presynaptic terminals. enhance ability of incoming ca to trigger fusion of vesicles w/ plasma membrane. augmentation rises and falls over a few seconds, potentiation occurs over tens of seconds to minutes. |
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Term
| post-tetanic potentiation (PTP) |
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Definition
| potentiation (because of slower time course) can greatly outlast the tetanus. |
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Term
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Definition
| sea slug with large neurons. exhibit forms of behavioral plasticity = habituation and sensitization |
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Term
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Definition
| process that causes animal to become less responsive to repeated occurrences of a stimulus ex. siphon stimulation in aplysia, after repeats, withdrawal weakens |
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Term
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Definition
| allows an animal to generalize an aversive response elicited by a noxious stimulus to a variety of other, non-noxious stimuli ex. aplysia habituated to siphon touching... sensitization elicited by pairing with electrical stimulus to tail |
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Term
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Definition
| one sensory-motor, and modulatory |
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Term
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Definition
| Siphon touching activates sensory neuron that excites interneuron and gill motor neuron yielding contraction of gill muscle. shock to animal's tail stimulates modulatory neurons that alter synaptic transmission between siphon sensory neurons and gill motor neurons = sensitization |
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Term
| Facilatory interneuron in aplysia circuit (short term) |
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Definition
| sensory neurons of tail excite modulatory interneurons that release serotonin on presynaptic terminals of sensory neurons of siphon... enhances transmitter release from siphon neuron terminals -> increased synaptic excitation of the motor neurons. serotonin released binds to GPCRs on presynaptic terminals of siphon... stimulating cAMP and binds to PKA -> reduce probability of K channels opening... prolongs action potential -> more Ca influx |
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Term
| long-term sensitization in aplysia |
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Definition
| same serotonin-induced enhancement of glutamate release... but due to changes in gene expression and protein synthesis = long. with repeated training... serotonin-activated PKA now phosphorylates and activates CREB, increasing trasncription of genes. CREB stimulates ubiquitin hydroxylase (stimulates degradation of reg subunit of PKA) = PKA always active and no longer requires serotonin. CREB stimulates C/EBP stimulates transcription of genes that cause addition of synaptic terminals -> long term increase in number of synapses between sensory and motor neurons |
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Term
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Definition
| rutabaga (mutant adenylyl cyclase-converts ATP to cAMP) and dunce (mutant phosphodiesterase-degrades cAMP). mutants showed lowered performance in learning and memory |
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Term
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Definition
| brain area that is esp important in formation and/or retrieval of some forms of memory. 5'-12 hrs*** |
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Term
| long-term potentiation (LTP) |
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Definition
| patterns of synaptic activity producing long-lasting increase in synaptic strength |
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Term
long-term depression (LTD)
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Definition
| patterns of activity produce a long-lasting decrease in synaptic strength |
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Term
| Sites of LTP in Hippocampus |
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Definition
| perforant pathway (from entorhinal cortex) -> Mossy fibers (granule cell) -> CA3 pyramidal cell -> goes through schaffer collaterals -> CA1 pyramidal cell. Refer to pg. 187, figure 8.6 |
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Term
| Schaffer collatarels/CA3-CA1 |
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Definition
| CA1 region forms thick band (stratum radiatum). receives synapses from Schaffer collatorals... axons of pyramidal cells in CA3 region. LTP is observed from high-frequency train stimuli from Schaffer collatarels to CA1 |
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Term
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Definition
| LTP is state-dependent = state of membrane potential of postsynaptic cell determines whether or not LTP occurs. If single weak stimulus to Schaffercollaterals is paired with strong depolarization of CA1 cell, activated schaffer collateral synapses undergo LTP (only if tightly linked in time) |
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Term
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Definition
| LTP induced by activation of one synapse does not occur in other, inactive synapses that contact same neuron. Restricted to activated synapses |
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Term
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Definition
| pairings of stimulations. ex. if one pathway is weakly activated but neighboring pathway is strongly activated, both synaptic pathways undergo LTP. One cell is tetanus and the other one is co-firing -> LTP at both |
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Term
| Testing Schaffer collatarel circuit |
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Definition
