UNCONDITIONED STIMULUS PATHWAYS TO THE AMYGDALA: EFFECTS OF POSTERIOR THALAMIC AND CORTICAL LESIONS ON FEAR CONDITIONING E. LANUZA, a,b * K. NADER a,c AND J. E. LEDOUX a a Center for Neural Science, New York University, New York, NY 10003, USA b Dept de Biologia Cellular, Fac. CC. Biolo ` giques, Universitat de Va- le ` ncia, Burjassot, Vale ` ncia 46100, Spain c Department of Psychology, McGill University, Montreal, Quebec, Canada H3A 1B1 Abstract—Plasticity in the lateral nucleus of the amygdala is thought to be critical for the acquisition of Pavlovian fear conditioning. The pathways that transmit auditory condi- tioned stimulus information originate in auditory processing regions of the thalamus and cortex, but the pathways medi- ating transmission of unconditioned stimuli to the amygdala are poorly understood. Recent studies suggest that somato- sensory (footshock) unconditioned stimulus information is also relayed in parallel to the lateral nucleus of the amygdala from the thalamus (the posterior intralaminar thalamic com- plex, PIT) and the cortex (parietal insular cortex). In the present study we reexamined this issue. Our results showed that bilateral electrolytic lesions of the PIT alone blocked fear conditioning, whereas bilateral excitotoxic PIT lesions had no effect. These electrolytic PIT lesions did not affect fear con- ditioning using a loud noise as unconditioned stimulus, de- fining the effects of PIT lesions as a disruption of somato- sensory as opposed to auditory processing. Finally, we per- formed combined bilateral excitotoxic lesions of the PIT nuclei and electrolytic lesions of the parietal insular cortex. These, like excitotoxic lesions of PIT alone, had no effect on the acquisition of fear conditioning. Thus, somatosensory regions of the thalamus and cortex may well be important routes of unconditioned stimulus transmission to the amyg- dala in fear conditioning, but information about the uncondi- tioned somatosensory stimulus is also transmitted from other sources that send fibers through, but do not form essential synapses in, the thalamus en route to the amygdala. © 2004 IBRO. Published by Elsevier Ltd. All rights reserved. Key words: emotional learning, pain, neurotoxic lesions, pos- terior intralaminar thalamic complex, footshock pathways. An extensive body of research indicates that in Pavlovian fear conditioning the formation of the association between an auditory conditioned stimulus (CS) and a footshock unconditioned stimulus (US) depends on the integrity of the lateral nucleus of the amygdala (LA; LeDoux et al., 1990a; Amorapanth et al., 2000; LeDoux, 2000; Maren, 2001a; Nader et al., 2001). Thus, CS and US inputs con- verge onto common cells in the LA (Romanski et al., 1993b; Bordi and LeDoux, 1994), the physiological re- sponses of cells in this region are modified during condi- tioning (Quirk et al., 1995; McKernan and Shinnick- Gallagher, 1997; Rogan et al., 1997; Maren, 1999a; Collins and Pare, 2000; Repa et al., 2001), and the activity of these cells during conditioning is necessary for the CS–US association, and thus learning, to occur (Helmstetter and Bellgowan, 1994; Muller et al., 1997; Wilensky et al., 2000a). The anatomical pathways through which auditory CS information reaches the amygdala are well character- ized and involve parallel transmission from the auditory thalamus and cortex to the LA (LeDoux et al., 1990b; Turner and Herkenham, 1991; Romanski and LeDoux, 1993; McDonald, 1998; Doron and LeDoux, 1999, 2000). These pathways have been shown to each be capable of mediating the relay of auditory information to the LA in fear conditioning tasks (Romanski and Le- Doux, 1992). Recently, Shi and Davis (1999) have suggested that US information might reach the LA from thalamic and cortical areas as well. This conclusion was based on the observation that lesions of the parietal insular cortex (PaIC), a region of somatosensory cortex that projects to the LA, had no effect on fear conditioning, but combined lesions of PaIC and the posterior thalamus, which receives somatosensory information and projects to the LA (LeDoux et al., 1987, 1990b), disrupted conditioning. However, this effect was not replicated in a later study (Brunzell and Kim, 2001). Shi and Davis (1999) did not lesion the posterior thal- amus alone since Romanski and LeDoux (1992) found that lesions in this region failed to disrupt fear conditioning. However, the thalamic lesions made by Romanski and LeDoux (1992) targeted the auditory processing regions of the posterior thalamus that project to the amygdala, namely the posterior intralaminar nucleus (PIN), medial division of the medial geniculate body (MGm), and the suprageniculate nucleus (SG). In contrast, the thalamic lesions that Shi and Davis (1999) used in combination with PaIC lesions included the PIN/MGm/SG complex as well *Correspondence to: E. Lanuza, Dept. de Biologia Cellular, Fac. CC. Biolo ` giques, Universitat de Vale `ncia, Campus de Burjassot, C. Dr. Moliner, 50 Burjassot, Vale ` ncia 46100, Spain. Tel: +34-96-354-3784; fax: +34-96-354-4372. E-mail address: enrique.lanuza@uv.es (E. Lanuza). Abbreviations: CS, conditioned stimulus; LA, lateral nucleus of the amygdala; MGm, medial geniculate nucleus, medial division; PaIC, parietal insular cortex; PIN, posterior intralaminar thalamic nucleus; PIT, posterior intralaminar thalamic complex; PoT, posterior triangular thalamic nucleus; SG, suprageniculate thalamic nucleus; SPFpv, par- vocellular subparafascicular thalamic nucleus; US, unconditioned stimulus. Neuroscience 125 (2004) 305–315 0306-4522/04$30.00+0.00 © 2004 IBRO. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.neuroscience.2003.12.034 305