Abstract
Problem: C-fos, an early signaling gene, is activated in the cochlear nucleus by novel sound in a tonotrophic distribution and is associated with novelty-adaptation. (1) C-fos expression in neurons follows long-term potentiation (LTP) and is an early indicator of memory consolidation. (2) Adrenergic receptor activation, required for long-term potentiation, has been shown to affect memory storage. (3,4) Mapping c-fos expression in the cochlear nucleus by immunohistochemistry is a reliable indicator of tone-evoked excitation in auditory brainstem neurons. (5) Our objective was to examine alterations in c-fos expression in the rat dorsal cochlear nucleus following novel auditory stimulation after injection with norepinephrine.
Methods: Taconic rats were conditioned by keeping them in a quiet room for 12 hours and then injected with norepinephrine (24 μg) or normal saline (control). They were then subjected to novel 70-dB tone bursts for 1 hour and then sacrificed. Immunohistochemical localization of the c-fos protein was performed on sections through the center of the cochlear nucleus.
Results: Twenty-seven rats in the experimental group and eighteen control rats were studied. The average cell count in the experimental group was 74.92 cells per 50-μm section, with a standard deviation of 26.03. In the control population the average cell count was 50.05 with a standard deviation of 21.53. Comparison of the two means with a Student t test yielded a P value of 0.001.
Conclusion: Norepinephrine increased significantly (49.7%) the expression of Fos protein within the dorsal cochlear nuclei of rats stimulated with novel sound patterns. This study shows that the auditory c-fos response to novel sound can be enhanced by norepinephrine, further suggesting that this signal gene may couple LTP to memory through synaptic plasticity to signal novel sound adaptation.
Significance: Neuronal plasticity, the ability of neurons to change and adapt in response to environmental stimuli, is central to understanding learning behavior and memory.
Support: NIH Grant NS-13742 and AG-09480