Asymmetric synapses more than double the number of symmetric synapses in the ICd.

Unlike the lemniscal ICc, asymmetric synapses are not lost with age in the ICd.

GABAergic synapses are downregulated with age in the ICd.

Terminal area for both GABAergic and asymmetric ICd synapses declined with age.

The inferior colliculus (IC) is a nucleus in the auditory midbrain that plays an important role in sound and speech processing through how it encodes temporal precision. Temporal precision depends on the balance of inhibition and excitation within the IC. This balance degrades during aging. Age-related changes in synapses have been described in the lemniscal IC as a contributing factor for this imbalance. However, it is unknown if aging affects synapses throughout the non-lemniscal IC in a similar manner. We sought to determine this by examining the dorsal cortex of the IC (ICd). The ICd is a non-lemniscal nucleus that is well known for its extensive innervation by the auditory cortex. Electron microscopy techniques were used across age groups of younger age (2–3 months), middle age (19–21 months) and older age (27–29 months) Fischer Brown Norway rats. Our data demonstrates a small loss of GABAergic synaptic density in middle age, with a significant (34 %) loss during older age. Unlike previous reports of the aging ultrastructure of the IC, asymmetric synaptic density in the ICd remained unchanged. We also demonstrate decreases with age in terminal area and mitochondrial ultrastructure across both synaptic types. Lastly, far fewer asymmetric inputs were observed onto larger GABAergic dendrites. Collectively our data suggest a net loss of inhibition in the ICd. Thus, the balance of excitation and inhibition in the ICd is likely altered and may contribute to factors underlying age-related hearing loss.

gamma-Aminobutyric acid

glutamic acid decarboxylase

central nucleus of the inferior colliculus

dorsal cortex of the inferior colliculus

lateral cortex of the inferior colliculus

inferior colliculus

dorsal cortex of the IC

GABA

synapse

aging

ultrastructure

© 2025 The Author(s). Published by Elsevier Inc.