AGE-RELATED REDUCTION OF [H-3] STRYCHNINE BINDING-SITES IN THE COCHLEAR NUCLEUS OF THE FISCHER-344 RAT

The present study used quantitative receptor autoradiography to examin e the effects of aging on the binding profile of the strychnine-sensit ive glycine receptor in the Fisher 344 rat. Glycine receptor binding s ites were localized using [H-3]strychnine in two principal subdivision s of the cochlear nucleus; the dorsal and anteroventral cochlear nucle us. These central auditory brainstem structures are known to receive e xtensive glycinergic inputs. In young rats, single concentrations of [ H-3]strychnine showed significantly higher binding levels in the dorsa l cochlear nucleus than the anteroventral cochlear nucleus (+38%, P < 0.001). Little binding was detected in regions of the posteroventral c ochlear nucleus, and no specific binding was apparent in the cerebellu m. Saturation analysis-in the dorsal cochlear nucleus revealed an affi nity constant (K-d) of 16.9 nM and a maximum number of binding sites o f 850 fmol/mg protein. A significant age-related decrease in [H-3]stry chnine (8 nM) binding was observed in the anteroventral cochlear nucle us (-37%, P = 0.003) and dorsal cochlear nucleus (-23%, P = 0.034) of 26-month-old rats compared with three-month-old rats. Saturation analy sis indicated that the observed decrease in binding was due to a decre ase in the total number of binding sites with no significant change in affinity. In the dorsal cochlear nucleus, the number of binding sites was reduced (-26%) in 26-month-old rats compared with three-month-old adults (P = 0.011). K-d was decreased (-22%) in 26-month-old rats whe n compared with young adults, but this decrease was not statistically significant (P = 0.377). The inhibitory neurotransmitter glycine plays an important functional role in the neuronal circuitry of the cochlea r nucleus. These circuits are thought to be involved in echo suppressi on, gain control for coding complex signals, and enhancing the detecti on of signals in noise. Iontophoretic blockade of the inhibitory glyci ne receptor significantly alters these functions. An age-related decre ase in glycinergic neurotransmitter function in the cochlear nucleus c ould result in a decreased ability to process complex acoustic signals , particularly in the presence of background noise.