Research reportRetinal lesions affect extracellular glutamate levels in sensory-deprived and remote non-deprived regions of cat area 17 as revealed by in vivo microdialysis
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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- 1
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.