Inducible cAMP early repressor acts as a negative regulator for kindling epileptogenesis and long-term fear memory.
Long-lasting neuronal plasticity as well as long-term memory (LTM) requires de novo synthesis of proteins through dynamic regulation of gene expression. cAMP-responsive element (CRE)-mediated gene transcription occurs in an activity-dependent manner and plays a pivotal role in neuronal plasticity and LTM in a variety of species. To study the physiological role of inducible cAMP early repressor (ICER), a CRE-mediated gene transcription repressor, in neuronal plasticity and LTM, we generated two types of ICER mutant mice: ICER-overexpressing (OE) mice and ICER-specific knock-out (KO) mice. Both ICER-OE and ICER-KO mice show no apparent abnormalities in their development and reproduction. A comprehensive battery of behavioral tests revealed no robust changes in locomotor activity, sensory and motor functions, and emotional responses in the mutant mice. However, long-term conditioned fear memory was attenuated in ICER-OE mice and enhanced in ICER-KO mice without concurrent changes in short-term fear memory. Furthermore, ICER-OE mice exhibited retardation of kindling development, whereas ICER-KO mice exhibited acceleration of kindling. These results strongly suggest that ICER negatively regulates the neuronal processes required for long-term fear memory and neuronal plasticity underlying kindling epileptogenesis, possibly through suppression of CRE-mediated gene transcription.
Kojima
Nobuhiko
N
Unit for Molecular Neurobiology of Learning and Memory, Okinawa Institute of Science and Technology, Uruma, 904-2234, Japan.
Borlikova
Gilyana
G
Sakamoto
Toshiro
T
Yamada
Kazuyuki
K
Ikeda
Toshio
T
Itohara
Shigeyoshi
S
Niki
Hiroaki
H
Endo
Shogo
S
D000818:Animals; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics / Q000502:physiology*; D004827:Epilepsy / Q000235:genetics / Q000378:metabolism*; D005239:Fear / Q000502:physiology*; D005260:Female; D007696:Kindling, Neurologic / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009433:Neural Inhibition / Q000502:physiology; D012097:Repressor Proteins / Q000502:physiology*
D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator