[F31] Integrated Mechanisms for Corticostriatal Control of Action
Ente: National Institute of Mental Health
Scadenza: 2029-07-05
Importo max: 50.114 EUR
Paese: US
Descrizione
SUMMARY
One key challenge we face in day-to-day life is the explore/exploit dilemma: deciding whether to try new
methods (exploration) or stick with proven strategies (exploitation). For instance, when conducting an
experiment, one might choose between a familiar technique that has worked in the past or a new, less familiar
approach. Understanding how our brains make these decisions is key to understanding how organisms can
survive in complex and evolving environments. The orbitofrontal cortex (OFC), premotor cortex (M2), and
dorsomedial striatum (DMS) appear to individually influence the balance between exploration and exploitation;
however, it is unclear whether or how these brain regions interact to coordinate this behavior. The goal of this
proposal is to define how the OFC-M2-DMS circuit supports action exploration or exploitation.
Recently, my lab identified specific “memory trace” neurons in the OFC that represent the best strategy
to obtain a reward, allowing mice to exploit optimal actions in a changing reward context. Specifically, mice were
trained to obtain foods using multiple response strategies, then reward likelihood decreased for one strategy and
was maintained for another. Memory trace neurons are active when reward contingencies change, and again
when mice must recall the best strategy to use when they seek food reward in the future (i.e., memory retrieval).
Inactivating these trace neurons during memory retrieval impairs the ability of mice to recall the best strategy to
obtain a reward, impairing exploitative behavior. Whether and how memory trace neurons interact with other
brain regions to implement optimal reward-seeking strategies remains unclear.
Previous studies have shown that chemogenetic inactivation of OFC-to-M2 projections blocks the
capacity of mice to seek valued outcomes, and M2-to-DMS connections are thought to convey action-related
aspects of prior experiences to drive behavior. Despite these findings, specific cell types, learning processes,
and motor outputs have not been defined, in part because M2 is largely neglected in decision-making research.
Aim 1 will determine how the OFC, including memory trace neurons in the OFC, interacts with M2 to
allow mice to use optimal action strategies for exploitative behavior. I will use multi-site chemogenetic and Fos-
Targeted Recombination in Active Populations (TRAP) techniques to address this question. Aim 2 will determine
the outputs by which M2 coordinates the exploitation of optimal action strategies through projections to DMS.
First, I will use chemogenetics to test whether M2-to-DMS connections are necessary for mice to exploit optimal
action strategies. Then, I will use fiber photometry to record neural activity in the M2 and DMS in mice during
exploitative behavior. Collectively, these aims will expand our understanding of the contribution of the circuitry
between OFC, M2, and DMS to exploitative behavior.
Completing these aims will enhance my current co
Istituzione: EMORY UNIVERSITY
PI: Lisette Bahena
Progetto: 1F31MH143554-01
Settori: National Institute of Mental Health
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