The ups and downs of synaptic plasticity: influences on this particular 'market'.

摘要: In the current economic climate it is all too apparent that what goes up can also go down; same true for strength of glutamatergic excitatory postsynaptic potentials/currents (EPSPs/EPSCs). What less underlies changes when they occur. There be no doubt exquisite detail synaptic connectivity in mammalian brain suggestive its power to store and process information. Such a static image nervous system – complex though may isolation acquires deeper significance we witness ability change: synapses are plastic activity controls plasticity. This dynamic re-wiring connections now pre-eminent physiological model learning memory. Indeed, dissecting rules govern plasticity has kept investigators busy since seminal paper by Tim Bliss Terje Lomo published The Journal Physiology (Bliss & Lomo, 1973) which showed bursts high frequency, ‘tetanic’, stimulation perforant path hippocampus led persistent increase connections, phenomenon known as long-term potentiation (LTP). Since then, host other ‘learning rules’ emerged. These include depression (LTD), weakening results from low frequency stimulation, ‘theta-burst LTP’, arising trains mimic endogenous theta band hippocampus. More recently, evidence emerged precise timing repeated pre- action potentials strengthen or weaken EPSPs/EPSCs, so-called spike timing-dependent (STDP). What subcellular mechanisms underlie these rules? hippocampus, especially at CA1–Schaeffer collateral synapses, already know many forms plasticity, including LTP, LTD STDP, depend on activation N-methyl-d-aspartate receptors (NMDARs) expressed amplitude α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated EPSPs/EPSCs. cause-and-effect scenario requires signalling molecules resident synapse couple NMDAR regulate AMPAR expression. Systematic attempts identify proteins involved this have resulted catalogue hundreds (Collins et al. 2006). Among several members membrane-associated guanylate kinase (MAGUK) family, PSD-93 PSD-95, two interact specifically with NMDARs focus issue Carlisle (2008). MAGUKs represent family evolutionarily conserved across species diverse drosophila, mouse human (Funke 2005). All multicellular organisms need such intracellular communication differentiation coordinated growth. Nowhere interplay between ultrastructural more crucial than where both PSD-93/95 found. Physiology, (2008) uncovered distinct roles each LTP examining phenotype mutant mice. main ‘take home’ messages study summarized follows. When compared wild-type littermates, mice expressing form PSD-95 (Migaud 1998) display (1) impaired basal AMPAR-mediated transmission, (2) enhanced tetanus-, theta-burst-, STDP-induced (3) LTD. contrast lacking normal levels tetanus-induced but theta-burst- NMDAR-dependent As studies details matter, summary needs expanding upon. First, earlier using concluded transmission 1998; Elias While discrepancy (2006) accounted age used, reassessment conducted confirms reduced transmission. Perhaps expression mutants engenders greater capacity increasing strength. Certainly appears not only stronger, result protocols do normally give rise strength, single spike-pairing STDP. Does therefore participate pathway simultaneously limits sensitivity temporal order events? If so, somewhat surprising acute slices show transmission: one might expect ‘experiences’ (during their lives) triggered inappropriate strengthening an Thus while vitro experience-dependent vivo share common features (Whitlock 2006) remains difficult interpret contexts. respect would useful characteristics late-phase (protein synthesis-dependent) hippocampal obtained mutants. PSD-93 subtle transmission/plasticity mutants. Basal frequency-induced indistinguishable burst-induced STDP deficits apparent. indicate calcium various understanding role particular. conclusion, demonstrates opposing effects CA1 region hippocampus; however challenge emerges understand how MAGUKs regulated if part currency used determine ‘synaptic economy’.