Research reportElectrolytic lesions of the ventral subiculum weakly alter spatial memory but potentiate amphetamine-induced locomotion
Introduction
The subiculum (SUB), the entorhinal cortex (ECx), and the hippocampus proper (HIPP; Cornu ammonis and Gyrus dentatus) form an intimately interconnected complex defined as the hippocampal formation [3], [4]. Briefly, the ECx, a way station for information originating in other rhinal cortical areas (postrhinal cortex, subiculum, presubiculum, etc.), is the major source of HIPP afferents from the neocortex. Visuospatial information is assumed to reach the hippocampus mainly by this way. The fibres from the ECx to the HIPP constitute the perforant paths. Projections to the SUB are an important output from the HIPP [1], [3].
Since the pioneering work by O’Keefe and Nadel [35], the crucial role of the HIPP, and perhaps more generally of the hippocampal formation, in spatial memory functions is documented from both behavioural and electrophysiological viewpoints [25], [33], [40], [43]. Over the past, questions arose as to the role which structures related to the hippocampus proper might play in spatial learning and memory [20], [23], [37]. Many studies dealing with this issue have focussed attention on neurons of the ECx, using conventional or excitotoxic lesion techniques inducing, respectively, important or weak non-specific damage to intrinsic fibres or adjacent regions. The almost consensual picture yielded by these studies was that the induction of major spatial cognition deficits mainly seemed to depend on the extent of non-specific damage: when only neurons of the ECx were damaged, the deficits remained weak or below the sensitivity of many commonly used spatial memory tests [1], [8], [41].
Conversely, behavioural effects of as selective as possible SUB lesions are poorly documented in the literature. This is particularly surprising given the key position of this structure in terms of hippocampal outputs. From this position, one would expect SUB lesions to produce effects similar, at least qualitatively, to those resulting from damage to the hippocampus proper, namely, among the most usual ones, impairments of spatial memory and increased responsiveness to amphetamine. Concerning spatial cognition, Morris et al. [31] found that rats with SUB lesions (and also minimal damage to the dentate gyrus and deep layers of the ECx) were impaired in water-maze acquisition, but acquisition was not prevented and this impairment was not dramatic. Galani et al. [19], [20] showed that rats with selective SUB lesions were slightly but significantly impaired in a working-memory task in the water maze (and a radial maze). Bolhuis et al. [9] reported that SUB and HIPP rats both showed impairments of a preoperatively acquired spatial response in the water maze, but SUB rats were not impaired in relearning another platform location, whereas HIPP ones were.
Concerning its behavioural implication, the HIPP is also considered the source of an inhibitory control of the dopaminergic tonus in the nucleus accumbens [50]. When this inhibitory control is disrupted, for instance by hippocampal ablation or transection of hippocampal connections, rats respond to systemic treatment with the psychostimulant drug amphetamine by an exaggerated locomotor response [7], [15], [42], [49]. To our knowledge, no other experiment than those reported by Caine et al. [13] and Mittleman et al. [30], and which relied on excitotoxic damage to the dorsal or ventral subiculum, has addressed the effects of SUB lesions on the locomotor responsiveness to amphetamine.
Using an electrolysis technique producing almost no hippocampal or ECx damage, the present study examined the effects of ventral SUB lesions on locomotor activity in the home cage and on spatial cognition in either a water-maze task taxing reference or working memory, or a radial-maze task using a protocol that prevented any performance bias by non-spatial egocentric visit strategies. Amphetamine-induced locomotor activity was measured in the home cage. Herein, electrolysis was preferred to a fibre-sparing excitotoxic lesion technique because, based on preliminary experiments of our own, we encountered difficulties in producing an excitotoxic ventral subiculum lesion of sufficient extent, which concomitantly spared all other adjacent regions such as CA1, dentate gyrus or entorhinal as well as perirhinal cortices.
Section snippets
Subjects
All procedures involving animals and their care were conducted in conformity with the guidelines that are in compliance with national (Council directive #87848, 19 October 1987, Ministère de l’Agriculture et de la Forêt, Service Vétérinaire de la Santé et de la Protection Animales; permission #6212 to J.-C.C.; other co-authors under the responsibility of J.-C.C.) and international (NIH publication no. 80-23, revised 1996) laws and policies. All efforts were made to minimise animal suffering and
Extent of the lesions
As shown in Fig. 2, the lesions were confined to the ventral part of the subiculum. They also encroached onto the presubiculum and the parasubiculum. The medial as well as the lateral components of the ECx were intact. In two rats, the lesions encroached slightly onto the most posterior part of the ventral hippocampus, including the largest lesion shown in Fig. 2. From the sections stained for activity of acetylcholinesterase (Fig. 3), obvious signs of reactional septohippocampal and
Discussion
The results of this study demonstrate that lesions restricted to the ventral subiculum may interfere, though rather weakly, with spatial memory capabilities assessed in water-maze and radial-maze tasks. When significant, the effects accounted for slowing down of learning and an impairment of spatial working memory performance in the water maze. In the radial maze, impaired working memory was apparent only during the initial phase of testing. The lesions of the subiculum also potentiated the
Acknowledgements
The authors wholeheartedly acknowledge O. Bildstein, O. Egesi and G. Edomwonyi for their excellent work in animal care.
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