Persistent neural activity regulates Arc/Arg3.1 transcription in the dentate gyrus.
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.
Toyoda
Takeshi
T
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Science, The University of Tokyo, Tokyo, Japan.
Nomura
Hiroshi
H
Hashikawa
Koichi
K
Nonaka
Ayako
A
Matsuki
Norio
N
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009924:Organ Culture Techniques; D011963:Receptors, GABA-A / Q000502:physiology; D011976:Receptors, Muscarinic / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D015533:Transcriptional Activation / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; D011976:Receptors, Muscarinic; C092069:activity regulated cytoskeletal-associated protein