Journal of Neuroscience, Vol 10, 2363-2372, Copyright © 1990 by Society for Neuroscience
Immunocytochemical and neurochemical evidence for age-related loss of GABA in the inferior colliculus: implications for neural presbycusis
DM Caspary, A Raza, BA Lawhorn Armour, J Pippin and SP Arneric
Southern Illinois University School of Medicine, Springfield 62794-9230.
The present study describes substantial, selective, age-related loss of the
putative inhibitory neurotransmitter GABA in the central nucleus of the
inferior colliculus (CIC) of rat based on immunocytochemical and
neurochemical data. For immunocytochemistry, neurons in the CIC were
immunolabeled using an antibody against a GABA conjugate in young adult (2-
to 7-month-old) and aged (18- to 29-month-old) Fischer-344 rats.
Computer-assisted morphometry was then used to generate maps of GABA-
immunoreactive neurons in the CIC. The number of GABA-positive neurons was
reduced 36% in the ventrolateral portion of the CIC of aged animals (93
neurons/mm2) compared to their matched young adult cohorts (145
neurons/mm2; p less than 0.01). For neurochemistry, basal and K(+)- evoked
release of the endogenous amino acids GABA, glutamate (Glu), aspartate
(Asp), and tyrosine (Tyr) from micropunches of the CIC were measured in 8
age-paired animals from the 2 age groups using high- performance liquid
chromatography. Overflow of radiolabeled acetylcholine (3H-ACh) was also
determined. In both age groups, K(+)- evoked release of GABA, Glu, Asp, and
3H-ACh from CIC punches was significantly enhanced above basal efflux
(+200, +215, +163, and +309%, respectively), while Tyr release was
unchanged. Evoked release of 3H- ACh and all amino acids except Tyr showed
substantial Ca2+ dependence. A significant (p less than 0.05) age-related
reduction in both basal (- 35%) and K(+)-stimulated (-42%) efflux of GABA
from the CIC was observed. A corresponding decrease in postrelease tissue
content of GABA in CIC of aged rats was observed (-30%, p less than 0.05).
In contrast, tissue content as well as basal and evoked release of Glu,
Asp, Tyr, and 3H-ACh was similar between the 2 age groups. Age-related GABA
neurochemical changes described in the CIC were not observed in the release
of the other amino acids or 3H-ACh from either the rostral ventrolateral
medulla or the somatosensory cortex, 2 brain regions involved in processing
non-auditory sensory input. These data support previous findings that GABA,
Glu, Asp, and ACh may subserve neurotransmission in the CIC. Additionally,
these data provide clear evidence for a pronounced, region- and
neurotransmitter-selective, age- related reduction of GABA in the CIC.
These findings support the hypothesis that impairment of inhibitory
GABAergic neurotransmission in the CIC may contribute to abnormal auditory
perception and processing seen in neural presbycusis.
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