Presynaptic Mechanisms of Plasticity
• contains synaptic vesicles filled with neurotransmitter and a dense matrix of cytoskeleton and scaffolding proteins at the site of release, the active zone
• Varying the probability of neurotransmitter release: one mechanism for altering synaptic strength during neuronal plasticity
• vesicle mobilization, docking锚靠，入坞, priming释放前需要进一步的启动反应, fusion融合, and recycling: may be regulated by activity
Postsynaptic Mechanisms of Plasticity
• dendritic spines: postsynaptic compartments • the size of the spine head and the volume of the spine correlate with synaptic strength(large
• Three sequential synaptic pathways (perforant, mossy fiber, and Schaffer collateral thways)
• high-frequency stimuli produce synaptic strengthening called long-term potentiation (LTP); • low-frequency stimuli produces synaptic weakening, LTD. • LTP and LTD can also be produced by STDP ---- the relative timing of pre- and postsynaptic spikes leads to changes in synaptic strength
cell adhesion, and stimulus-induced changes in gene expression within neurons
• excitatory neurons in the mammalian hippocampus • long-lasting forms of plasticity that underlie learning and memory
Synapsins and synaptic vesicle mobilization
• three states of synaptic vesicle: • The readily releasable pool(RRP), docked at the active zone; • The recycling pool, which can be released with moderate stimulation; • The reserve pool(RP), which is only released in response to strong stimuli
ediated interaction, thereby enabling fast, synchronous triggering of neurotransmitter release at a synapse • and interact with Munc-13 (a priming factor, required for efficient SNARE complex formation and membrane fusion), by binding to Munc13, thereby relieving Munc13 homodimerization promoted vesicle priming • PKARIM(P) , RIM1α is required for mossy fiber LTP（has a principal presynaptic component）
1) signaling from synapse to nucleus; cargoes, stimulation trigger, pathways 2) mRNA localization and regulated translation.
• cultured Aplysia sensory-motor neurons and cultured rodent hippocampal neurons • cell biological, molecular biological and electrophysiological techniques
Postsynaptic kinases in the spine: CaMKII and PKMζ (zeta)
• LTP and LTD induction are both dependent on postsynaptic [Ca2+]i↑ • LTP requiring large↑; LTD requiring smaller↑ 先后顺序（PRE/POST; POST/PRE） • [Ca2+]i↑ activates multiple downstream signaling enzymes: the kinases CaMKII and PKC…
spine heads containing more neurotransmitter receptors, reflecting greater synaptic strength) • Spines serve as compartmentalized signaling units, and the number and shape of spines change
plasticity • 内源性激酶和磷酸酶的活性 可能调节phosphorylate synapsins 。。
RIM proteins and synaptic vesicle docking and priming
• calcium influx • vesicle and plasma membrane soluble NSF-attachment protein receptor(SNARE) proteins are
Hippocampal Synaptic Plasticity
• tractable experimental model system: a defined population of identifiable neurons and be amenable to electrophysiological, genetic, and molecular cell biological manipulations.
• Ca2+-bound calmodulin↑ CaMKII autoP • Neuronal activity translocates CaMKII to the PSD P many PSD proteins, including glutamate
receptors
• LTP induction(CA1), requires CaMKII activity: transgenic mice lacking the α isoform have defective LTP and spatial learning
CaMKII（合成调控？）
• Calcium/calmodulin-dependent protein kinase II(CaMKII) is a Ca2+-activated enzyme, abundant in the brain, constitutes 1–2% of the total protein. enriched at synapses, a main protein of the postsynaptic density(PSD)
alter the number of synaptic vesicles available for release • Synapsin knockout mice: reserve pools of synaptic vesicles↓ . deficits in learning and memory & various forms of
• synapsins tether synaptic vesicles to the actin cytoskeleton and to one another • Neuronal stimulation activates kinases phosphorylate synapsins modulate synaptic vesicle tethering
LTP
• Mechanistically, 3 component parts: • Induction, transient events serving to trigger the formation of LTP. • maintenance, persisting biochemical signal. • Expression, 指诱导突触传递效能改变的主要参与因素
The Cell Biology of Synaptic Plasticity
Victoria M. Ho, Ji-Ann Lee, Kelsey C. Martin
4 NOVEMBER 2011 VOL 334 SCIENCE