201. An egr-1 (zif268) antisense oligodeoxynucleotide infused into the amygdala disrupts fear conditioning
- Author
-
Seema Malkani, Karin J. Wallace, Jeffrey B. Rosen, and Melanie P. Donley
- Subjects
Male ,medicine.medical_specialty ,Microinjections ,Cognitive Neuroscience ,Conditioning, Classical ,Environment ,Amygdala ,Immediate early protein ,Immediate-Early Proteins ,Oligodeoxyribonucleotides, Antisense ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,Memory ,Internal medicine ,medicine ,Avoidance Learning ,Animals ,Fear conditioning ,Freezing Reaction, Cataleptic ,Transcription factor ,Early Growth Response Protein 1 ,Dose-Response Relationship, Drug ,Association Learning ,Membrane Proteins ,Fear ,Research Papers ,Rats ,body regions ,DNA-Binding Proteins ,Dose–response relationship ,Freezing behavior ,Neuropsychology and Physiological Psychology ,Endocrinology ,medicine.anatomical_structure ,Odor ,Conditioning ,Psychology ,Carrier Proteins ,Neuroscience ,hormones, hormone substitutes, and hormone antagonists ,Transcription Factors - Abstract
Studies of gene expression following fear conditioning have demonstrated that the inducible transcription factor, egr-1, is increased in the lateral nucleus of the amygdala shortly following fear conditioning. These studies suggest that egr-1 and its protein product Egr-1 in the amygdala are important for learning and memory of fear. To directly test this hypothesis, an egr-1 antisense oligodeoxynucleotide (antisense-ODN) was injected bilaterally into the amygdala prior to contextual fear conditioning. The antisense-ODN reduced Egr-1 protein in the amygdala and interfered with fear conditioning. A 250-pmole dose produced an 11% decrease in Egr-1 protein and reduced long-term memory of fear as measured by freezing in a retention test 24 h after conditioning, but left shock-induced freezing intact. A larger 500-pmole dose produced a 25% reduction in Egr-1 protein and significantly decreased both freezing immediately following conditioning and freezing in the retention test. A nonsense-ODN had no effect on postshock or retention test freezing. In addition, 500 pmole of antisense-ODN infused prior to the retention test in previously trained rats did not reduce freezing, indicating that antisense-ODN did not suppress conditioned fear behavior. Finally, rats infused with 500 pmole of antisense-ODN displayed unconditioned fear to a predator odor, demonstrating that unconditioned freezing was unaffected by the antisense-ODN. The data indicate that the egr-1 antisense-ODN interferes with learning and memory processes of fear without affecting freezing behavior and suggests that the inducible transcription factor Egr-1 within the amygdala plays important functions in long-term learning and memory of fear.
- Published
- 2004