Biology subjects

Tsutsui, K.-I.

Publications and source records attributed to Tsutsui, K.-I..

9 recordsLinked to original sources

bioRxiv2026

Neural mechanisms of self-conformity

We conform not only to the opinions and behaviors of others but also to those of ourselves, suggesting that the motivation to appear consistent leads us to treat ourselves like others. However, the neural mechanisms of self-conformity remain unclear. We used a sequential facial attractiveness-rating task with ostensible reminders of participants own previous ratings to investigate self-conformity and compare it against group conformity. Rating data showed that participants on average conformed to both themselves and the group. While some individuals conformed excessively (over-conformity), others went against their previous behavior (anti-conformity), similarly in self and group conditions. Neurally, dorsomedial and ventrolateral prefrontal cortex activity correlated with both self- and group conformity. Moreover, self-versus group conformity engaged more medial versus lateral prefrontal regions, and over-versus anti-conformity more ventral versus dorsal regions. These results suggest that self- and group conformity rely on both common and dedicated neural mechanisms.

neuroscience↗

bioRxiv2026

GABAergic projection from the subiculum to the medial entorhinal cortex in mice and rats

The subiculum (SUB) is a major hippocampal output hub that routes information to cortical and subcortical targets, and its long-range projections are considered excitatory. Using enhancer-driven adeno-associated viral vectors to selectively label {gamma}-aminobutyric acid (GABA)-releasing neurons across species, here we show that the dorsal SUB also sends an inhibitory projection to the dorsal part of the medial entorhinal cortex (MEC) in mice and rats. Anterograde tracing in mice revealed that the dorsal SUB contains GABAergic neurons that project sparsely to all layers of the dorsal MEC with enrichment in superficial layers, in contrast to the glutamatergic SUB axons targeting MEC layer V. Slice electrophysiology demonstrated that these GABAergic axons form inhibitory synapses in the MEC. A subset of projecting neurons expressed parvalbumin (PV), whereas somatostatin-positive neurons were rare. Consistently, PV neuron-specific anterograde tracing recapitulated the SUB-to-MEC projection. In rats, subicular GABAergic axons were enriched in MEC layer II, and SynaptoTAG2-labeled presynaptic boutons were positive for the vesicular GABA transporter, supporting inhibitory synapse formation. Anterograde tracing of PV neurons similarly recapitulated the laminar axonal distribution in the MEC. These results identify a conserved PV-associated inhibitory SUB-to-MEC projection with species-specific laminar organization, extending the canonical excitatory view of subicular output.

neuroscience↗

bioRxiv2026

Mapping mouse hippocampal output circuits using direction-selective anterograde transsynaptic transduction

The hippocampus and its projection targets constitute hippocampal output circuits that are essential for memory, navigation, and emotional regulation. Although cortical and subcortical regions receiving hippocampal projections have been well characterized, it remains unclear how hippocampal signals are processed within these projection target regions. To precisely understand information processing in hippocampal output circuits, it is therefore important to gain genetic access to neuronal subpopulations receiving direct hippocampal inputs for structural and functional analyses. Anterograde transsynaptic transduction using adeno-associated virus (AAV) serotype 1 has emerged as a powerful approach for targeting postsynaptic neurons, but its application is limited by unintended retrograde transport, which leads to false-positive labeling in reciprocally connected circuits. Here, we developed a direction-selective anterograde transsynaptic transduction by combining AAV vectors with distinct infection properties and an intersectional gene expression system. Using the hippocampal-entorhinal circuit, we identified an optimal viral combination that enables predominantly anterograde transsynaptic labeling. We further applied this method to map hippocampal projections to reciprocally connected regions, including the amygdala, providing a robust approach for dissecting complex hippocampal output circuits.

neuroscience↗

bioRxiv2026

Anterior cingulate cortex projections to the amygdala in primates: topographic and layer-specific organization underlying emotion and mood regulation

Emotion and mood regulation critically depends on interactions between the anterior cingulate cortex (ACC) and the amygdala. However, the detailed architecture of ACC projections to their major targets, the basal (BA) and accessory (AcBA) basal nuclei of the amygdala, remains unclear. To address this issue, a combined retrograde and anterograde tracing with viral vectors were performed in macaques to map the projection patterns from pregenual (pgACC), subgenual (sgACC), and dorsal (dACC) subareas. Data revealed that ACC neurons projecting to the BA arose predominantly from the superficial layers (II/III) of all subareas and the deep layers (V/VI) of the sgACC, whereas ACC neurons projecting to the AcBA originated mainly in the deep layers of the sgACC and dACC. The present study defines the topographic and layer-specific organization of ACC-amygdala connectivity in primates and subserves to provide an anatomical basis for future causal and translational approaches, such as targeted interventions against ACC-related mood disorders. TeaserPrimate anterior cingulate cortex has topographic and layer-specific projections to amygdala that are involved in emotion and mood regulation.

neuroscience↗

bioRxiv2024

Dorsal-caudal and ventral hippocampus target different cell populations in the medial frontal cortex in rodents

