Persistent neural activity regulates Arc/Arg3.1 transcription in the dentate gyrus.
ABSTRACT The activity-regulated cytoskeleton-associated gene (Arc, also known as Arg3.1) is an effector immediate-early gene rapidly induced by strong neural activity. Although a number of studies have revealed significant functions of Arc and Arc has come into widespread use as a neural activity marker in behavioral studies, the mechanisms regulating Arc transcription remain unclear. Here, we examined the conditions of Arc transcription in acute slices of dentate gyrus. Surprisingly, kainic acid (1 μM to 10 mM) application to slices did not induce Arc transcription, although intraperitoneal injection of kainic acid (20 mg/kg) induced robust Arc transcription. No types of high-frequency stimulation examined induced Arc transcription in acute slices. These findings indicate that Arc transcription is dramatically suppressed in acute slices of the dentate gyrus, in which background neural activity is markedly reduced. Burst stimulation increased the number of Arc-expressing cells in the presence of picrotoxin, in which excitation was maintained even after the end of stimulation. Moreover, the involvement of background neural activity in Arc transcription was tested by application of carbachol, a muscarinic receptor agonist. Carbachol also increased the number of Arc-expressing cells, which was blocked by atropine, a muscarinic receptor antagonist. Taken together, these findings suggest that persistent background activity is critical for Arc transcription.
- [show abstract] [hide abstract]
ABSTRACT: Information processing in the central nervous system (CNS) during periods of rest is crucial for lasting memories but the precise off-line neuronal population activity that contributes to long-term memory formation remains unclear. This pattern of neuronal activity during rest triggers transcription of immediate early genes such as activity regulated cytoskeletal gene (Arc). We compared the active neuronal population in the lateral amygdala of C57BL/6J mice during fear conditioning and rest periods using a large scale imaging technique, Arc cellular compartment analysis of temporal activity by fluorescence in situ hybridization (catFISH). We found that the neuronal population transcribing Arc during fear conditioning was more similar to that the population transcribing Arc after fear conditioning than before fear conditioning. The overlapping population was larger in conditioned mice that acquired associative memory than in unshocked mice and in latent inhibited mice that received shocks but did not form associative memory. Moreover, these results were confirmed using Arc/Homer 1a catFISH. Our findings indicate that Arc is preferentially transcribed in neurons that are active during fear conditioning after associative learning. This preferential transcription may contribute to the formation of long-lasting memory.Neurobiology of Learning and Memory 02/2011; 95(4):498-504. · 3.33 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Neural activity and de novo protein synthesis during a rest period following memory retrieval in the amygdala is necessary for stabilization of reactivated fear memory. Arc/Arg3.1 (Arc) expression is regulated by neural activity and is a critical protein for memory reconsolidation. However, it remains unclear whether memory retrieval alters Arc transcription during subsequent rest. In this study, the populations of mouse lateral amygdala neurons that transcribe Arc during memory retrieval and at rest were detected using Arc cellular compartment analysis of temporal activity by fluorescence in situ hybridization (Arc catFISH). Results demonstrated that memory retrieval alters the composition of neuronal populations, which activate Arc transcription during subsequent rest. Approximately 50% of neurons that transcribe Arc at subsequent rest, transcribed Arc during memory retrieval, whereas only approximately 10% of neurons that transcribed Arc during a rest period prior to memory retrieval transcribe Arc during memory retrieval. In contrast, re-exposure to the chamber induced less preferential Arc transcription in latent inhibited mice that received shocks but recalled less conditioned fear. Taken together, these findings indicate that neuronal subpopulations activated during fear memory retrieval preferentially transcribe Arc during subsequent rest in the lateral amygdala. This preferential Arc transcription may contribute to memory reconsolidation.European Journal of Neuroscience 08/2012; · 3.75 Impact Factor