| pre-stimulate (strong=tetanus) for pathway 1. then test-stimulate pathway 1 and 2... only synapses at pathway 1 show LTP = synapse specific. Paired stimulation of pre/post is same as tetanus. |
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Term
| LTP selectivity (NMDA receptor) |
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Definition
| NMDA is permeable to Ca2+ but is blocked by Mg2+. If receptor receives glutamate but if post is at resting membrane state, NMDA is still blocked by Mg and won't open while AMPA opens--mediated by AMPA. When post is depolarized (high frequency stimulation) will cause summation of EPSPs->prolonged depolarizations and Mg goes out, letting Ca come in -> increase in Ca in dendritic spines is trigger for LTP |
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Term
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Definition
| NMDA receptor opens to induce LTP only when glutamate is bound to receptor AND postsynaptic cell is depolarized to relieve Mg block of channel pore. |
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Term
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Definition
| rise in Ca2+ in post CA1 (through NMDA) serves as second messenger that induces LTP. does this by activating complicated cascades... CaMKII and PKC |
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Term
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Definition
| most abundant postsynaptic protein at Schaffer synapses and inhibition of it prevents LTP. able to phosphorylate itself... possibly why it can prolong duration of LTP. targets may include AMPA receptors. |
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Term
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Definition
| After Ca comes in... and activates CaMKII...leads to insertion of new AMPA receptors in postsynaptic spine, increasing its sensitivity to glutamate |
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Term
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Definition
| synapses that don't respond at normal resting membrane potential but one depolarized, can transmit robust electrical responses. silence is due to voltage-dependent blockade of NMDA receptors by Mg. glutamate, at these synapses, ONLY binds to NMDA receptors. how does it avoid AMPA? AMPA more low-affinity so conc arent high enough or AMPA are not functional, or only have NMDA (latter seems to be more true) |
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Term
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Definition
| initiated by PKA which activates transcription factors like CREB (stimulates other proteins)... goes to nucleus to affect gene expression |
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Term
| LTD: Schaffer collaterals |
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Definition
| occurs when Schaffer collaterals are stimulated at a low rate (about 1 Hz) for long periods (10-15 minutes). depresses EPSP and specific to activated synapses. |
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Term
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Definition
| LTD can reverse increase in EPSP by LTP and vice versa. LTP can erase decrease in EPSP by LTD. reversibly affect synaptic efficiency by acting at common site |
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Term
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Definition
| result from activation of Ca-dependent phosphatases that cleave phosphate groups from target moelcules. associated with a loss of synaptic AMPA receptors (internalization of AMPA receptors into postsynaptic cell due to clathrin-dependent endocytosis mechanisms |
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Term
| LTD in cerebellar Purkinje cells |
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Definition
| Purkinje cells receive input from climbing and parallel fibers. LTD reduces strength of transmission at parallel fiber synapse and climbing fiber as well. associative, occurs only when climbing and parallel activated at same time |
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Term
| LTD molecular basis in cerebellar Purkinje cell |
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Definition
| parallel -> glutamate activates AMPA and metabotropic receptors. membrane depolarization + IP3 & DAG. climbing fiber -> influx of Ca.... work together to increase Ca more and activate PKC. AMPA phosphorylated by PKC and this causes internalization. decreases response of cell to glutamate release |
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Term
| spike timing-dependent plasticity |
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Definition
| requirement for precise timing between presynaptic and postsynaptic activity for induction of these long-lasting synaptic plasticity. has to do with Ca levels. if pre is before, then ca can rush in with the EPSP = LTP. if post is before... less Ca will flow in when EPSP comes from pre = LTD |
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Term
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Definition
| LTP requires high-frequency activity while LTD is induced by low-frequency activity |
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Term
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Definition
| at given low frequency synaptic activity, ltd will occur if presynaptic activity is preceded by postsynaptic action potential (post is 40 ms or less before pre) |
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Term
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Definition
| LTP occurs if postsynaptic action potential follows presynaptic activity (pre is 40 ms or less before) |
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Term
| Vesicle & Membrane proteins |
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Definition
| Synaptobrevin and synaptotagmin (calcium detector) are on the vesicle. Snap and syntaxin are on the membrane. lock up and once calcium enters, fuse with the membrane |
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