Segunda Parte: El camino de vuelta Del núcleo a la ... 6. Comunicacion... · ‐CPE – CPEB:...
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Transcript of Segunda Parte: El camino de vuelta Del núcleo a la ... 6. Comunicacion... · ‐CPE – CPEB:...
Cómo llegan las macromoléculasa las sinapsis específicas?a las sinapsis específicas?
Hipótesis para explicar la especificidad sináptica
Synaptic Tagging
New gene
New gene products or
products or proteins
products or proteins
Synaptictag
NMDAR
Signal to nucleus Synaptic
Potentiation
NMDAR
Locally generated tag captures new gene d tproduct
Ejemplos de síntesis local en plasticidad neuronal:Ejemplos de síntesis local en plasticidad neuronal:
‐Facilitación por 5 HT en Aplysia‐‐Síntesis de Activity regulated cytoskeleton asociated p. (Arc) ‐y g y p ( ) ‐ Síntesis de CaMKIIα‐Síntesis de PKMz
Síntesis proteica localMartin et al Cell 91:927-38 (1997)
Sistema de neurona sensorial bifurcada
Martin et al., Cell 91:927 38 (1997)
Mecanismos de transporte de mRNAs:A través de unión de mRNA BP a secuencias 3´ UTR
‐Zip codes sequences ZBP: actina‐CPE – CPEB: αCaMKII SeminarioFMRP St f‐FMRP – Staufen
(sería un mecanismo de captura de mRNA a las sinapsis)
Localización en el tiempo de Arc mRNALocalización en el tiempo de Arc mRNA
Steward and Worley, PNAS 2001
Domain Structures of Isoforms of PKC
Regulatory Domain Catalytic Domain
α alphaβΙ/βΙΙ Betaγ Gamma
ClassicalCalcium ATP SubstratePhospholipidPS
Auto
Novel
γ Gamma•• •• •• Auto‐
phosphorylation sites
δ Deltaε Epsilonη Etaθ Thetaµ Muµ Mu
Atypical
λ/ι Lambda/Iota ζ Zeta
yp
Hinge Region
Figure 1. Effect of ZIP on very long term CTA memory in the insular cortex. (A) ZIP/vehicle ‐were administered 3 mo after training, and memory was tested 2 d later. The dashed line indicates equal preference for the CS and water, i.e., AI = 50. (B) ZIP/vehicle/scrambled ZIP
d i i t d 1 ft t i i d t t d 12 d l t S h i thwere administered 1 mo after training, and memory was tested 12 d later. Saccharin was the CS in both A and B. Shema et al., Learning & Memory 2009
ZIP abolishes very long term memory‐
The effect of ZIP is long lasting even when the inhibitor is applied long after encoding
Intensive training and robust memory do not confer immunity to ZIP effect
Once erased and reacquired, CTA can be erased again by ZIPerased again by ZIP
Intensive training and robust memory do not confer immunity to ZIP effecty
ZIP is ineffective during conditioning and immediately afterwardimmediately afterward