Specific induction of early growth response gene I in the lateral nucleus of the amygdala following contextual fear conditioning in rats

Although the amygdala is known to be crucial for fear conditioning, Little is known about the molecular and cellular mechanisms in the amygdala that a re important for fear conditioning. One possible mechanism may be the activ ation of immediateearly genes, which function as regulatory factors of tran scriptional processes. To investigate whether one of the major immediateear ly gene families is involved in the learning and memory of fear, we examine d the effects of fear conditioning on the expression of the four members of the early growth response (EGR) gene family, EGR-1, EGR-2, EGR-3, and EGR- 4. Image analysis of in situ hybridization of messenger RNA of the four fam ily members was performed in the amygdala, hippocampus, and neocortex 15, 3 0 and 60 min following one-trial contextual fear conditioning. Rats were ei ther handled, placed within the testing context without receiving the foots hock, and received a footshock immediately upon placement within the contex t, or received a footshock after a 3-min delay (delayed-shock). Of the four groups, only the delayed-shock group exhibited a fear response (freezing). EGR-1 messenger RNA expression in the dorsolateral part of the lateral amy gdaloid nucleus was significantly greater in the delayed-shock group compar ed with the other groups 15 and 30 min following the conditioning. The incr eased expression of EGR-1 was specifically localized to the lateral nucleus of the amygdala; expression in the hippocampus and cortex was not increase d by fear conditioning. In contrast, the expression of EGR-2, EGR-3, and EG R-4 messenger RNA was not increased in the amygdala, hippocampus or cortex following fear conditioning. In addition, following a retention test conduc ted 24 h after fear conditioning, no increases were found in the expression of EGR-1 messenger RNA expression in the amygdala, hippocampus or cortex. The results demonstrate that of the four genes of the EGR family of transcr iption-regulatory factors, only EGR-4 messenger RNA in the dorsolateral por tion of the lateral nucleus of the amygdala was specifically increased with contextual fear conditioning. It is suggested that EGR-1 plays a functiona l role during learning, but not retrieval, of contextual fear within the la teral nucleus of the amygdala. (C) 2000 IBRO. Published by Elsevier Science Ltd.