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 examine the effects of aging on the binding profile of the strychnine-sensitive glycine receptor in the Fisher 344 rat. Glycine receptor binding sites were localized using [H-3]strychnine in two principal subdivisions of the cochlear nucleus; the dorsal and anteroventral cochlear nucleus. These central auditory brainstem structures are known to receive extensive glycinergic inputs. In young rats, single concentrations of [H-3]strychnine showed significantly higher binding levels in the dorsal cochlear nucleus than the anteroventral cochlear nucleus (+38%, P < 0.001). Little binding was detected in regions of the posteroventral cochlear nucleus, and no specific binding was apparent in the cerebellum. Saturation analysis-in the dorsal cochlear nucleus revealed an affinity constant (K-d) of 16.9 nM and a maximum number of binding sites of 850 fmol/mg protein. A significant age-related decrease in [H-3]strychnine (8 nM) binding was observed in the anteroventral cochlear nucleus (-37%, P = 0.003) and dorsal cochlear nucleus (-23%, P = 0.034) of 26-month-old rats compared with three-month-old rats. Saturation analysis indicated that the observed decrease in binding was due to a decrease 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 when 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 cochlear nucleus. These circuits are thought to be involved in echo suppression, gain control for coding complex signals, and enhancing the detection of signals in noise. Iontophoretic blockade of the inhibitory glycine receptor significantly alters these functions. An age-related decrease in glycinergic neurotransmitter function in the cochlear nucleus could result in a decreased ability to process complex acoustic signals, particularly in the presence of background noise.