Inhibition of Activity-Dependent Arc Protein Expression in the Rat Hippocampus Impairs the Maintenance of Long-Term Potentiation and the Consolidation of Long-Term Memory

By John Guzowski, G. Lyford, G. Stevenson, F. Houston, James McGaugh, P. Worley, C. A. Barnes. Journal of Neuroscience, 2000

1,037 citations recorded by the source corpus.

It is widely believed that the brain processes information and stores memories by modifying and stabilizing synaptic connections between neurons. In experimental models of synaptic plasticity, such as long-term potentiation (LTP), the stabilization of changes in synaptic strength requires rapid de novo RNA and protein synthesis. Candidate genes, which could underlie activity-dependent plasticity, have been identified on the basis of their rapid induction in brain neurons. Immediate-early genes (IEGs) are induced in hippocampal neurons by high-frequency electrical stimulation that induces LTP and by behavioral training that results in long-term memory (LTM) formation. Here, we investigated the role of the IEGArc (also termed Arg3.1) in hippocampal plasticity. Arc protein is known to be enriched in dendrites of hippocampal neurons where it associates with cytoskeletal proteins (Lyford et al., 1995).Arc is also notable in that its mRNA and protein accumulate in dendrites at sites of recent synaptic activity (Steward et al., 1998). We used intrahippocampal infusions of antisense oligodeoxynucleotides to inhibit Arc protein expression and examined the effect of this treatment on both LTP and spatial learning. Our studies show that disruption of Arc protein expression impairs the maintenance phase of LTP without affecting its induction and impairs consolidation of LTM for spatial water task training without affecting task acquisition or short-term memory. Thus, Arc appears to play a fundamental role in the stabilization of activity-dependent hippocampal plasticity.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/1126d1e421e0bd560f13462a50d4880952f283a8

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Citations in the corpus

Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. (2007, neutral): “Because the experimental reduction of calbindin, Fos, or Arc in otherwise healthy rodents elicits neuronal deﬁcits and memory impairments (Guzowski et al., 2000; He et al., 2002; Molinari et al., 1996; Plath et al., 2006; Tzingounis and Nicoll, 2006), the depletion of these factors could further…”
Elements of a neurobiological theory of hippocampal function: the role of synaptic plasticity, synaptic tagging and schemas (2006, background): “Antisense oligonucleotides to Arc are known to inhibit longterm memory (Guzowski et al., 2000).”
Neural plasticity in the ageing brain (2006, background): “Finally, Arc expression is necessary for the maintenance, but not the induction, of LTP and long-term memor”
Brain-Derived Neurotrophic Factor Induces Long-Term Potentiation in Intact Adult Hippocampus: Requirement for ERK Activation Coupled to CREB and Upregulation of Arc Synthesis (2002, background): “The MEK inhibitors were applied at a concentration (30 M) that blocks ERK activation in response to HFS-LTP in hippocampal slices.”
Synaptic Targeting by Alzheimer's-Related Amyloid β Oligomers (2004, background): “Animal model studies have shown that appropriate Arc expression is essential for LTP and long-term memory formation (Guzowski et al., 2000).”
Brain-derived Neurotrophic Factor Promotes Differentiation and Maturation of Adult-born Neurons Through GABAergic Transmission (2012, background): “Late-phase long-term potentiation and memory consolidation require expression of immediate early genes (Guzowski et al., 2000; Bozon et al., 2002).”
Stress, memory and the amygdala (2009, background): “, an immediate-early gene product implicated in hippocampal synaptic plasticity and memory consolidatio”
Molecular motors and mechanisms of directional transport in neurons (2005, background): “fcgi?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=11838">ARC ), both of which are involved in long-term potentiatio”
Arc/Arg3.1 mediates homeostatic synaptic scaling of AMPA receptors. (2006, background): “1 protein is required for learning and memory (Guzowski et al., 2000), Arc/Arg3.”
Persistence of long-term memory storage requires a late protein synthesis- and BDNF- dependent phase in the hippocampus. (2007, neutral): “The distribution and stability of ASO are consistent with other reports describing the use of intra-hippocampal oligonucleotide injections (Guzowski et al., 2000; Lee et al., 2004; Taubenfeld et al., 2001a).”
BDNF-induced local protein synthesis and synaptic plasticity. (2014, neutral): “phase of LTP without affecting its induction (Guzowski et al., 2000).”
Sparse, environmentally selective expression of Arc RNA in the upper blade of the rodent fascia dentata by brief spatial experience (2005, background): “…behavioral plasticity, are the observations that blocking the expression of Arc protein using antisense oligodeoxynucleotides interferes with the consolidation of spatial memory and the maintenance of long-term potentiation (LTP) at the perforant path–granule cell synapse (Guzowski et al., 2000).”