Elsevier

Brain Research Bulletin

Volume 75, Issue 1, 31 January 2008, Pages 119-125
Brain Research Bulletin

Research report
Decreased proportion of GABA neurons accompanies age-related degradation of neuronal function in cat striate cortex

https://doi.org/10.1016/j.brainresbull.2007.08.001Get rights and content

Abstract

Electrophysiological studies indicate that a decline of GABAergic inhibition in the visual cortex may underlie age-related degradation of visual function [A.G. Leventhal, Y. Wang, M. Pu, Y. Zhou, Y. Ma, GABA and its agonists improved visual cortical function in senescent monkeys, Science 300 (2003) 812–815; M.T. Schmolesky, Y. Wang, M. Pu, A.G. Leventhal, Degradation of stimulus selectivity of visual cortical cells in senescent rhesus monkeys, Nat. Neurosci. 3 (2000) 384–390]. To date, there is little direct evidence to support this hypothesis. Using Nissl staining and immunohistochemical techniques, we quantitatively compared the density of total neurons (Nissl-stained neurons) and GABA-immunoreactive neurons as well as the proportion of GABA-immunoreactive neurons to total neurons in the primary visual cortex between 4 young adult (1–3 year old) cats and 4 old (12 year old) cats, which had been previously examined in a single-unit recording study [T. Hua, X. Li, L. He, Y. Zhou, Y. Wang, A.G. Leventhal, Functional degradation of visual cortical cells in old cats, Neurobiol. Aging 27 (2006) 155–162]. In that study, we found the function of V1 (area 17) neurons in the old cats was significantly degraded relative to young adult cats. Our present results indicate that the density of total neurons in each cortical layer of V1 exhibit no significant difference in the two age groups of cats. However, the density of GABA-immunoreactive neurons in old cats is significantly lower than in young adults. Further, the ratio of GABA-immunoreactive neurons to total neurons in each layer of V1 in old cats is also significantly decreased when compared to young adult cats. These results provide direct morphological evidence of decreased GABAergic inhibition in the striate visual cortex of old animals, which accompany the functional degradation of visual cortical neurons.

Introduction

Human visual function degrades with age. As shown in previous psychological experiments, aged humans exhibit decreased visual acuity, binocular summation, contrast sensitivity and wavelength sensitivity [11], [35], [28], [29], [9], [17], [26], [33], [15], [49] as well as poor or slowed performance at tasks requiring orientation discrimination and/or motion direction detection [51], [2], [27], [44], [45]. Most of the age-dependent visual function deterioration cannot be interpreted by changes in the eye [46], [43], [30] and subcortical visual components [41]. Therefore, it is reasonable to assume that a degradation of cortical function in old animals may contribute to those visual capacity declines.

Actually, age-related changes in the function of visual cortical cells have been observed in several species [47], [23], [36], [52], [14], [48]. However, the mechanism underlying these changes is not yet clear. Mendelson and Wells [23] observed a temporal processing decline in the visual cortex of aged rats. They argued that this could be related to cell loss or morphological changes of neurons in the visual cortex. Nevertheless, these general morphological changes cannot appropriately interpret various declines of visual function that accompany old age. Schmolesky et al. [36] suggested that aging results in a decrease in GABAergic inhibition. This could account for the decreased stimulus selectivity of visual cortical neurons they observed in senescent macaque monkeys. Leventhal et al. [19] showed that both GABA and agonists of GABAa receptors significantly improved the function of V1 neurons in old monkeys, while antagonists of GABAa receptors exerted stronger effects in young than in old monkey cortex. Although these results strongly suggest that a weakness of intracortical GABAergic inhibition may underlie visual cortical function degradation during aging, no direct evidence is now available to validate the conclusion.

In a previous study, we comparatively examined the stimulus selectivity and responsiveness of V1 neurons in 4 old (12 years old) and 4 young adult (1–3 years old) cats using extracellular single-unit recording techniques. V1 neurons of old cats exhibited degraded functions as indicated by a lower signal-to-noise ratio, higher spontaneous activity, less selectivity to stimulus orientations and motion directions than do neurons of young adults [14]. Using the same subjects in current study, we compared the density of total neurons and GABA-immunoreactive neurons as well as the ratio of GABA-immunoreactive neurons to total neurons in the primary visual cortex (V1) of old cats with that of young adults, attempting to evaluate whether intracortical GABAergic inhibition in the old brain is reduced or not.

Section snippets

Subjects

The data were acquired from 4 young adult (1–3 years old, male) cats and 4 old (12 years old, male) cats. Each subject was a healthy domestic cat with the history of age and healthcare filed by veterinarians in the Animal hospital and was examined ophthalmoscopically before the experiment to confirm that no optical or retinal problem that would impair their visual function. All animals were treated strictly in accordance with the National Institutes of Health Guide for the Care and Use of

Results

The density of total neurons and GABA-immunoreactive neurons as well as the ratio of GABA neurons to total neurons in each cortical layer of V1 were quantitatively studied in four old cats and four young adult cats. For convenience, subjects studied were named as OC1–4 for old cats 1–4 and YC1–4 for young cats 1–4 (Table 1).

Discussion

Our previous single-unit recording study showed that V1 neurons in the old cats exhibited lower signal-to-noise ratio as well as less selectivity to visual stimulus orientations and motion directions than do cells in the young adults [14]. The functional degradation of visual cortical neurons in old animals was largely attributed to an increase of spontaneous activity and response to all visual stimulations, especially to stimuli with non-optimal orientations and motion directions [36], [14].

Conflict of interest

We declare that what we have done in this research has no conflict of interests with others published in the public journals.

Acknowledgements

We are grateful to Mr. Bo Wen and Mr. Jingwang Xu who contribute a lot to this research in cell counting. This investigation was supported by grants from the National Natural Science Foundation of China (30520120072 to YZ), Foundation of New Century Excellent Talents in University (NCET-04-0586), Specialized Research Fund for the Doctoral Program of Higher Education (20040358046) and Natural Science Foundation of Anhui Province (No. 070413138).

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