Elsevier

Neuroscience

Volume 91, Issue 4, July 1999, Pages 1355-1368
Neuroscience

The effects of radiofrequency lesion or transection of the fimbria–fornix on latent inhibition in the rat

https://doi.org/10.1016/S0306-4522(98)00691-5Get rights and content

Abstract

Latent inhibition consists of a decrement in conditioning to a stimulus as a result of its prior non-reinforced pre-exposure. Based on evidence pointing to the involvement of the hippocampus and the nucleus accumbens in latent inhibition disruption, it has been proposed that latent inhibition depends on the integrity of the subicular input to the nucleus accumbens. Since fibers originating in the subiculum and destined for the nucleus accumbens run through the fimbria–fornix, we assessed the effects of radiofrequency lesion or transection of the fimbria–fornix, on latent inhibition. The effectiveness of both lesions was demonstrated by the total disappearance of acetylcholinesterase staining in the hippocampus and of retrogradely labeled cells in the hippocampus/subiculum following the injection of the retrograde tracer biotin–dextran amine into the shell subregion of the nucleus accumbens. Likewise, in accord with previously documented behavioral effects of lesions to the hippocampus and related structures, both lesions increased spontaneous activity and disrupted performance in Morris water maze, and the radiofrequency lesion facilitated the acquisition of two-way active avoidance. In spite of the above, latent inhibition remained unaffected by both fimbria–fornix lesions, indicating that the critical projections subserving latent inhibition are not those traversing the fimbria–fornix from the hippocampus/subiculum to the nucleus accumbens.

The implications of these results for the neural circuitry of latent inhibition and the latent inhibition model of schizophrenia are discussed.

Section snippets

Subjects

Male Wistar rats (Zur:WIST[HanIbm] Institute of Toxicology, Schwerzenbach, Switzerland), approximately two months old and weighing approximately 300 g, were housed four to a cage under a reversed light–dark cycle (lights on: 19.00–07.00) with free access to food and water, except for Experiment 1 (see below). Seventy-two rats were used for the fimbria–fornix transection (FFT) and 60 rats for the fimbria–fornix radiofrequency lesion (RFL). Each cohort of animals was divided randomly into three

Biotin–dextran amine retrograde tracing

The locations of the injections in the shell of the NAC were typically slightly more medial than expected from the coordinates of the Paxinos and Watson atlas.65 In some animals, BDA had spilled into the septum and/or cingulate cortex areas 1 and 2, and frontal cortex area 2. More specifically, of the 37 brains assessed, 18 had injections restricted to the shell, five had a trace of BDA in the cortex, six had a trace in the cortex and septum, five had a trace in the septum, and two displayed no

Discussion

The effectiveness of both the transection and the radiofrequency lesion of the fimbria–fornix used here was confirmed by histological and behavioral results. Thus, the completeness of the lesions was ascertained using Cresyl Violet and Gallyas stains of the fimbria–fornix, and only the behavioral data of rats which sustained a complete lesion were included in the analysis of the behavioral effects of both lesions. The conclusions about the completeness of the lesions, as observed with

Conclusions

The effects of lesions to different regions of the hippocampal formation and the fimbria–fornix are of particular interest given the fact that disrupted LI is considered to provide an animal model of schizophrenia. There is increasing evidence that pathology in temporolimbic structures is an essential feature of schizophrenia (e.g., see 5., 6., 8., 10., 14.), and this pathology has been suggested to underlie LI disruption observed in schizophrenic patients.25., 91. However, the fact that LI is

Acknowledgements

This work was supported by grants from the Swiss National Science Foundation and the Swiss Federal Institute of Technology, Zurich. The authors thank the animal facility team of Dr Allmann for their care of the animals, Ms Liz Weber for her histological preparations and Ms Bonnie Strehler for her assistance with manuscript preparation.

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