Age-related differences in asymmetric synapses across the central inferior colliculus in the Fischer Brown Norway rat

The rapidly aging populations of industrial countries are commonly affected by age-related hearing loss (ARHL). A broad mechanistic theme to ARHL are imbalances to excitation and inhibition in the central auditory system in response to the reduced excitatory cochlear input. Many studies on these imbalances have focused on the changes to inhibitory/GABAergic neurotransmission in the lemniscal central inferior colliculus (ICc), leading to the poor temporal processing that characterizes ARHL. One of our recent studies demonstrated that GABAergic synapses across the ICc were downregulated in a non-uniform manner. We therefore sought to determine if presumptively excitatory asymmetric synapses were also downregulated in the same non-uniform manner. We used electron microscopy (EM) and post-embedding anti-GABA immunogold histochemistry across four age groups (3-month, 19-month, 24-month, and 28-month) of Fischer Brown Norway rats to examine the ultrastructure of asymmetric synapses in the IC. Presumptively excitatory asymmetric synapses were identified by asymmetric synaptic junctions, round vesicles, and GABA-immunonegative presynaptic boutons. Our data were collected across the dorsolateral to ventromedial axis of the ICc. Our primary result is that there is a significant downregulation (∼30%) of asymmetric synapses starting in late middle-age that occurs largely in a uniform manner across the dorsolateral-ventromedial axis of the ICc. Unlike our previous study on the downregulation of GABAergic synapses in the ICc, asymmetric synapses are downregulated across the ICc axis in a more uniform manner. These data demonstrate that there is a broad and robust loss of excitatory inputs throughout the ICc.