Elsevier

Brain Research

Volume 800, Issue 1, 27 July 1998, Pages 40-47
Brain Research

Research report
Forebrain contribution to the induction of a brainstem correlate of conditioned taste aversion: II. Insular (gustatory) cortex

https://doi.org/10.1016/S0006-8993(98)00492-2Get rights and content

Abstract

The induction of c-Fos-like immunoreactivity (c-FLI) in the intermediate division of the nucleus of the solitary tract (iNTS) has been shown to be a cellular correlate of the behavioral expression of a conditioned taste aversion (CTA). To further define neuroanatomical structures and pathways that contribute to this cellular response and to CTA learning in general, electrolytic lesions of insular (gustatory) cortex (IC) were combined with immunostaining for c-FLI. Rats were given either unilateral or bilateral electrolytic lesions of insular cortex or `sham' operations. Following surgery, `paired' animals were given a single conditioning trial consisting of intraoral infusion of 5-ml 0.15% sodium–saccharin followed by injection with LiCl (0.15 M, 20 ml/kg, i.p.) while `unpaired' controls received a non-contingent saccharin–LiCl presentation. Rats with bilateral lesions showed no behavioral evidence of having acquired a CTA. Increases in c-FLI in iNTS were evident, but reduced, relative to `sham' animals. Rats with unilateral-lesions displayed a CTA by rejecting the saccharin, although increases in c-FLI on the side of the iNTS ipsilateral to the lesion were reduced relative to that seen in `sham' animals. A comparison of these results with those obtained after amygdala lesions supports the conclusion that amygdala and insular cortex are necessary, but not sufficient, for the behavioral expression of a CTA.

Introduction

Taste aversion learning is a robust form of classical conditioning in which animals come to avoid a taste (CS, conditioned stimulus) that has previously been paired with a treatment (US, unconditioned stimulus) that produces transient illness 2, 7. The induction of c-Fos-like immunoreactivity (c-FLI) in the intermediate division of the nucleus of the solitary tract (iNTS) has been demonstrated to be a cellular correlate of the behavioral expression of a conditioned taste aversion (CTA) 8, 22, 23. Exposure to a taste CS (saccharin) that has been paired with LiCl (US) induces significant c-FLI in the medial subnucleus of iNTS 22, 23, a response that is not evident in control animals exposed to saccharin unpaired with LiCl, nor to an innately aversive taste, quinine [24].

We have been using immunostaining for c-FLI in combination with conventional lesion methodologies to define specific neural pathways involved in CTA learning. We recently demonstrated that bilateral electrolytic lesions of the amygdala eliminate both the behavioral expression of a CTA and accompanying c-FLI in iNTS [21]. Rats with bilateral lesions of amygdala showed no evidence of having acquired a CTA and no increases in c-FLI in iNTS relative to unpaired controls. In contrast, rats with unilateral amygdala lesions acquired a CTA but showed increases in c-FLI only on the side of iNTS contralateral to the lesion. These findings were interpreted to suggest that a lateralized connection between amygdala and iNTS is necessary for retrieval or behavioral expression of a CTA.

Because those studies employed electrolytic lesions of the amygdala, the possibility remained that the dramatic effects on both c-FLI and behavior were actually due to damage to fibers originating in structures anterior to the amygdala which project to NTS [5]. One structure that has figured prominently in the CTA literature is the insular cortex (IC), particularly the agranular region, which is the recipient of gustatory information 14, 18, 19and which projects extensively to regions of the NTS involved in gustatory and autonomic function [12]. Lesions of IC, both electrolytic and excitotoxic, have been shown to attenuate CTA learning 1, 5, 9, 10, 11, 27. The purpose of the present study was twofold: to evaluate the role of IC in both CTA learning and the induction of c-FLI in iNTS and to assess whether the effects of amygdala lesions in our previous studies [21]could have been due to damage to pathways from IC. To do this the present study combined lesions of IC with immunostaining for c-FLI. Unilateral lesions addressed the question of whether a localized lesion of IC would produce a pattern of c-FLI in iNTS similar to that seen in unilateral amygdala-lesioned animals. Bilateral lesions permitted an assessment of the contribution of IC to behavioral indices of CTA learning.

Section snippets

Subjects

Subjects consisted of 21 adult male Long–Evans rats obtained from the breeding colony at the University of Washington. At the time of surgery, free-feeding body weights ranged between 300 to 400 g. Rats were housed individually in suspended stainless steel cages and maintained on a 12:12 h light/dark cycle. Teklad rodent chow and water were provided ad libitum.

Surgery

Under Equithesin (3.3 mg/kg) anesthesia, rats were first implanted with bilateral intraoral cannulae and then given either unilateral or

Behavioral data

Behavioral reactions to the intraoral infusion of the saccharin CS are depicted in Fig. 1. The bilaterally-lesioned, unpaired group (IC-Bilat-UnP) represents the unconditioned control group in this study. It is evident from the figure that rats in this group ingested the saccharin throughout the 10-min infusion period, a finding which is virtually identical to that of previous studies in our laboratory which have utilized unpaired control groups without lesions 22, 23, 24. Consistent with our

Discussion

Previous studies have demonstrated that the induction of c-FLI in iNTS is a reliable cellular correlate of the behavioral expression of a CTA 8, 22, 23. Neural connections between iNTS and the forebrain are necessary for this response [22]and electrolytic lesions of the amygdala eliminate this response as well as the behavioral expression of a CTA [21]. IC, like amygdala, is a major source of efferents projecting to iNTS [20]. Further, it has been suggested that electrolytic lesions of amygdala

Acknowledgements

This research was supported by NIH Grant DC00248 and a Royalty Research Grant from the University of Washington.

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