Analyses of fear memory in Arc/Arg3.1-deficient mice: intact short-term memory and impaired long-term and remote memory

Abstract

Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) was originally identified in patients with seizures. It is densely distributed in the hippocampus and amygdala in particular. Because the expression of Arc/Arg3.1 is regulated by nerve inputs, it is thought to be an immediate early gene. As shown both in vitro and in vivo, Arc/Arg3.1 is involved in synaptic consolidation and regulates some forms of learning and memory in rats and mice [1,2]. Furthermore, a recent study suggests that Arc/Arg3.1 may play a significant role in signal transmission via AMPA-type glutamate receptors [3-5]. Therefore, we conducted a detailed analysis of fear memory in Arc/Arg3.1-deficient mice. As previously reported, the knockout animals exhibited impaired fear memory in both contextual and cued test situations. Although Arc/Arg3.1-deficient mice showed almost the same performance as wild-type littermates 4 hr after a conditioning trial, their performance was impaired in the retention test after 24 hr or longer, either with or without reconsolidation. Immunohistochemical analyses showed an abnormal density of GluR1 in the hippocampus of Arc/Arg3.1-deficient mice; however, an application of AMPA potentiator did not improve memory performance in the mutant mice. Memory impairment in Arc/Arg3.1-deficient mice is so robust that the mice provide a useful tool for developing treatments for memory impairment.

CB1R-Mediated Activation of Caspase-3 Causes Epigenetic and Neurobehavioral Abnormalities in Postnatal Ethanol-Exposed Mice

“…Together, these events can alter H3K9me2 and H3K14ace (Basavarajappa and Subbanna, 2016 ) to repress Arc expression. These findings provide epigenetic mechanisms for the P7 ethanol-induced long-lasting Arc expression deficits, which are a significant part of synaptic function and cognitive behavior (Donai et al, 2003 ; Chowdhury et al, 2006 ; Bramham et al, 2008 ; Kawashima et al, 2009 ; Korb and Finkbeiner, 2011 ; Yamada et al, 2011 ; Dyrvig et al, 2012 ). It should be emphasized here that ethanol-induced inhibition of the CB1R-regulated ERK1/2-pCREB-Arc signaling pathway might disrupt the proper development of synaptic circuits, leading to lasting synaptic, learning and memory defects (Abel et al, 1983 ; Bonthius and West, 1991 ; Bellinger et al, 1999 , 2002 ; Berman and Hannigan, 2000 ; Alati et al, 2006 ; Brown et al, 2007 ; Brady et al, 2013 ; Subbanna et al, 2013a , 2015a ; Subbanna and Basavarajappa, 2014 ; Basavarajappa, 2015 ).…”

Role of Immediate-Early Genes in Synaptic Plasticity and Neuronal Ensembles Underlying the Memory Trace

“…Arc expression is required for LTM consolidation, but not for learning or short-term memory formation (STM; Plath et al, 2006 ). Arc knockout (KO) mice exhibit impaired consolidation of spatial and fear memories ( Plath et al, 2006 ; Peebles et al, 2010 ; Yamada et al, 2011 ). Transient inhibition of Arc expression following infusion of Arc antisense oligodeoxynucleotides (ODNs) into the hippocampus, lateral amygdala, or anterior cingulate cortex inhibits memory consolidation ( Guzowski et al, 2000 ; Ploski et al, 2008 ; Holloway and McIntyre, 2011 ; Nakayama et al, 2015 ).…”

Immediate Early Genes, Memory and Psychiatric Disorders: Focus on c-Fos, Egr1 and Arc

“…A genetic KO for arc expression generates deficits in the consolidation of different types of long-term memories (spatial, fear and episodic-like) together with changes in long-term plasticity (Plath et al, 2006 ; Peebles et al, 2010 ; Yamada et al, 2011 ). In addition, a significant correlation between arc mRNA expression and behavioral performance was found during spatial reversal task suggesting a role in cognitive flexibility (Guzowski et al, 2001b ).…”