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Infralimbic cortex is required for learning alternatives to prelimbic promoted associations through reciprocal connectivity.

ABSTRACT: Prefrontal cortical areas mediate flexible adaptive control of behavior, but the specific contributions of individual areas and the circuit mechanisms through which they interact to modulate learning have remained poorly understood. Using viral tracing and pharmacogenetic techniques, we show that prelimbic (PreL) and infralimbic cortex (IL) exhibit reciprocal PreL?IL layer 5/6 connectivity. In set-shifting tasks and in fear/extinction learning, activity in PreL is required during new learning to apply previously learned associations, whereas activity in IL is required to learn associations alternative to previous ones. IL?PreL connectivity is specifically required during IL-dependent learning, whereas reciprocal PreL?IL connectivity is required during a time window of 12-14?h after association learning, to set up the role of IL in subsequent learning. Our results define specific and opposing roles of PreL and IL to together flexibly support new learning, and provide circuit evidence that IL-mediated learning of alternative associations depends on direct reciprocal PreL?IL connectivity.

SUBMITTER: Mukherjee A

PROVIDER: S-EPMC6045592 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Infralimbic cortex is required for learning alternatives to prelimbic promoted associations through reciprocal connectivity.

Mukherjee Arghya A Caroni Pico P

Nature communications 20180713 1

Prefrontal cortical areas mediate flexible adaptive control of behavior, but the specific contributions of individual areas and the circuit mechanisms through which they interact to modulate learning have remained poorly understood. Using viral tracing and pharmacogenetic techniques, we show that prelimbic (PreL) and infralimbic cortex (IL) exhibit reciprocal PreL↔IL layer 5/6 connectivity. In set-shifting tasks and in fear/extinction learning, activity in PreL is required during new learning to ...[more]

PMID: 30006525

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Project description:The experience of traumatic stress can engender lasting memories associated with the trauma, often resulting in post-traumatic stress disorder (PTSD). However, only a minority of individuals develop PTSD symptoms upon exposure. The neurobiological mechanisms underlying the pathology of PTSD are poorly understood. Utilizing a rat model of PTSD, the Single Prolonged Stress (SPS) paradigm, we were able to differentiate between resilient and susceptible individuals. Fourteen days after the SPS exposure, we conducted the behavioral analyses using Elevated Plus Maze (EPM) and Open Field (OF) tests to identify male rats as trauma resilient or susceptible. We focused on the microRNA (miRNA) profiles of the infralimbic (IL) and prelimbic (PL) cortical regions, known to be crucial in regulating the stress response. Our investigation of stressed rats exposed to the SPS procedure yielded divergent response, and differential expression microRNAs (DEmiRs) analysis indicated significant differences in the IL and PL transcriptional response. In the IL cortex, the GO analysis revealed enriched GO terms in the resilient versus control comparison, specifically related to mitogen-activated protein kinase and MAP kinase signaling pathways for their molecular functions as well as cytosol and nucleoplasm for the biological process. In the susceptible versus resilient comparison, the changes in molecular functions were only manifested in the functions of regulation of transcription involved in the G1/S transition of the mitotic cell cycle and skeletal muscle satellite cell activation. However, no enriched GO terms were found in the susceptible versus control comparison. In the PL cortex, results indicated that the DEmiRs were enriched exclusively in the cellular component level of the endoplasmic reticulum lumen in the comparison between resilient and control rats. Overall, our study utilized an animal model of PTSD to investigate the potential correlation between stress-induced behavioral dysfunction and variations in miRNA expression. The aforementioned discoveries have the potential to pave the way for novel therapeutic approaches for PTSD, which could involve the targeted regulation of transcriptome expression.

Dataset Information

Infralimbic cortex is required for learning alternatives to prelimbic promoted associations through reciprocal connectivity.

Publications

Infralimbic cortex is required for learning alternatives to prelimbic promoted associations through reciprocal connectivity.

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