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

Abstract

Presbycusis, one of the most widespread disorders, is in part associated with the loss of temporal precision within the central auditory system. A contributor to the dysfunctional temporal precision during aging is the substantial downregulation of GABA in the central inferior colliculus (ICc), the hub of ascending and descending inputs of the auditory midbrain. However, how GABAergic inputs across the tonotopic axis of the ICc change with age has not been well explored. We sought to determine age-related changes to GABAergic synapses in the lemniscal ICc, and if changes are uniform across the ICc axis. Using immuno-electron microscopy across four age groups of Fisher Brown Norway rats, a model that acquires low frequency presbycusis, our results demonstrate several nonuniform ultrastructural changes to GABAergic synapses in the ICc. There was a significant (∼29–33 %) downregulation of GABAergic synapses in the high and middle frequency regions of old rats, but a loss (∼22 %) in the old low frequency region was not as robust and did not reach statistical significance. Interestingly, in the high and middle frequency regions, GABAergic presynaptic area increased with age, while there was an ultimately decline in the old low frequency region. Also unique to the high and middle frequencies was the increasing proportion of GABAergic synapses onto larger GABAergic dendrites. These changes demonstrate that aging differentially affects the GABAergic ultrastructure of the ICc tonotopic axis.