Long-lasting forms of synaptic plasticity such as long-term potentiation (LTP) and long-term depression (LTD) have been long thought and now convincingly demonstrated to be fundamental cellular mechanisms in the brain that underlie learning and memory processes. Indeed, induction of LTP is observed coincidently with learning events in the hippocampus of free-moving animals and this learning-induced LTP occludes subsequent electrical induction of LTP in the hippocampus (Whitlock et al., 2006). Conversely, saturation of LTP in the hippocampus interferes with spatial memory formation (Barnes et al., 1994). A recent work demonstrates that in vivo artificial induction of LTD impaired recall of the associative memory while subsequent LTP induction
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Upon plasticity-inducing synaptic inputs, Ca2+ entry through NMDA-type receptors (NMDARs) plays a critical role in onset of LTP, leading AMPA receptor (AMPAR) recruitment to the potentiated postsynaptic sites (Collingridge et al., 1983;Kessels and Malinow, 2009). Furthermore, the NMDAR-Ca2+ influx also plays an important role in stabilization of LTP through activation of intracellular signaling cascades from synapses to the nucleus, which in turn activate new mRNA and protein synthesis (Kandel, 2001). Blocking these steps by NMDAR antagonists (e.g. APV) or protein synthesis inhibitors (e.g. anisomycin) results in failure of establishing persistent LTP and also impairment in formation of long-term memory (Gold, 2008;Redondo and Morris, 2011). Thus, the genes induced during LTP are thought to, at least in part, encode plasticity-related proteins (PRPs) that are required for LTP maintenance and memory formation. If so, what are identities of genes encoding those PRPs? A subset of the plasticity-evoked stimuli-induced genes, which is called immediate early genes (IEGs), has been attracting attention of molecular neuroscientists because of rapid and transient responsiveness of mRNA expression in response to synaptic activation. For examples, expression of IEGs such as egr-1(zif268/krox-24), c-fos and Arc (arg3.1), is
Upon plasticity-inducing synaptic inputs, Ca2+ entry through NMDA-type receptors (NMDARs) plays a critical role in onset of LTP, leading AMPA receptor (AMPAR) recruitment to the potentiated postsynaptic sites (Collingridge et al., 1983;Kessels and Malinow, 2009). Furthermore, the NMDAR-Ca2+ influx also plays an important role in stabilization of LTP through activation of intracellular signaling cascades from synapses to the nucleus, which in turn activate new mRNA and protein synthesis (Kandel, 2001). Blocking these steps by NMDAR antagonists (e.g. APV) or protein synthesis inhibitors (e.g. anisomycin) results in failure of establishing persistent LTP and also impairment in formation of long-term memory (Gold, 2008;Redondo and Morris, 2011). Thus, the genes induced during LTP are thought to, at least in part, encode plasticity-related proteins (PRPs) that are required for LTP maintenance and memory formation. If so, what are identities of genes encoding those PRPs? A subset of the plasticity-evoked stimuli-induced genes, which is called immediate early genes (IEGs), has been attracting attention of molecular neuroscientists because of rapid and transient responsiveness of mRNA expression in response to synaptic activation. For examples, expression of IEGs such as egr-1(zif268/krox-24), c-fos and Arc (arg3.1), is