Presbycusis and the Deterioration of Neural Nets

By Khaleel A. Razak, Ph.D.

This shows cells of the auditory cortex from a young mouse. Cells can be parvalbumin positive (red), or perineuronal positive (green), or have both parvalbumin and perineuronal nets (red surrounded by green). In our paper we show that all three cell types decline with presbycusis. These changes can cause functional deficit in auditory processing.

This shows cells of the auditory cortex from a young mouse. Cells can be parvalbumin positive (red), or perineuronal positive (green), or have both parvalbumin and perineuronal nets (red surrounded by green). In our paper we show that all three cell types decline with presbycusis. These changes can cause functional deficit in auditory processing.

Age-related hearing loss, or presbycusis, affects a third of the population ages 65 and older, and nearly half the population older than age 75. As a result, it is one of the most prevalent hearing disorders, and it also has a high potential for associated tinnitus and deficits in speech recognition.

Presbycusis leads to myriad changes in the central auditory nervous system. One consistent change is the decline in the ability of auditory system neurons to transmit and receive information with precise timing. The timing precision is somewhat like time-stamping a sound, helping to locate and decode it.

As a result, because of changes to the both the inner ear as well as to the central brain regions that process sound, a combination of hearing aids, behavioral training, and pharmacological treatments will be necessary to alleviate presbycusis-related processing deficits. A key step in developing such a combination method is to understand the mechanisms underlying the changes in neurotransmission in the auditory system and to determine how these changes affect sound processing.

Our paper “Age-Related Deterioration of Perineuronal Nets in the Primary Auditory Cortex of Mice,” which was published in the journal Frontiers in Aging Neuroscience, focuses on a specialized structure in sensory cortex known as perineuronal nets (PNNs). Made up of large molecules, PNNs are like a mesh helping to stabilize synapse function among neurons. These extracellular matrix components preferentially surround inhibitory neurons in the auditory cortex and are known to be critical to the function and survival of the neurons they surround.

Specifically, a group of neurons known as parvalbumin-expressing (PV+) neurons are surrounded by PNNs. PV+ neurons play a role in network synchronization and providing inhibition that shapes precise temporal encoding. Reduction in the function of PV+ neurons can lead to the processing deficits observed in presbycusis.

Using two different mouse models, we show that PNN expression is reduced with age, and that an age-related decline in PNNs with presbycusis may be related to changes in synapse function, affecting the processing of sound, particularly those that require proper timing. Because PNNs can be pharmacologically regulated, future studies will test if deterioration of PNNs with presbycusis can be delayed or prevented.

Khaleel A. Razak was a 2009 and 2010 Hearing Health Foundation Emerging Research Grants recipient. This study was started with funding by the Hearing Health Foundation in 2009-2010.

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