Effects of brainstem lesions on amino acid levels in the rat cochlear nucleus.

There is evidence for glutamate, γ-amino butyric acid (GABA), and glycine as neurotransmitters of centrifugal pathways to the cochlear nucleus, but the quantitative extent of their contributions to amino acid neurotransmission in cochlear nucleus regions has not been known. We used microdissection of freeze-dried tissue sections of rat cochlear nucleus, with mapping of sample locations, combined with a high performance liquid chromatography (HPLC) assay, to measure amino acid levels in cochlear nucleus subregions of rats with unilateral lesions of centrifugal pathways to the cochlear nucleus. In rats with lesions transecting all or almost all pathways to the cochlear nucleus from brain stem regions, GABA, aspartate, and glutamate levels were reduced, compared to contralateral values, in almost all ipsilateral cochlear nucleus regions. The largest reductions, in dorsal (DCN), anteroventral (AVCN), and posteroventral (PVCN) cochlear nucleus regions, approached 50% for GABA, 40% for aspartate, and 30% for glutamate. In contrast, glutamine and taurine levels were typically higher in lesioned-side cochlear nucleus regions than contralaterally. Effects on glycine levels were mixed but usually included increased lesioned-side values compared to contralateral, probably reflecting a balance between increases during protein breakdown and decreases of free glycine in transected pathways. More limited lesions transecting just dorsal pathways showed much less effect on amino acid levels. Lesion of the ipsilateral trapezoid body connection plus ipsilateral superior olivary nuclei resulted in decreases of GABA, aspartate, and glutamate levels especially in ventral cochlear nucleus regions. No clear contralateral effects of this lesion could be shown. The results most strongly support centrifugal GABAergic pathways to the cochlear nucleus, providing almost half of GABAergic neurotransmission in most regions. Our results support and extend previously published measurements of lesion effects on GABA uptake and release in cochlear nucleus subdivisions.

Amino acid and acetylcholine chemistry in mountain beaver cochlear nucleus and comparisons to pocket gopher, other rodents, and cat.

The mountain beaver and pocket gopher are two rodents that live mostly underground in tunnel systems. Previous studies have suggested that their cochlear nucleus structure, particularly that of the dorsal cochlear nucleus (DCN), differs significantly from that of other mammals, that the hearing ability of the pocket gopher is deficient compared to that of other rodents, and that the DCN of the mountain beaver is more responsive to slow oscillations of air pressure than to sounds. We conducted some electrophysiological recordings from mountain beaver DCN and then used microchemical methods to map in mountain beaver cochlear nuclei the distributions of amino acids, including the major neurotransmitters of the brain, and enzyme activities related to the metabolism of the neurotransmitter acetylcholine, which functions in centrifugal pathways to the cochlear nucleus. Similar measurements were made for a pocket gopher cochlear nucleus. Responses to tonal stimuli were found in mountain beaver DCN. Distributions and magnitudes of neurotransmitter and related amino acids within mountain beaver and pocket gopher cochlear nuclei were not very different from those of other rodents and cat. However, the enzyme of synthesis for acetylcholine, choline acetyltransferase, had only low activities in the DCN of both mountain beaver and pocket gopher. The chemical distributions in the mountain beaver DCN support a conclusion that it corresponds to just the superficial DCN portion of other mammals. High correlations between the concentrations of γ-aminobutyrate (GABA) and glycine were found for both mountain beaver and pocket gopher cochlear nuclei, suggesting that their co-localization in cochlear nucleus synapses may be especially prominent in these animals. Previous evidence suggests convergence of somatosensory and auditory information in the DCN, and this may be especially true in animals spending most of their time underground. Our results suggest that the enlarged DCN of the mountain beaver and that of the pocket gopher are not very different from those of other rodents with respect to involvement of amino acid neurotransmitters, but they appear to have reduced cholinergic innervation.

Changes of amino acid concentrations in the rat vestibular nuclei after inferior cerebellar peduncle transection.

Although there is a close relationship between the vestibular nuclear complex (VNC) and the cerebellum, little is known about the contribution of cerebellar inputs to amino acid neurotransmission in the VNC. Microdissection of freeze-dried brain sections and high-performance liquid chromatography (HPLC) were combined to measure changes of amino acid concentrations within the VNC of rats following transection of the cerebellovestibular connections in the inferior cerebellar peduncle. Distributions of 12 amino acids within the VNC at 2, 4, 7, and 30 days after surgery were compared with those for control and sham-lesioned rats. Concentrations of gamma-aminobutyric acid (GABA) decreased by 2 days after unilateral peduncle transection in nearly all VNC regions on the lesioned side and to lesser extents on the unlesioned side and showed partial recovery up to 30 days postsurgery. Asymmetries between the two sides of the VNC were maintained through 30 days. Glutamate concentrations were reduced bilaterally in virtually all regions of the VNC by 2 days and showed complete recovery in most VNC regions by 30 days. Glutamine concentrations increased, starting 2 days after surgery, especially on the lesioned side, so that there was asymmetry generally opposite that of glutamate. Concentrations of taurine, aspartate, and glycine also underwent partially reversible changes after peduncle transection. The results suggest that GABA and glutamate are prominent neurotransmitters in bilateral projections from the cerebellum to the VNC and that amino acid metabolism in the VNC is strongly influenced by its cerebellar connections.