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Supplementary Material: Neuronal Responding to a Novel Cue

Figure 9. Average integrated unit neuronal activity in the nucleus accumbens, anterior and posterior cingulate cortex, and basolateral nucleus of the amygdala in controls (top panel) and rabbits with ventral subicular lesions (bottom panel) during extinction in the original context with a novel CS in place of the CS+ used during conditioning. The data, in the form of z-scores normalized with respect to a 300 300-ms pre-CS baseline, are shown in 40 consecutive 10 10-ms intervals after the onset of the novel CS (black bars) and CS- (white bars). In controls, the cingulate cortices and basolateral nucleus of the amygdala were significantly activated by the presence of the novel CS, manifested as an enhanced responding to the novel CS relative to the response to the CS-. This enhancement was not seen in the nucleus accumbens of controls, but interestingly, it was found in the nucleus accumbens of rabbits with lesions of the ventral subiculum. Responding to the novel CS was unaffected by lesions in the remaining brain areas. These findings were supported by significant individual comparisons following the analyses of integrated activity (see Table 1). Consistent with our data, other studies have reported that the cingulate cortices and amygdala play a role in the detection of novel stimuli in rabbits and other species, including rodents, primates and humans (Burns, Annett, Kelley, Everitt, & Robbins, 1996; Downar, Crawley, Mikulis, & Davis, 2001; Gabriel, Poremba, Kang, Shenker, & Maren, unpublished manuscript; Moses, Sutherland, & McDonald, 2002; Rutishauser, Mamelak, & Schumna, 2006; Sparenborg & Gabriel, 1990; Wilson & Rolls, 1993; Zhu, Brown, McCabe, & Aggleton, 1995). Previous work has also suggested that the interaction of amygdalar and ventral subicular inputs in the nucleus accumbens may control behavioral responses to novel cues (Burns et al., 1996). Based on evidence that hippocampal inputs to the nucleus accumbens can gate amygdalar inputs (Groenewegen, Wright, Beijer, & Voorn, 1999; Mulder, Hodenpijl, & Lopes da Silva, 1998), it is possible that the loss of ventral subicular inputs in rabbits with lesions may allow amygdalar inputs to elicit more ample responses of nucleus accumbens neurons to the novel CS.

References

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to amygdala, ventral subiculum, medial prefrontal cortex, and nucleus accumbens on the reaction to novelty: iImplication for limbic-striatal interactions. Behavioral Neuroscience,110, 60-–73.

Downar, J., Crawley, A. P., Mikulis, D. J., & Davis, K. D. (2001). The effect of task relevance on the cortical response to changes in visual and auditory stimuli: an An event-related fMRI study. NeuroimageNeuroImage, 14, 1256-–1267.

Gabriel, M., Poremba, A., Kang, E., Shenker, J., & Maren, S. Dealing with the unexpected: Multi-site hippocampal and cingulothalamic neuronal and field potential responses to novel stimuli during rabbits’ performance of discriminative avoidance behavior. Unpublished manuscript, University of Illinois.

Groenewegen, H. J., Wright, C. I., Beijer, A. V., & Voorn, P. (1999). Convergence and segregation of ventral striatal inputs and outputs. Trends in Neurosciences,22, 561-–567.

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and hippocampus in responding to novel objects and contexts. Brain Research Bulletin,58, 517-–527.

Mulder, A. B., Hodenpijl, M. G., & Lopes da Silva, F. H. (1998). Electrophysiology of the hippocampal and amygdaloid projections to the nucleus accumbens of the rat: convergenceConvergence, segregation, and interaction of inputs. Journal of Neuroscience, 18, 5095-–5102.

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Sparenborg, S., & Gabriel, M. (1990). Neuronal encoding of conditional stimulus duration in the cingulate cortex and the limbic thalamus of rabbits. Behavioral Neuroscience, 104, 919-33.

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Table 1.

Analysis of Variance for Neuronal Activity During Extinction Analysis of Variance for Neuronal Activity During Extinction

Area / Term / F / Dfdf / p
Nucleus Accumbensaccumbens / L x T x S / 3.16 / 3, /66 / 0.04
Anterior Cingulate cingulate Cortexcortex / L x T x S x I / 1.56 / 117/, 2223 / 0.054
Posterior Cingulate cingulate Cortexcortex
Basolateral Amygdalaamygdala / T x S x I
T x S x I / 1.74
2.01 / 117/, 2106
117/, 1872 / 0.04
0.005

AbbreviationsNote.: L = Llesion (control or lesion);, T= tTraining Sstage (reinforced trials, original context extinction, novel context extinction, or novel CS extinction),; S = Sstimulus (CS+/novel CS or CS-),; I = 10 -ms Ppost -CS Iintervals following CS Oonset (40 levels).

Figure 9.