Friday, April 19, 2024
4/19/2024
PROJECT SUMMARY Our decisions are influenced by recent experiences (i.e., history dependence). The control of history dependence relies on the posterior parietal cortex (PPC). However, PPC also serves many other functions such as working memory and sensorimotor control. This proposal aims to elucidate how PPC circuits perform multiple functions, a critical step towards identifying the causes and treatments of specific PPC malfunctions. We hypothesize that different functions involve different subcircuits in PPC, each with distinct input-output connectivity. We will test this hypothesis, focusing on the function of history dependence and two projection targets of PPC, the dorsal striatum (STR) and posterior secondary motor cortex (pM2). Although both targets have been implicated for history-dependent decisions, our preliminary results indicate that the PPC neurons projecting to each target are largely distinct, suggesting that the two pathways may have distinct functions. Here we propose to take three parallel approaches to uncover which of the two pathways mediates history dependence and to characterize long-range inputs to each pathway. First, we will compare the history bias information encoded by PPC neurons projecting to STR or pM2, using a combination of two-photon calcium imaging and retrograde labeling in mice exhibiting history-dependent decision bias. Second, we will determine the necessity of PPC-STR and PPC-pM2 pathways for history-dependent decisions, by optogenetically inactivating each pathway and assessing its effect on history-dependent bias. Lastly, we will map long-range inputs specific to the two pathways that contribute to the formation of history-dependent bias in PPC, using retrograde trans-synaptic rabies tracing. Together, the results will reveal whether PPC contains a subcircuit dedicated to history dependence and what constitutes the input and output pathways of that subcircuit. Answers to these questions will lay the solid groundwork for future research that delineates the inter-areal circuits underlying decision-making and other PPC functions. Furthermore, the identification of function-specific pathways may point to neural substrates for targeted intervention with less risk of compromising other functions.
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