Aging-related changes in connectivity of the primary motor cortex
As the average life expectancy continues to increase globally, the scientific community must meet the parallel challenge of extending the healthy life expectancy of the ever-growing aged population. Aging-related decline in motor control is a crucial aspect of this challenge because it diminishes independence and hinders daily living abilities, leading to greater disability burden on the remaining population. While peripheral nervous and motor systems are certainly involved in this impairment, attention to those structures has come at the expense of more complete understanding of motor control by the aged central nervous system. This dissertation expands our knowledge of this area with a specific focus on the cortex. First, this has been achieved by identifying differences in steady-state structural plasticity in the primary motor cortex (M1) of young and aged mice using chronic in vivo imaging of dendritic spines, the sites of excitatory input to pyramidal neurons that process the bulk of outgoing information from this brain area. These results indicate that at baseline conditions the dendritic spines of the aged M1 are subject to increased turnover, including formation and stabilization, while enduring decreased rates of long-term survival. Secondly, ensuing work combined in vivo imaging with motor skill training and revealed that, while unsuccessful at causing learning-induced structural plasticity of dendritic spines, motor training results in a muted learning-induced structural plasticity response by the en passant boutons (EPBs) of L2/3 parvalbumin-expressing interneurons in the aged M1. These experiments also uncovered a baseline decrease in EPB density and increase in EPB size on the aged axon. Lastly, mesoscale, awake imaging equipment was designed and built to enable future study of brain-wide engagement of various cortical areas during motor learning and performance. The product of this dissertation is a greater understanding of the impact of normal aging on the M1 at the cellular and synaptic level outside of and during motor skill practice, and it also provides an avenue for further study of larger scale changes in cortical connectivity with aging.