Neurotoxic lesions of the anterior claustrum influence cued fear memory in rats

Abstract

Background: The claustrum (CLA), a subcortical area between the insular cortex and striatum, innervates almost all cortical regions of the mammalian brain. There is growing evidence that CLA participates in many brain functions, including memory, cognition, and stress response. It is proposed that dysfunction or malfunction of the CLA might be the pathology of some brain diseases, including stress-induced depression and anxiety. However, the role of the CLA in fear memory and anxiety disorders remains largely understudied.

Methods: We evaluated the influences of neurotoxic lesions of the CLA using auditory-cued fear memory and anxiety-like behaviors in rats.

Results: We found that lesions of anterior CLA (aCLA) but not posterior CLA (pCLA) before fear conditioning attenuated fear retrieval, facilitated extinction, and reduced freezing levels during the extinction retention test. Post-learning lesions of aCLA but not pCLA facilitated fear extinction and attenuated freezing behavior during the extinction retention test. Lesions of aCLA or pCLA did not affect anxiety-like behaviors evaluated by the open field test and elevated plus-maze test.

Conclusion: These data suggested that aCLA but not pCLA was involved in fear memory and extinction. Future studies are needed to further investigate the anatomical and functional connections of aCLA subareas that are involved in fear conditioning, which will deepen our understanding of CLA functions.

Keywords: anxiety; claustrum; extinction; fear memory; retrieval.

Figure 1

Neurotoxic lesion of the anterior but not posterior CLA causes anterograde amnesia. (A) Timeline for the experiment. (B–E) Pre-learning aCLA lesions did not affect freezing behavior during fear conditioning (B), and extinction (E), but reduced freezing level during fear retrieval (C) and extinction retention test (E). (F–I) Pre-learning pCLA lesions did not affect freezing behavior during fear conditioning (F), retrieval (G), extinction (H), and extinction retention test (I). aCLA, anterior claustrum; pCLA, posterior claustrum. Data are expressed as mean ± SEM; n = 10-13/group; *p < 0.05.

Figure 2

Post-learning neurotoxic lesion of the anterior but not posterior CLA facilitates fear extinction. (A) Timeline for the experiment. (B) Rats that were assigned to the aCLA-Sham and aCLA-Lesion groups showed similar levels of fear learning. (C–E) Post-learning aCLA lesions reduced freezing level in the last but not other retrieval trials (C), facilitated extinction (D), and decreased freezing levels in the extinction retention test (E). (F–I) Post-learning pCLA lesions did not affect freezing behavior during fear conditioning (F), retrieval (G), extinction (H), and extinction retention test (I). aCLA, anterior claustrum; pCLA, posterior claustrum. Data are expressed as mean ± SEM; n = 6-7/group; *p < 0.05.

Figure 3

Neurotoxic lesion of the anterior or posterior CLA did not affect locomotion or anxiety-like behaviors. (A) Timeline for the experiment. (B, C) aCLA and pCLA lesions did not affect behavioral performances in the open field test. (D, E) aCLA and pCLA lesions did not affect behavioral performances in the elevated-plus maze test. aCLA, anterior claustrum; pCLA, posterior claustrum. Data are expressed as mean ± SEM; n = 8/group; *p < 0.05.

Figure 4

Examples and schematic representations of CLA sections with lesions. (A) Example images of brain sections with CLA lesions. (B) Schematic representations of lesion areas in the CLA in the study.