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Amemori, K.-i.

Publications and source records attributed to Amemori, K.-i..

5 recordsLinked to original sources

The mental conflict in risk-taking behavior: Decoding bias between optimism and pessimism

Humans and animals often face risky situations that require decision-making. Such decisions can be high-risk, high-return at some times, and low-risk, low-return at other times, depending on the balance between optimism and pessimism. However, how this optimism-pessimism bias is regulated across contexts remains unclear. Here, we introduced a computational model of decision-making in a risk-taking task based on the free-energy principle, together with a machine-learning framework that inversely estimates cognitive updating and optimism-pessimism bias from behavioral data. Applying this framework to monkey behavioral data, we found that a monkey quickly and accurately recognized the degree of risk, while frequently switching between optimism and pessimism during the task. In addition, we identified a characteristic control rule for optimism-pessimism bias that is distinct from reward-dependent regulation. Our framework provided a principled tool for understanding the latent cognitive processes underlying risky decision-making in animals and humans.

neuroscience↗

Bridge protein-mediated viral targeting of cells expressing endogenous μ-opioid G protein-coupled receptors in the mouse and monkey brain

Targeting specific cell types is essential for understanding their functional roles in the brain. Although genetic approaches enable cell-type-specific targeting in animals, their application to higher mammalian species, such as nonhuman primates, remains challenging. Here, we developed a nontransgenic method using bridge proteins to direct viral vectors to cells endogenously expressing -opioid receptors (MORs), a G protein-coupled receptor. The bridge protein comprises the avian viral receptor TVB, the MOR ligand {beta}-endorphin ({beta}ed), and an interdomain linker. EnvB-enveloped viruses bind to the TVB component, followed by the interaction of {beta}ed with MORs, triggering viral infection in MOR-expressing cells. We optimized the secretion signals, domain configurations, and interdomain linkers of the bridge proteins to maximize viral targeting efficiency and specificity. Alternative configurations incorporating different ligands and viral receptors also induced viral infection in MOR-expressing cells. The optimized {beta}ed-f2-TVB bridge protein with EnvB-pseudotyped lentiviruses induced infection in MOR-expressing cells in the striatum of mice and monkeys. An intersectional approach combining {beta}ed-f2-TVB with a neuron-specific promoter refined cell-type specificity. This study establishes the foundation for the rational bridge protein design and the feasibility of targeting G protein-coupled receptors beyond tyrosine kinase receptors, thereby expanding targetable cell types in the brain and throughout the body. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/637063v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1fe91org.highwire.dtl.DTLVardef@effe51org.highwire.dtl.DTLVardef@217d73org.highwire.dtl.DTLVardef@b31251_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

Functional Dichotomy of Orbitofrontal Cortex and Anterior Cingulate Cortex Subregions in Decision-Making and Brain-Body Regulation

Mood disorders are associated with complex disruptions in brain networks, including those associated with the orbitofrontal cortex (OFC) and pregenual anterior cingulate cortex (pACC). The functional contribution of the caudal OFC (cOFC) has remained largely unexplored. We investigated the functions of the cOFC and pACC in macaques performing an approach-avoidance task by the combination of multimodal recordings and electrical microstimulation (EMS) of the cOFC. We assessed neural, autonomic and behavioral responses. We found the cOFC to be sensitive to both positive and negative stimuli, whereas the pACC was singificantly more active during aversive outcomes. EMS of the cOFC increased avoidance behavior, suggesting a causal role for the OFC subdivision in cost-benefit decision-making. Physiological measurements were positively correlated with behavioral patterns, emphasizing body-brain synchronization during emotionally significant decision-making. We suggest that the cOFC contributes to inducing pessimistic states, thereby making its dysfunction a potential contributor to the etiology of mood disorders.

neuroscience↗

Multiplexed action-outcome representation by striatal striosome-matrix compartments detected with a novel cost-benefit foraging task

Learning about positive and negative outcomes of actions is crucial for survival and underpinned by conserved circuits including the striatum. How associations between actions and outcomes are formed is not fully understood, particularly when the outcomes have mixed positive and negative features. We developed a novel foraging ( bandit) task requiring mice to maximize rewards while minimizing punishments. By 2-photon Ca++ imaging, we monitored activity of 5831 identified anterodorsal striatal striosomal and matrix neurons. Surprisingly, we found that action-outcome associations for reward and punishment were combinatorially encoded rather than being integrated as overall outcome value. Single neurons could, for one action, encode outcomes of opposing valence. Striosome compartments consistently exhibited stronger representations of reinforcement outcomes than matrix, especially for high reward or punishment prediction errors. These findings demonstrate a remarkable multiplexing of action-outcome contingencies by single identified striatal neurons and suggest that striosomal neurons are differentially important in action-outcome learning.

neuroscience↗

Microstimulation of primate neocortex targeting striosomes induces negative decision-making

Affective judgment and decision-making are strongly modulated by the pregenual anterior cingulate (pACC) and caudal orbitofrontal (cOFC) cortical regions. By combining MRI-guided electrical microstimulation with viral tracing methods in non-human primates, we demonstrate that circumscribed pACC and cOFC microstimulation sites that induce negative decision-making preferentially project to striosomes in the anterior striatum. These results outline a behaviorally important circuit from pACC/cOFC to striosomes causally modulating decision-making under emotional conflict.

neuroscience↗