Electrophysiological evidence for axonal degeneration of locus coeruleus neurons following long-term forced running stress

Using electrophysiological methods, a change in the density of axon terminals of locus coeruleus (LC) neurons in the cerebral cortex of rats following long-term forced running stress was examined. The stressed animals were classified into two groups based on spontaneous running activity (SRA) measured for 2 weeks after the stress treatment: 1) animals showing early restoration of SRA (poststress active rat) and 2) animals showing little or no SRA (poststress inactive rat). To quantify the density of LC axon terminals in the cerebral cortex, the percentage of LC neurons antidromically activated by cortical stimulation (projection index, P-index) was assessed. The P-indices for the cortex decreased in the poststress inactive rats. Since the threshold currents for antidromic activation were not altered by the stress treatment, the observed change was considered to reflect a change of the density of LC axon terminals rather than physiological consequences. Therefore, when animals receive a prolonged, severe stress, LC neurons in a certain group of the animals may cause axonal retraction or degeneration in the cerebral cortex.