Long lasting forms of synaptic plasticity such as long-term potentiation (LTP) and long-term depression (LTD) have been shown to be fundamental cellular mechanisms underlying learning and memory. Induction of LTP occurs concomitantly with learning in the hippocampus of freely-moving animals and is known to prevent occludes subsequent electrical induction of LTP in the hippocampus (Whitlock et al., 2006). Conversely, saturation of hippocampal LTP is also known to interfere with spatial memory formation (Barnes et al., 1994). A recent study has demonstrated that in vivo artificial induction of LTD impaired recall of associative memory, which was restored by subsequent LTP induction (Nabavi et al., 2014). Taken together, these findings suggest
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The blockade of these pathways using NMDAR antagonists (e.g. APV) or protein synthesis inhibitors (e.g. anisomycin) results in failure of the establishment of persistent LTP and impairment in formation of long-term memory (Gold, 2008; Redondo and Morris, 2011). Although these studies suggest that specific genes, induced during LTP, encode plasticity-related proteins (PRPs) required for LTP maintenance and memory formation, the identity of these genes remains unknown. A subset of plasticity-evoked, stimuli-induced genes, known as immediate early genes (IEGs), has been implicated in the above events because of their rapid and transient responsiveness to synaptic activation. For example, the expression of IEGs such as egr-1(zif268/krox-24), c-fos and Arc (arg3.1), have been shown to be rapidly upregulated (returning to baseline by 24 h) after neuronal activation associated with pharmacologically-induced convulsive and sensory stimuli as well as behavioral tasks (Morgan et al., 1987; Saffen et al., 1988; Link et al., 1995; Lyford et al., 1995). IEG-expressing neurons are known to be distributed across a wide variety of brain regions (Rosen et al., 1998; Guzowski et al., 1999; Vann et al., 2000; Hall et al., 2001; Ramirez-Amaya et al., 2005).
The blockade of these pathways using NMDAR antagonists (e.g. APV) or protein synthesis inhibitors (e.g. anisomycin) results in failure of the establishment of persistent LTP and impairment in formation of long-term memory (Gold, 2008; Redondo and Morris, 2011). Although these studies suggest that specific genes, induced during LTP, encode plasticity-related proteins (PRPs) required for LTP maintenance and memory formation, the identity of these genes remains unknown. A subset of plasticity-evoked, stimuli-induced genes, known as immediate early genes (IEGs), has been implicated in the above events because of their rapid and transient responsiveness to synaptic activation. For example, the expression of IEGs such as egr-1(zif268/krox-24), c-fos and Arc (arg3.1), have been shown to be rapidly upregulated (returning to baseline by 24 h) after neuronal activation associated with pharmacologically-induced convulsive and sensory stimuli as well as behavioral tasks (Morgan et al., 1987; Saffen et al., 1988; Link et al., 1995; Lyford et al., 1995). IEG-expressing neurons are known to be distributed across a wide variety of brain regions (Rosen et al., 1998; Guzowski et al., 1999; Vann et al., 2000; Hall et al., 2001; Ramirez-Amaya et al., 2005).