Differences in hippocampal CREB phosphorylation in trace fear conditioning of two inbred mouse strains

Yoo Kyeong Hwang, Jae Chun Song, Seol Heui Han, Jeiwon Cho, Dani R. Smith, Michela Gallagher, Jung Soo Han

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11 Scopus citations


The effects of genetic background on fear trace conditioning were evaluated in relation to phosphorylated levels of cAMP response element-binding protein (CREB) in the hippocampus using two different inbred strains of mice, C57BL/6 and DBA/2. The male mice received a trace fear conditioning protocol and unpaired control groups were included to assess nonassociative effects on test performance. Both C57BL/6 and DBA/2 mice with paired training displayed higher freezing responses during testing than those with unpaired training, respectively. The C57BL/6 mice with paired training also displayed higher freezing responses to the tone-CS during testing than the DBA/2 mice with paired training. Because much evidence implicates the hippocampus as an important neural substrate for trace fear conditioning, the engagement of the hippocampus was examined after testing by measuring levels of CREB and phosphorylated CREB (pCREB). The results revealed that hippocampal CREB levels in both strains of mice were not significantly altered according to the type of training (unpaired vs. paired). However, the hippocampal pCREB levels were significantly higher in the paired training group than the unpaired control group in C57BL/6 mice, but not in DBA/2 mice. These findings indicate that hippocampal pCREB is closely tied to this form of associative conditioning only in C57BL/6 mice and that different neural substrates may support trace conditioning in C57BL/6 and DBA/2 strains.

Original languageEnglish
Pages (from-to)156-163
Number of pages8
JournalBrain Research
StatePublished - 23 Jul 2010

Bibliographical note

Funding Information:
This work was supported by research grant from Institute of Biomedical Science and Technology, Konkuk University ( 2007 ) to Seol-Heui Han and the Korea Research Foundation Grant funded by the Korean Government (MOEHRD), Basic Research Promotion Fund ( KRF-2009-0075581 ) to Jung-Soo Han, and NCRR grant 1PO40 RR017688 to Michela Gallagher.


  • Hippocampus
  • Mice
  • Phosphorylated CREB (pCREB)
  • Trace fear conditioning
  • cAMP response element-binding protein (CREB)


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