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BIO 365R Lecture 12 synaptic plasticity

BIO 365R Lecture 12 synaptic plasticity -...

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Unformatted text preview: Alpha-amino-3-hydroxy-5- methyl-4-isoxzole proprionic acid (AMPA) N-methyl-D- aspartate (NMDA) Different kinetics (time courses) NMADA and AMPA receptors can be directly observed by measuring synaptic currents at very positive membrane potentials, such as at +50 mV, when magnesium does not block NMDA receptors syna pses are not strenghtene d A B s yna ps es a re s trengt hene d input 1 input 1 input 2 input 2 D ia gram to il lu st rat e Heb b's p os tul at e. In A, the n euron re ce ive s t wo input s b ut th e discha rges in ea ch input fiber oc cur at differe nt ti mes . Ea ch synaps e evoke s a parti cula r res pons e , but t he s yna pse s a re not stre ngt hene d. In B, the t wo i nput s are t em pora ll y co inc ide nt, s uch tha t th e dis cha rge s from e ac h f ibe r a rrive s a t the po st s ynapt ic c el l at t he s a me t i me . Si nc e t he a ct i vi ty i s c oi nc id en t, t he s e syna ps e s a re s tre ng th en ed . spines Pathway 1 Pathway 2 Hi frequency stimulation only of pathway 1 Excitatory Post-synaptic Potentials (EPSPs) Stimulate Schaffer collaterals at a high rate (tetanic stimulation) to depolarize post-synaptic cell Stimulate collateral with single pulse And evoke enhanced EPSP Excitatory Post-synaptic Potentials (EPSPs) Or Stimulate Shaffer collaterals at low rate but also strongly depolarize CA1 cell while the collateral is stimulated Stimulate collateral with single pulse And evoke enhanced EPSP Stimulate collateral at a low rate during this period E P S P s a r e n o w s m a lle r In active protein kinase calmodulin ++ Ca Ca-Calmodulin complex Activated calmodulin activates protein kinase ++ Ca ++ Ca Ca++ binding activates calmodulin Activated protein Kinase Activated kinase physphorylates other proteins I n a c tiv e C a /C a m K in a s e I I A c tiv a te d C a /C a m K in a s e I I Large Ca++ influx causes autophosphorylation of Ca/Cam Kinase II Why does low Ca2+ cause LTD, 2 + cau s e L T P ? but high Ca hi Ca2+ L o n g - te r m a c tiv a tio n o f Ca2+ CaM kinase (autophos) A c tiv a tio n o f p h o s p h a ta s e LTP low Ca2+ W e a k o r tr a n s ie n t a c tiv a tio n o f Ca2+ CaM kinase S tr o n g a c tiv a tio n o f p h o s p h a ta s e LTD Phosphatase has a higher affinity (i.e. is more sensitive) to Ca2+ than CaM Kinase But CaM kinase is auto-phosphorylated at high Ca2+ levels and stay on longer overcoming the phosphatase. Induction of LTP and LTD LTP Weak Stimulation Tetanic Stimulation LDP Moderate Stimulation Na+ NMDA Mg ++ Mg++ Ca++ Na+ Na+ Na+ Mg++ Ca++ Na+ Na+ AMPA P Na+ ++ Ca Na + P Na+ Ca ++ Na + Na + P Activation of protein phosphatase dendritic spin e CaM CaM KII P AMPA AMPA Terms and concepts S y n a p ti c p l a s ti c i ty , A M P A a n d N M D A glutamate receptors, CAM kinase, a u to p h o s p h o r y l a ti o n , H e b b i a n s y n a p s e , L T P , L T D , t e ta n i c s ti m u l a ti o n . ...
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