Synaptic nests lack glutamate transporters in the cochlear nucleus of the mouse

Synaptic nests are closely packed collections of synaptic endings. Nests may be deficient in the glial processes which usually separate terminals in the CNS and which transport much of the glutamate associated with high levels of excitatory activity. We hypothesized that nests might lack glial glutamate transporters, but possibly would conserve neuronal glutamate transporter. Although present throughout the brain, nests are especially numerous in the cochlear nucleus. We performed immunoelectron microscopy by preembedding peroxidase and immunogold methods and by postembedding immunogold to detect expression of the glutamate transporters GLAST, GLT-1, and EAAC1 in the mouse cochlear nucleus. Our results show that the glial transporters, GLAST and GLT-1, are absent in synaptic nests. This deficiency is not compensated by the neuronal transporter EAAC1, which is poorly represented in nests. Outside synaptic nests, all three glutamate transporters are strongly expressed in the cochlear nucleus. Thus, glutamate released outside nests should be quickly bound by transporters and removed from the extracellular glutamate pool. Glutamate released within synaptic nests may persist long enough to permit diffusion to extrajunctional targets in the nest, including presynaptic receptors. Consequently, synaptic nests may play a role in modulation of synaptic activity but also in excitotoxic mechanisms.