9/5/25 Swarat Kulkarni: Physiological, Histological, and Cognitive Characterization of a Rhesus Macaque Model of Presbycusis
Neuroscience brown bag
Date: September 5, 2025
Time: 1:25- 2:15
Location: 316 Wilson Hall
Physiological, Histological, and Cognitive Characterization of a Rhesus Macaque Model of Presbycusis
Introduction: Age-related hearing loss (ARHL), also known as presbycusis, is estimated to affect nearly two‐thirds of the U.S. population over 70. Although hearing amplification and cochlear implantation are effective treatment modalities, ARHL remains significantly undertreated. Despite ARHL prevalence and relevance, current human studies do not separate this pathology from lifetime noise exposure. Laboratory macaques live in environments with minimal noise to not cause hearing dysfunction and have long lifespans, making them optimal presbycusis models.
Methods: We describe age-related auditory changes using physiological, histological, and cognitive assessments. We use two clinical, non-invasive physiological measures: distortion product otoacoustic emissions (DPOAEs) and auditory brainstem responses (ABRs). DPOAEs were measured by playing tone pairs (L1-L2: 10 dB, f2/f1 ratio: 1.22). ABRs were recorded in response to broadband chirps (0.5–32 kHz; 1.6 ms duration; 27.7/s), clicks at different presentation rates (0.001-97 kHz; 100 μs duration; 27.7-200/s), and frequency-specific tone bursts (0.5 – 32 kHz; 27.7/s) spanning the audible range in macaques. DPOAEs were analyzed for amplitude, and ABRs for threshold, amplitude, and latency. Histologically, young and aged macaque cochlea were analyzed for changes in inner hair cell (IHC), outer hair cell (OHC), and IHC ribbon synapses. Anatomy/physiology correlations were done on a frequency-specific basis using a pearson correlation. A delayed match-to-sample task was employed to test cognitive performance.
Results: Subjects were anesthetized young (YM, 6-9 years old, n = 36 ears) and old (OM, 26-35 years old, n = 20 ears) Macaca mulatta. OMs were categorized into young-old (YO; 26–30 years, n = 12 ears) and old-old (OO; 31–34 years, n = 6 ears). Aged macaques exhibited progressive cochlear degeneration, with marked OHC/IHC loss at mid-to-high frequencies, patterns of IHC synaptic ribbon loss, and reduced DPOAE amplitude. Aged macaques had altered ABR waveforms: increased auditory thresholds, wave-width changes, reduced amplitudes, prolonged latencies, and diminished temporal precision. The progressively increasing thresholds were in contrast with responses at 90 dB that did not differ, and these resulted from increased response slopes in older macaques. Structural loss was significantly correlated to physiological impairments: OHC Survival % – DP Amplitude and Mean Ribbon Count – ABR Wave I amplitude. Auditory deficits correlated with subtle impairments in visual working memory, highlighting potential sensory-cognitive links.
Discussion: The macaque patterns of OHC, IHC, and audiological decline model human studies, but macaques show less synaptopathy compared to human ANF loss. ABR results align with electrophysiological studies in aging rodents showing diminished inhibition and impaired temporal coding. This supports a sensory-driven mechanism linking hearing loss to cognitive decline, positioning macaques as valuable aging/cognition models.
Authors: Swarat Kulkarni, Amy Stahl, Oscar Rausis, David Pitchford, Zhengyang Zhang, Aneesh Batchu, Leslie Liberman, M. Charles Liberman, Christos Constantinidis, Troy Hackett, Ramnarayan Ramachandran