Neurobiology of Learning and Memory 87 (2007) 133–139 www.elsevier.com/locate/ynlme 1074-7427/$ - see front matter  2006 Elsevier Inc. All rights reserved. doi:10.1016/j.nlm.2006.07.006 Substantia nigra role in fear conditioning consolidation Elisabetta Baldi, Chiara Mariottini, Corrado Bucherelli ¤ Department of Physiological Sciences, University of Florence, Viale G.B. Morgagni 63, I-50134, Florence, Italy Received 9 May 2006; revised 5 July 2006; accepted 24 July 2006 Available online 15 September 2006 Abstract The substantia nigra (SN) is known to be involved in the memorization of several conditioned responses. To investigate the role of the SN in fear conditioning consolidation this neural site was subjected to fully reversible tetrodotoxin (TTX) inactivation during consolida- tion in adult male Wistar rats which had undergone fear training to acoustic CS and context. TTX was stereotaxically administered to diVerent groups of rats at increasing intervals after the acquisition session. Memory was assessed as conditioned freezing duration mea- sured during retention testing, always performed 72 and 96 h after TTX administration. In this way there was no interference with normal SN function during either acquisition or retrieval phases, so that any amnesic eVect could be due only to consolidation disruption. The results show that SN functional integrity is necessary for contextual fear response consolidation up to the 24-h after-acquisition delay. On the contrary SN functional integrity was shown not to be necessary for the consolidation of acoustic CS fear responses. The present Wnd- ings help to elucidate the role of the SN in memory consolidation and better deWne the neural circuits involved in fear memories.  2006 Elsevier Inc. All rights reserved. Keywords: Context; Functional inactivation; Aversive responses; Nigrostriatal dopaminergic system 1. Introduction The substantia nigra (SN) is a reticulated structure located in the brain stem. It is a section of a larger mesote- lencephalic system with perikarya in ventral midbrain and projections to striatum, pallidum, basal forebrain, limbic structures and cerebral cortex (Moore & Bloom, 1978). It is well known that the nigrostriatal dopaminergic system exerts a critical inXuence on the responses of tonically active striatal neurons related to the control of fear, emo- tions, learning and memory. In particular, the SN is a key structure involved in diverse kinds of learning as spatial memory (Levin, Briggs, Christopher, & Auman, 1994; Miyoshi et al., 2002), rewarded operant conditioning (Cor- rea, Mingote, Betz, Wisniecki, & Salamone, 2003; Dowd & Dunnett, 2005; Gulley, Kosobud, & Rebec, 2002; Trevitt, Carlson, Nowend, & Salamone, 2001) and aversive condi- tioning (Barth & Klingberg, 1988; Huston & Staubli, 1978; Kim & Routtenberg, 1976; LePiane & Phillips, 1978; Mit- cham & Thomas, 1972; Pelleymounter, Schleisinger, Weh- mer, Hall, & Stewart, 1988; Pezze & Feldon, 2004; Routtenberg & Holzman, 1973; Thompson, 1978). Most of the results showing the involvement of SN in learning and memory were obtained by means of irrevers- ible lesion techniques causing memory impairment (Dowd & Dunnett, 2005; Meloni & Davis, 2000; Mitcham & Thomas, 1972; Miyoshi et al., 2002). One limitation of the irreversible lesion technique is that it does not allow the assessment of the role played by the chosen site in the sev- eral distinct postulated stages of mnemonic processing (acquisition, consolidation, and retrieval). Instead, this type of analysis is made possible by the reversible func- tional inactivation technique (Bures & Buresova, 1990). Using this technique it has been shown that the SN is involved in the consolidation of aversive conditioning. In fact, the immediate post-training administration of picro- toxin (Cobos-Zapian et al., 1996; Kim & Routtenberg, 1976), bicuculline (Cobos-Zapian et al., 1996) or substance * Corresponding author. Fax: +39 55 4379506. E-mail address: corrado.bucherelli@mail.uniW.it (C. Bucherelli).