Austin
Choi

Mimicking and rescuing isolation-induced inflexibility via chemogenetic modulation of the vHC

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Authors:

Austin Choi

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Background: Flexible behavior is defined as the ability for organisms to deviate from established behaviors by durably encoding new information and using newly formed memories to guide future choices. Chemogenetic tools, such as DREADDs, can be used to modulate the neural circuits involved with the formation of flexible behaviors. Here, we tested whether ventral hippocampus (vHC) projections to the ventrolateral orbitofrontal cortex (VLO) contribute to adolescent isolation-induced deficits in flexible behavior. Methods: C57BL/6 mice were randomly assigned to single or group housing during adolescence. In adulthood, single-housed mice were reintegrated into groups such that cages contained both previously isolated and group-housed mice. Chemogenetic strategies were used to investigate the role of excitatory neurons in the vHC in flexible behavior. To quantify behavioral flexibility mice were trained to generate two distinct responses for food, then one response ceased to be reinforced. Immunohistochemistry was used to quantify cFos levels in the vHC. Results: Social isolation impairs flexible behavior and is associated with increased cFos levels in the vHC. Chemogenetically stimulating vHC-VLO projections mimics isolation-induced inflexible behavior, which is rescued by chemogenetic inhibition of these neurons. cFos levels are increased in mice expressing Gq-DREADDs. Conclusion: Chemogenetic stimulation changed neuronal activity, as measured through cFos, as expected. 16

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Columbia / Biology / 2027

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Austin Choi