The brain makes use of sensory information in order to form memories. Loss of hearing has an impact on the aging brain, as suggested by the correlation between onset of age-related deafness and onset of dementia. While it is possible that this reflects common processes of neurodegeneration, as age-related deafness appears to result from loss of neural connections between sensory hair cells and the brain, studies such as this one provide evidence for deafness to cause greater loss of function in areas of the brain associated with memory formation.

Brain structures that are essential for the acquisition and encoding of complex associative memories, such as the hippocampus, use spatial sensory information both to generate metric representation of navigable space and to create robust and long-lasting records of spatial experience. The latter is enabled by hippocampal synaptic plasticity, and it has been shown that visuospatial, olfactospatial, and audiospatial experience can be used by the hippocampus to create spatial memories.

Studies of the consequences of loss of visual input and blindness have shown that adaptation occurs as a consequence of extensive reorganization of the cortex that reflects both changes in the affected primary sensory cortex and in other primary and associative sensory areas. One aspect of this that has received little attention is how the cortex and hippocampus functionally adjust to initial loss of input from a specific sensory modality. Recently, we reported that hereditary blindness that becomes manifest in mice within weeks after birth results in massive and progressive reorganization of neurotransmitter receptor expression in the cortex and hippocampus that persists for months after the onset of blindness. This reorganization is accompanied by a profound impairment of hippocampal long-term potentiation (LTP) and debilitation of hippocampus-dependent spatial learning.

Ultimately, both humans and animals recover from this transitional phase. Recent studies in human individuals have suggested, however, that the consequences for cognition of gradual sensory loss are insidious. Age-dependent sensorineural hearing loss (presbycusis) comprises a gradual and cumulative loss of hearing sensitivity. It is closely associated with cognitive decline and is considered a risk factor for dementia.

A causal link between cumulative hearing loss and cognitive decline is currently lacking. In the present study, our goal, therefore, was to explore to what extent a gradual loss of hearing sensitivity can result in cortical reorganization and changes in hippocampal function. The C57BL/6 mouse strain develops cumulative deafness that first becomes manifest at the age of 4 weeks. We show here that widespread changes in plasticity-related neurotransmitter expression become manifest as early as at 2 months of age in C57BL/6 mice. At 4 months of age, neurotransmitter receptor changes occur in both primary sensory and association cortices and also extend to the hippocampus. At this time-point, potent impairments in hippocampal LTP and spatial memory become evident.

The data indicate that gradual hearing loss is accompanied by extensive adaptive changes in the cortex and hippocampus that hinder effective hippocampal information processing and suggest that progressive hearing loss may be causally linked to cognitive decline.