A prefrontal-bed nucleus of the stria terminalis circuit limits fear to uncertain threat
In many cases of trauma, the same environmental stimuli that become associated with aversive events are experienced on other occasions without adverse consequence. We examined neural circuits underlying partially reinforced fear (PRF), whereby mice received tone-shock pairings on half of conditioning trials. Tone-elicited freezing was lower after PRF conditioning than fully reinforced fear (FRF) conditioning, despite an equivalent number of tone-shock pairings. PRF preferentially activated medial prefrontal cortex (mPFC) and bed nucleus of the stria terminalis (BNST). Chemogenetic inhibition of BNST-projecting mPFC neurons increased PRF, not FRF, freezing. Multiplexing chemogenetics with in vivo neuronal recordings showed elevated infralimbic cortex (IL) neuronal activity during CS-onset and freezing-cessation; these neural correlates were abolished by chemogenetic mPFC®BNST inhibition. These data suggest mPFC®BNST neurons limit fear to threats with a history of partial association with an aversive stimulus, with potential implications for understanding the neural basis of trauma-related disorders.
Some of the data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for Figure 1.
Article and author information
National Institute on Alcohol Abuse and Alcoholism (NIAAA-IRP)
- Andrew Holmes
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Animal experimentation: All experimental procedures were approved by the NIAAA (protocol # LBGN-AH-01) and Santa Clara University (SCU AWA: D18-01042) Animal Care and Use Committees and followed the NIH guidelines outlined in 'Using Animals in Intramural Research' and the local Animal Care and Use Committees.
- Mihaela D Iordanova, Concordia University, Canada
- Received: July 7, 2020
- Accepted: December 11, 2020
- Accepted Manuscript published: December 15, 2020 (version 1)
- Version of Record published: February 22, 2021 (version 2)
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
- Page views
Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
One signature of the human brain is its ability to derive knowledge from language inputs, in addition to nonlinguistic sensory channels such as vision and touch. How does human language experience modulate the mechanism by which semantic knowledge is stored in the human brain? We investigated this question using a unique human model with varying amounts and qualities of early language exposure: early deaf adults who were born to hearing parents and had reduced early exposure and delayed acquisition of any natural human language (speech or sign), with early deaf adults who acquired sign language from birth as the control group that matches on nonlinguistic sensory experiences. Neural responses in a semantic judgment task with 90 written words that were familiar to both groups were measured using fMRI. The deaf group with reduced early language exposure, compared with the deaf control group, showed reduced semantic sensitivity, in both multivariate pattern (semantic structure encoding) and univariate (abstractness effect) analyses, in the left dorsal anterior temporal lobe (dATL). These results provide positive, causal evidence that language experience drives the neural semantic representation in the dATL, highlighting the roles of language in forming human neural semantic structures beyond nonverbal sensory experiences.
Across phyla, males often produce species-specific vocalizations to attract females. Although understanding the neural mechanisms underlying behavior has been challenging in vertebrates, we previously identified two anatomically distinct central pattern generators (CPGs) that drive the fast and slow clicks of male Xenopus laevis, using an ex vivo preparation that produces fictive vocalizations. Here, we extended this approach to four additional species, X. amieti, X. cliivi, X. petersii, and X. tropicalis, by developing ex vivo brain preparation from which fictive vocalizations are elicited in response to a chemical or electrical stimulus. We found that even though the courtship calls are species-specific, the CPGs used to generate clicks are conserved across species. The fast CPGs, which critically rely on reciprocal connections between the parabrachial nucleus and the nucleus ambiguus, are conserved among fast-click species, and slow CPGs are shared among slow-click species. In addition, our results suggest that testosterone plays a role in organizing fast CPGs in fast-click species, but not in slow-click species. Moreover, fast CPGs are not inherited by all species but monopolized by fast-click species. The results suggest that species-specific calls of the genus Xenopus have evolved by utilizing conserved slow and/or fast CPGs inherited by each species.