Homeostatic changes maintain the gain control of spinal motoneurones across the lifetime of C57BL/6J mice

Abstract

Age-related changes in the excitability of spinal motoneurone have been observed in mouse models of neurodegenerative diseases affecting these neurones. How the excitability of spinal motoneurones change with healthy ageing in mice and how this compares with that seen in neurodegenerative diseases is unknown. Therefore, we performed in vivo intracellular recording from identified spinal motoneurones in C57BL/6 mice at three different ages (100, 300-400 and 600-750 days old). Behavioral tests confirmed a linear reduction in motor function across these ages (using the rotorod test). Significant differences were observed with respect to the features of individual somatic action potential with ageing including a decreased rate of rise and fall in aged mice. Surprisingly, the rate of rise of the action potential at the initial segment was altered in middle aged mice. Immunohistochemical labelling of the axon initial segment of the motoneurones confirmed structural changes occurring at middle age (decreased length and diameter) but returning to the earlier parameters in aged mice. To explore the effects on repetitive firing, this was tested across the age groups which showed surprising little difference as the mice aged, with a similar rheobase and I-f gain across all age groups (with the exception of a lower voltage threshold for action potential initiation in middle-aged mice). However, amplitudes of the after-hyperpolarization and the input resistance were both found to be significantly altered with age. We conclude that there are changes occurring in the intrinsic properties of spinal motoneurones that control their excitability over the lifetime of mice, although these do not develop in a linear fashion from young to old. We propose that these changes are homeostatic in nature and are able to compensate for one another to maintain a constant gain control across the lifetime.