Distribution and Targeting of Glutamate Receptors in the Cochlear Nucleus

Abstract

Glutamate (or a related excitatory amino acid) is a major excitatory neurotransmitter in the mammalian cochlear nucleus (for reviews, see Wenthold. 1991; Hunter et al., 1992; Wenthold et al., 1993). Two main excitatory pathways which terminate in the cochlear nucleus, the auditory nerve and the parallel fiber pathway, both use glutamate as a neurotransmitter, and, although the evidence is less compelling, most other excitatory synapses in the cochlear nucleus probably also use glutamate as a neurotransmitter. The dominant role of glutamate in the cochlear nucleus is consistent with its role elsewhere in the CNS where it is thought to be a neurotransmitter at most excitatory synapses (Monaghan et al., 1989). In addition to this major role in neurotransmission, two other properties have also contributed to the intense interest in glutamate: 1) Glutamate and glutamate analogs are potent neurotoxins, and this neurotoxicity is mediated through the same receptors which are involved in neurotransmission (for review, see Choi and Rothman, 1990). Human disorders, such as stroke, may involve a release of glutamate which leads to further neuronal loss through excitotoxicity. Therefore, blocking glutamate receptors would be expected to lessen the damage, and animal studies have indicated this may be a promising approach to treatment. Furthermore, neuronal loss that occurs with some neurodegenerative disorders may involve excitotoxicity suggesting that a similar treatment may be promising. 2) Glutamate receptors are involved in synaptic plasticity such as in learning and memory or synapse formation. In one model it is proposed that long-term potentiation (LTP) results from an increase in functional AMPA receptors at the postsynaptic membrane (Liao et al., 1995). Therefore, knowledge of the mechanisms which regulate the expression of synaptic glutamate receptors will give insights into the general area of synaptic plasticity.