Age-related plasticity of the axon initial segment of cortical pyramidal cells in marmoset monkeys

Structural plasticity of the axon initial segment (AIS), the site of action potential initiation, is observed as part of the normal early development of the cortex, as well as in association with injury and disease. Here, we show that structural AIS plasticity also occurs with normal aging in adult marmosets. Immunohistochemical techniques were used to reveal the extent of the AIS of layer 2/3A pyramidal cells in 8 neocortical areas. We found that the AIS length varied significantly between areas in young adult (2–3 years old) marmosets, with neurons in frontal area 14C having the longest AIS, and those in the primary visual cortex the shortest. Similar interareal differences were observed in aged (12–14 year old) monkeys, but the AIS was significantly shortened in many areas, relative to the corresponding length in young adults. Shortening of the AIS is likely to represent a compensatory response to changes in the excitation-inhibition balance, associated with the loss of GABAergic interneurons in the aged cortex.