Plasticity Requirements in IL-to-BLA Circuitry During Extinction Learning


Allison Velie

Document Type


Publication Date

Summer 2023



JAX Location

In: Student Reports, Summer 2023, The Jackson Laboratory


Distinguishing threatening situations from neutral ones is incredibly important for survival. In humans, failure to change perception of conditioned cues from threatening to irrelevant (colloquially called 'extinction’) is thought to underlie PTSD and generalized anxiety disorders. By harnessing the mouse as a model organism to investigate the underlying neurobiology of extinction, we leveraged viral and transgenic tools to investigate neural plasticity during fear extinction in the pathway formed between the infralimbic cortex and the basolateral amygdala (IL- to-BLA circuit). Our hypothesis is that 1) cellular markers of plasticity are expressed in these neurons during extinction learning, and that 2) the plasticity-related gene Cdh2 is required in these neurons for extinction learning. In two experiments, mice were first conditioned to expect a brief foot shock after an auditory tone and anticipatory behavioral responses (i.e., immobility) were recorded. Mice were then placed in a new context where the tone was repeatedly presented without the foot shock to induce extinction learning. In the first experiment, viral strategies were combined with confocal microscopy to determine the fraction of IL-to-BLA neurons expressing the activity- dependent markers cFos or FosB. In the second, a combined viral and transgenic strategy was used to delete the plasticity-related Cdh2 gene specifically from IL-to-BLA neurons and extinction- related behaviors were recorded during the assay. Results from these experiments will lay the groundwork for understanding the plasticity requirements in the brain for extinction learning. Ultimately, such insights might reveal new therapeutic targets for PTSD and generalized anxiety disorder.

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