Elsevier

Brain Research

Volume 962, Issues 1–2, 7 February 2003, Pages 199-206
Brain Research

Research report
Retinal lesions affect extracellular glutamate levels in sensory-deprived and remote non-deprived regions of cat area 17 as revealed by in vivo microdialysis

https://doi.org/10.1016/S0006-8993(02)04047-7Get rights and content

Abstract

This study aimed at gaining insight into the role of the excitatory neurotransmitter glutamate in topographic map reorganization in the sensory systems of adult mammals after restricted deafferentations. Hereto, in vivo microdialysis was used to sample extracellular glutamate from sensory-deprived and non-deprived visual cortex of adult awake cats 18 to 53 days after the induction of restricted binocular retinal lesions, and in topographically corresponding cortical regions of control animals. A microbore HPLC-ED method was applied for the analysis of the microdialysates. In normal subjects, the visual cortex subserving central and peripheral vision showed similar extracellular fluid glutamate concentrations. In contrast, in animals with homonymous central retinal lesions, the extracellular glutamate concentration was significantly lower in central, sensory-deprived cortex compared to peripheral, non-deprived cortex. Compared to control regions in normal subjects, glutamate decreased in the extracellular fluid of deprived cortex but increased significantly in remote non-deprived visual cortex. These results not only suggest an activity-dependent regulation of the glutamate levels in visual cortex but also imply a role for perilesional cortical regions in topographic map reorganization following sensory deafferentation.

Introduction

In the visual system of adult cats and monkeys, binocular retinal lesions produce a sensory-deprived zone in the corresponding region of the primary visual cortex in which neurons no longer respond to visual stimuli. Within a few months, the cells in the lesion-affected cortical area regain responsiveness to visual stimulation through the acquisition of new receptive fields receiving inputs from retinal locations adjacent to the lesions [6], [13], [14], [16]. Proposed structural mechanisms for such a reorganization of cortical topography include alterations in the effectiveness of previously existing connections and the growth of new connections. However, the molecular mechanisms underlying this reorganization of the adult brain are poorly understood.

Several neurotransmitters and neuromodulators have already been implicated in adult brain plasticity [1], [3], [4], [5], [7], [18], [26], [33]. Indeed, the involvement of the major inhibitory neurotransmitter gamma-amino-butyric acid in cortical reorganization has been demonstrated in visual and somatosensory cortex using immunocytochemical methods [12], [33]. The same holds for the excitatory neurotransmitter of the mammalian cerebral cortex, glutamate [7], [9], [21], [40]. The changes in glutamate immunoreactivity in sensory-deprived area 17 of adult retinal lesion cats have been correlated with changes in synaptic efficacy based on the accompanying changes in spontaneous and visually evoked activity [2], [8]. Together these findings support the belief that activity-dependent changes in the balance between excitation and inhibition would foster the plasticity underlying topographic map reorganization [15].

Despite the significant number of immunocytochemical reports on decreased and increased neurotransmitter and neuromodulator levels during cortical reorganization, we have no clue on how these differences are generated. Indeed, whether these result from changes in their synthesis, presynaptic release, re-uptake or break down remains an open question. A better understanding of the contribution of each of these cellular mechanisms can only be achieved through the refinement of our knowledge, i.e. by assessing parallel fluctuations in the extracellular fluid concentrations for these neurotransmitters and modulators. We therefore developed an in vivo microdialysis–HPLC method applicable to cat neocortex [25], [27], [28]. Here, we investigated the influence of binocular retinal lesions on the extracellular glutamate concentration in the visual cortex of awake adult cats. We present evidence for changes in extracellular glutamate throughout the visual cortex of retinal lesion cats, including sensory-deprived and remote non-deprived cortical regions and in comparison to normal control subjects.

These results have been partially published in abstract form [24].

Section snippets

Animals

All animal experiments were approved by the institutional Ethical Committee of the Katholieke Universiteit Leuven and were carried out in accordance with the European Communities Council Directive of 24 November 1986 (86/609/EEC). All efforts were made to minimize animal suffering and to reduce the number of animals used.

Fourteen adult cats (Animal Facilities, Katholieke Universiteit Leuven, Belgium) of both sexes (weight 2.5–5 kg) were used. Five served as normal controls, nine received

Histological and immunocytochemical control of probe implantation

Nissl staining of vibratome sections at the level of the probe guides and cannulae revealed that all the microdialysis probes from which we collected data for this study were implanted in the grey matter of area 17 (Fig. 1A). The impact of probe guide implantation onto surrounding tissue was minimal since immunocytochemistry for glial fibrillary acid protein (GFAP) only revealed a small increase in the number of GFAP-stained cells in the vicinity of the microdialysis track thereby excluding

Discussion

This study demonstrates that the levels of the excitatory amino acid glutamate are significantly higher in remote, non-deprived cortical regions compared to the sensory-deprived visual cortex of animals with homonymous central retinal lesions as well as to topographically matched cortical regions of normal animals. This alteration in the extracellular excitatory amino acid concentration correlates with the topographic map reorganization generated in visual cortex by retinal lesions as revealed

Acknowledgements

We are grateful to Ria Vanlaer for valuable technical assistance. This work was supported by grants from the Queen Elisabeth Medical Foundation, the Research Fund of the K.U.Leuven and the Fund for Scientific Research—Flanders, Belgium. Lutgarde Arckens was supported as a postdoctoral fellow and Ann Massie as a research assistant of the Fund for Scientific Research—Flanders, and Estelle Van der Gucht as a postdoctoral fellow of the Research Fund of the K.U.Leuven.

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    Present address: Section of Brain Physiology and Metabolism, National Institute on Aging, NIH, Building 10, Room 6N202, Bethesda, MD 20892, USA. Tel.: +1-301-594-3134; fax: +1-301-402-0074.

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