Auditory trace fear conditioning requires perirhinal cortex

Abstract

The hippocampus is well-known to be critical for trace fear conditioning, but nothing is known about the importance of perirhinal cortex (PR), which has reciprocal connections with hippocampus. PR damage severely impairs delay fear conditioning to ultrasonic vocalizations (USVs) and discontinuous tones (pips), but has no effect on delay conditioning to continuous tones (KholodarSmith, Allen, and Brown, in press). Here we demonstrate that trace auditory fear conditioning also critically depends on PR function. The trace interval between the CS offset and the US onset was 16 s. Pre-training neurotoxic lesions were produced through multiple injections of N-methyl-D-aspartate along the full length of PR, which was directly visualized during the injections. Control animals received injections with phosphate-buffered saline. Three-dimensional reconstructions of the lesion volumes demonstrated that the neurotoxic damage was well-localized to PR and included most of its anterior-posterior extent. Automated video analysis quantified freezing behavior, which served as the conditional response. PR-damaged rats were profoundly impaired in trace conditioning to either of three different CSs (a USV, tone pips, and a continuous tone) as well as conditioning to the training context. Within both the lesion and control groups, the type of cue had no effect on the mean CR. The overall PR lesion effect size was 2.7 for cue conditioning and 3.9 for context conditioning. We suggest that the role of PR in trace fear conditioning may be distinct from some of its more perceptual functions. The results further define the essential circuitry underlying trace fear conditioning to auditory cues. Keywords ultrasonic vocalizations; parahippocampal; discontiguous information; auditory objects; context conditioning Several lines of evidence suggest that perirhinal cortex (PR) functions to bind separate stimulus elements together into unitary representations Barense, Bussey, Lee, Rogers, Davies, Saksida, Murray, and Graham, 2005;Buffalo et al., 2006;Graham, Scahill, Hornberger, Barense, Lee, Bussey, and Saksida, 2006;Murray, Bussey, and Saksida, 2007; Kholodar-Smith, Allen, and Brown, in press). First, PR damage severely impairs performance on object-recognition tasks (Murray and Bussey, 1999; Bussey, Saksida, Address correspondence: Thomas H. Brown, Department of Psychology, Yale University, 2 Hillhouse Ave., New Haven, CT 06520,, Email: thomas.brown@yale.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. and Murray, 2002;Petrulis and Eichenbaum, 2003;Norman and Eacott, 2004;Lee et al., 2005;B...

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“…For instance, neural activity in the monkey PRC has been shown to reflect learning about objects that are cues for upcoming rewards 47 , and this learning is abolished following lesions to the PRC 48 or interference with dopamine D2 receptors in the PRC 49 . In rats, PRC lesions impair fear conditioning to complex auditory [50][51][52] or olfactory object cues 53 , and PRC neurons show increased firing during the presentation of auditory objects that have been associated with an aversive, unconditioned stimulus 54 .…”

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