AMPA receptor binding in adult guinea pig brain stem auditory nuclei after unilateral cochlear ablation

This study determined if an asymmetric hearing loss, due to unilateral cochlear ablation, could induce the regulation of intracellular AMPA receptors in brain stem auditory nuclei. In young adult guinea pigs, the high-affinity specific binding of [(3)H]AMPA was measured in the cochlear nucleus (CN), the superior olivary complex (SOC), and the auditory midbrain at 2-147 postlesion days. After correction for tissue shrinkage, changes in specific binding relative to that in age-matched unlesioned controls were interpreted as altered numbers and/or activity of intracellular AMPA receptors. In the CN, transient elevations and/or deficits in binding were evident in most regions, which usually recovered by 147 days. However, persistently deficient binding was evident ipsilaterally in the anterior part of the anteroventral CN (AVCNa). In the SOC, transient elevations in binding were evident at 2 days in the medial limb of the lateral superior olive (LSOmed) and the medial superior olive. Between 7 and 147 days, most SOC nuclei exhibited transient, temporally synchronized postlesion deficits in binding. However, late in the survival period, deficits persisted ipsilaterally in the LSOmed and the lateral (LSOlat) limb of the lateral superior olive. In the midbrain, transient elevations and/or deficits in binding were evident in the dorsal nucleus of the lateral lemniscus as well as in the central and dorsal nucleus of the inferior colliculus. A persistent deficit was evident in the intermediate nucleus of the lateral lemniscus. The findings implied that auditory neurons contain regulatory mechanisms that control the numbers and/or activity of intracellular AMPA receptors. Regulation was induced by cochlear nerve destruction and probably by changes in the excitation of glutamatergic neurons. Many of the regulatory changes were transient, except in the ipsilateral AVCNa and LSO, where postlesion downregulations were persistent. The downregulation in the ipsilateral AVCNa was probably induced directly by the loss of cochlear nerve endings. However, other regulatory changes may have been induced by signals carried on pathways emerging from the ipsilateral CN and on centrifugal auditory pathways.