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Transl Psychiatry. 2018 Mar 6;8(1):60. doi: 10.1038/s41398-018-0106-x.

Fear extinction requires infralimbic cortex projections to the basolateral amygdala.

Author information

1
Bowles Center for Alcohol Studies, Curriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
2
Bowles Center for Alcohol Studies, Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
3
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse, NIH, Bethesda, MD, USA.
4
Bowles Center for Alcohol Studies, Curriculum in Neurobiology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. thomas_kash@med.unc.edu.
5
Bowles Center for Alcohol Studies, Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. thomas_kash@med.unc.edu.

Abstract

Fear extinction involves the formation of a new memory trace that attenuates fear responses to a conditioned aversive memory, and extinction impairments are implicated in trauma- and stress-related disorders. Previous studies in rodents have found that the infralimbic prefrontal cortex (IL) and its glutamatergic projections to the basolateral amygdala (BLA) and basomedial amygdala (BMA) instruct the formation of fear extinction memories. However, it is unclear whether these pathways are exclusively involved in extinction, or whether other major targets of the IL, such as the nucleus accumbens (NAc) also play a role. To address this outstanding issue, the current study employed a combination of electrophysiological and chemogenetic approaches in mice to interrogate the role of IL-BLA and IL-NAc pathways in extinction. Specifically, we used patch-clamp electrophysiology coupled with retrograde tracing to examine changes in neuronal activity of the IL and prelimbic cortex (PL) projections to both the BLA and NAc following fear extinction. We found that extinction produced a significant increase in the intrinsic excitability of IL-BLA projection neurons, while extinction appeared to reverse fear-induced changes in IL-NAc projection neurons. To establish a causal counterpart to these observations, we then used a pathway-specific Designer Receptors Exclusively Activated by Designer Drugs (DREADD) strategy to selectively inhibit PFC-BLA projection neurons during extinction acquisition. Using this approach, we found that DREADD-mediated inhibition of PFC-BLA neurons during extinction acquisition impaired subsequent extinction retrieval. Taken together, our findings provide further evidence for a critical contribution of the IL-BLA neural circuit to fear extinction.

PMID:
29507292
PMCID:
PMC5838104
DOI:
10.1038/s41398-018-0106-x
[Indexed for MEDLINE]
Free PMC Article

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