Lesions of the Cerebral Cortex and Caudate‐Putamen Enhance GABA Function in the Rat Superior Colliculus

Abstract

Unilateral lesions of the rat frontal cortex were made either alone or in combination with the caudate-putamen in order to examine (a) their morphological influence on the substantia nigra and (b) their neurochemical influence on GABA function in the superior colliculus. One to two months following the combined lesion, neuronal somata in the ipsilateral pars reticulata of the substantia nigra were clearly hypertrophied (+ 30%). Morphological changes in the substantia nigra were not evident contralaterally or in animals bearing only cortical lesions. One to two months following cortex-only lesions, no significant alterations in tectal GABA concentration were observed. However, the combined lesion induced elevations of GABA within both the medial and lateral sectors of the intermediate and deep layers of the superior colliculus. This effect was restricted to the ipsilateral side and was most pronounced in lateral sectors. The vast majority of GABA released from superfused control tectal slices by a depolarizing stimulus (35 mM KCl) was calcium-dependent. Such evoked GABA release from ipsilateral tectal slices was significantly reduced (- 25%) by unilateral lesions of the substantia nigra, a structure that is known to provide GABA-containing inputs to the tectum. In contrast, cortical lesions alone significantly enhanced the evoked tectal GABA release (+ 66%), although their influence was again confined to the ipsilateral side. Combined lesions of the cerebral cortex and caudate-putamen significantly enhanced the evoked GABA release from tectal slices in both hemispheres but the changes were most marked ipsilaterally (+ 147%). It is suggested that the hypertrophy of GABA-containing nigrotectal somata seen after removal of corticostriatal, corticotectal and in particular GABA-containing striatonigral fibres may reflect concomitant increases in GABA synthesis within and/or sprouting of nigrotectal terminals.

Neuronal hypertrophy in the pars reticulata of the substantia nigra in Parkinson's disease

“…More recent studies have shown that this hypertrophy is accompanied by an increase in K+-stimulated, Na+ +-dependent yaminobutyric acid release from, and content in, the superior colliculus (Kilpatrick et al, 1988(Kilpatrick et al, . 1989(Kilpatrick et al, , 1990, and by increased levels of specific mRNAs within the enlarging neurons, including those encoding the y-aminobutyric acid (GABA) synthesizing enzyme, glutamic acid decarboxylase (Lindefors, Brene & Persson, 1990;Najlerahim et al, 1990), and the structural protein, a , tubulin (Najlerahim et al, 1990).…”

“…These data have been interpreted as indicating sprouting of y-aminobutyric acid-using axons originating from the pars reticulata, accompanying degeneration of the dopaminergic pars compacta, and resulting in increased inhibitory input to the superior colliculus and Note: Case 11 had mixed Alzheimer's disease/Parkinson's disease pathology; case 1 died of a paracetamol overdose; case 2 died of haemorrhage during an operation to replace a diseased heart valve. PMI, post-mortem interval in hours; PD, Parkinson's disease; AD, Alzheimer's disease thalamus (Pearson et al, 1986(Pearson et al, , 1987Kilpatrick et al, 1990). It has been proposed (Pearson et al, 1987) that similar events, if they occur in Parkinson's disease, might account for some of the later symptoms of the disease and, in part, for the late failure of dopaminergic therapy (Bonnet et al, 1987).…”