Behavioural Brain Research 112 (2000) 69 – 75 Research report Lesions of the perirhinal cortex impair sensory preconditioning in rats Daniel A. Nicholson, John H. Freeman Jr. * Department of Psychology, Uniersity of Iowa, Seashore Hall, Iowa City, IA 52242, USA Received 12 October 1999; received in revised form 1 February 2000; accepted 2 February 2000 Abstract The effects of lesions of the perirhinal cortex on the development of associations between two conditioned stimuli (CSs) were examined with a sensory preconditioning procedure. Rats were given either bilateral electrolytic lesions of the perirhinal cortex or control surgery. They were then given either paired or unpaired presentations of a light CS and a tone CS. All of the rats were then given eyeblink conditioning procedures that involved paired presentations of either the light or tone and a periorbital shock unconditioned stimulus (US). The rats were finally given a test session that consisted of unpaired presentations of the tone and light CSs. Sensory preconditioning was established in the control group, but not in the lesion group. The findings are consistent with the view that the perirhinal cortex is involved in forming associations between neutral stimuli (even in the absence of reinforcement). © 2000 Elsevier Science B.V. All rights reserved. Keywords: Rhinal; Learning; Eye-blink; Perirhinal; Conditioning; Associative www.elsevier.com/locate/bbr 1. Introduction A great deal of progress has been made toward understanding the neurobiology of simple associative learning [1,9,11,16,19,24 – 26,29,39,42,49]. Classical con- ditioning procedures can be used to establish simple associative learning by pairing a conditioned stimulus (CS) with an unconditioned stimulus (US). Sensory preconditioning is a special case of simple associative learning because it involves an initial pairing of two conditioned stimuli (CS1 and CS2 in phase 1) in the absence of an unconditioned stimulus, after which the subject is trained in traditional classical conditioning (CS1-US in phase 2) [5]. The presence of an association between CS1 and CS2 can only be inferred by post- training test presentations of CS2 (phase 3). Previous studies have shown that animals given initial CS1-CS2 pairings before CS1-US training respond to test presen- tations of CS2, whereas control groups given unpaired presentations of CS1 and CS2 do not [36,37,47,48]. It is thought that the animals given paired training respond to CS2 by virtue of its association with the excitatory CS1 [5,48]. The two conditioned stimuli often differ in modality (e.g. tone and light) and thus require the formation of a crossmodal association. It is difficult to specifically distinguish between dis- ruptions of encoding or retrieval because of their inti- mate relationship [38,50]. However, the clearly delineated encoding and retrieval opportunities for a CS1-CS2 association in sensory preconditioning (i.e. phase 1 and phase 3, respectively) enable a more fo- cused study of the underlying neural bases of sensory associations. Previous studies of the neural mechanisms of sensory preconditioning demonstrated that lesions of non-spe- cific association cortex [47], the fimbria [36], or field CA1 of the hippocampus [37] prevented the establish- ment of sensory preconditioning. Based on these stud- ies, a reasonable conclusion is that the connectivity between the hippocampus and cerebral cortex must * Corresponding author. Tel.: +1-319-3353243; fax: +1-319- 3350191. E-mail address: john-freeman@uiowa.edu (J.H. Freeman Jr.) 0166-4328/00/$ - see front matter © 2000 Elsevier Science B.V. All rights reserved. PII:S0166-4328(00)00168-6