Perirhinal cortex supports acquired fear of auditory objects

Abstract

Damage to rat perirhinal cortex (PR) profoundly impairs fear conditioning to 22kHz ultrasonic vocalizations (USVs), but has no effect on fear conditioning to continuous tones. The most obvious difference between these two sounds is that continuous tones have no internal temporal structure, whereas USVs consist of strings of discrete calls separated by temporal discontinuities. PR was hypothesized to support the fusion or integration of discontinuous auditory segments into unitary representations or "auditory objects". This transform was suggested to be necessary for normal fear conditioning to occur. These ideas naturally assume that the effect of PR damage on auditory fear conditioning is not peculiar to 22kHz USVs. The present study directly tested these ideas by using a different set of continuous and discontinuous auditory cues. Control and PR-damaged rats were fear conditioned to a 53kHz USV, a 53kHz continuous tone, or a 53kHz discontinuous tone. The continuous and discontinuous tones matched the 53kHz USV in terms of duration, loudness, and principle frequency. The on/off pattern of the discontinuous tone matched the pattern of the individual calls of the 53kHz USV. The on/off pattern of the 50kHz USV was very different from the patterns in the 22kHz USVs that have been comparably examined. Rats with PR damage were profoundly impaired in fear conditioning to both discontinuous cues, but they were unimpaired in conditioning to the continuous cue. The implications of this temporal discontinuity effect are explored in terms of contemporary ideas about PR function.

Figure 1

Features of the three auditory cues that were used as conditional stimuli. (A) Spectrogram of the 53 kHz USV. (B) Spectrogram of the 53 kHz discontinuous tone. (C) Spectrogram of the 53 kHz continuous tone. (D) Amplitude plot of the 53 kHz USV.

Figure 2

Coronal sections from an animal in the sham-operated control group (PBS; Panels A through C) and an animal in the neurotoxic-lesioned group (NMDA; Panels D through G). Panels A and D are Nissl-stained sections; panels B and E are myelin-stained sections; and panels C and F are NeuN-stained sections. Panel G shows unilateral NeuN-stained sections taken at eight different anterior-posterior locations (from −3.3 to −6.8 mm relative to Bregma).

Figure 3

Amount of neurotoxic damage in six different brain regions. The open and filled bars represent the left and right hemispheres, respectively. The asterisk denotes a significant difference between left and right hemispheres in the mean amount of damage. Error bars represent ± 1 SE. Abbreviations: PR, perirhinal cortex; EC, entorhinal cortex; AM, amygdala; vHC, ventral hippocampus; TE, temporal cortex; and pIC; posterior insular cortex.

Figure 4

Effects of perirhinal lesions on conditional freezing in response to each of the three auditory cues. (A) Mean percent freezing to the 53 kHz tone, the 53 kHz discontinuous tone (tone pips), and the 53 kHz USV during cue testing in a shifted context. The open and filled bars represent, respectively, mean freezing levels in the sham-operated control group and the neurotoxic-lesioned group. Asterisks denote significant group differences. (B) Time course of freezing, in response to the continuous tone, in the sham-operated control group (open squares) and the lesioned group (filled squares). There were no significant group differences before or during the presentation of the cue. (C) Time course of freezing, in response to the discontinuous tone (pips), in the sham-operated control group (open squares) and the lesioned group (filled squares). There were significant group differences in all three time periods after the cue presentation, but no significant differences during the baseline period. (D) Time course of freezing, in response to the USV, in the sham-operated group (open squares) and the lesioned group (filled squares). There were significant differences in all three time periods after the cue presentation, but no significant differences during the baseline period. Error bars represent ± 1 SE.

Figure 5

Effects of PR lesions on conditional freezing to the training context. (A) Mean percent freezing to the training context in all three cue groups. Freezing was significantly depressed in the lesioned group (filled bars) relative to the sham-operated control group (open bars). Group differences in mean freezing levels are indicated by an asterisk. (B) Time course of freezing to the conditioning context among animals that were conditioned to the continuous tone. There were significant differences between the lesioned animals (filled squares) and control animals (open squares) in three of the four 2-min time periods. (C) Time course of freezing to the conditioning context among animals that were conditioned to the discontinuous tone. There were significant differences between the lesioned animals (filled squares) and control animals (open squares) in all four time periods. (D) Time course of freezing to the conditioning context among animals that were conditioning to the USV. There were significant differences between the lesioned animals (filled squares) and control animals (open squares) in all four time periods. Error bars represent ± 1 SE.