Direct projections from the ventral hippocampus (vHPC) to the medial frontal cortex (MFC) play crucial roles in memory and emotional regulation. Using anterograde transsynaptic tracing and in vitro electrophysiology in mice, we document a previously unexplored pathway that parallels the established vHPC-MFC connectivity. This pathway connects the dorsal-caudal hippocampus (dcHPC) to specific subregions of the ventral MFC, in particular the dorsal peduncular cortex. Notably, this pathway exerts a strong inhibitory influence on ventral MFC by targeting a substantial proportion of inhibitory neurons. Retrograde transsynaptic tracing in rats indicated that ventral MFC subregions project disynaptically back to vHPC. These results, altogether, suggest the existence of a remarkable functional circuit connecting distinct functional areas: the cognition-related dcHPC with the emotion-related ventral MFC and vHPC. These findings further provide valuable insights in the cognitive and emotional abnormalities associated with the HPC-MFC connectivity in neurological and psychiatric disorders.

neuroscience↗

bioRxiv2022

Mechanisms of adjustments to different types of uncertainty in the reward environment across mice and monkeys

Despite being unpredictable and uncertain, reward environments often exhibit certain regularities, and animals navigating these environments try to detect and utilize such regularities to adapt their behavior. However, successful learning requires that animals also adjust to uncertainty associated with those regularities. Here, we analyzed choice data from two comparable dynamic foraging tasks in mice and monkeys to investigate mechanisms underlying adjustments to different types of uncertainty. In these tasks, animals selected between two choice options that delivered reward probabilistically, while baseline reward probabilities changed after a variable number (block) of trials without any cues to the animals. To measure adjustments in behavior, we applied multiple metrics based on information theory that quantify consistency in behavior, and fit choice data using reinforcement learning models. We found that in both species, learning and choice were affected by uncertainty about reward outcomes (in terms of determining the better option) and by expectation about when the environment may change. However, these effects were mediated through different mechanisms. First, more uncertainty about the better option resulted in slower learning and forgetting in mice, whereas it had no significant effect in monkeys. Second, expectation of block switches accompanied slower learning, faster forgetting, and increased stochasticity in choice in mice, whereas it only reduced learning rates in monkeys. Overall, while demonstrating the usefulness of entropy-based metrics in studying adaptive behavior, our study provides evidence for multiple types of adjustments in learning and choice behavior according to uncertainty in the reward environment.

neuroscience↗

bioRxiv2022

Hippocampal-medial entorhinal circuit is differently organized along the dorsoventral axis in rodents

The general understanding of hippocampal circuits is that the hippocampus and the entorhinal cortex (EC) are topographically connected through parallel identical circuits along the dorsoventral axis. Our anterograde tracing and in vitro electrophysiology data, however, show a markedly different dorsoventral organization of the hippocampal projection to the medial EC (MEC). Whereas dorsal hippocampal projections are confined to the dorsal MEC and preferentially target layer Vb (LVb) over layer Va (LVa) neurons, the ventral hippocampus innervates the entire dorsoventral extent of MEC. In the ventral MEC, these projections innervate neurons in both LVa and LVb. In contrast, in the dorsal MEC, ventral hippocampal projections target mainly LVa neurons. As LVa neurons project to telencephalic structures, our findings indicate that the ventral hippocampus regulates LVa-mediated entorhinal-neocortical output from both the dorsal and ventral MEC. Overall, the marked dorsoventral differences in hippocampal-entorhinal connectivity impose important constraints on signal flow in hippocampal-neocortical circuits.

neuroscience↗

bioRxiv2022

Hippocampal CA1 represents action and reward events instantly compared to the superficial and deep layers of the lateral entorhinal cortex

The entorhinal cortex (EC) is the main interface between the hippocampus and the neocortex. The EC plays a critical role in learning and memory. We investigated the neuronal representation of behavioral events during operant learning in the hippocampal-entorhinal circuit of head-fixed rats. Both CA1 and lateral entorhinal cortex (LEC) neurons develop task-related activities after learning. Among diverse task-related activities, we compared the transient peak activities that represent action and reward and found a distinct difference in the timing of behavioral event representation between CA1 and LEC. CA1 represents action and reward events in close to real-time, whereas both the superficial and deep layers of the LEC showed delayed representation of those events. Our results suggest that subpopulations exist within which CA1 and LEC neurons process the information in a different order from the anatomically defined hippocampal-entorhinal circuit.

neuroscience↗

bioRxiv2021

Depression-like state induced by low-frequency repetitive transcranial magnetic stimulation to ventral medial frontal cortex in monkeys

The medial frontal cortex (MFC), especially its ventral part, has long been of great interest with respect to the pathology of mood disorders. A number of human brain imaging studies have demonstrated the abnormalities of this brain region in patients with mood disorders, however, whether it is critically involved in the pathogenesis of such disorders remains to be fully elucidated. In this study, we conducted a causal study to investigate how the suppression of neural activity in the ventral region of the MFC (vMFC) affects the behavioral and physiological states of monkeys by using repetitive transcranial magnetic stimulation (rTMS). By using low-frequency rTMS (LF-rTMS) as an inhibitory intervention, we found that LF-rTMS targeting the vMFC induced a depression-like state in monkeys, which was characterized by a reduced spontaneous behavioral activity, increased plasma cortisol level, impaired sociability, and decreased motivation level. On the other hand, no such significant changes in behavioral and physiological states were observed when targeting the other MFC regions, dorsal or posterior. We further found that the administration of an antidepressant agent, ketamine, ameliorated the abnormal behavioral and physiological states induced by the LF-rTMS intervention. These findings indicate the causal involvement of the vMFC in the regulation of mood and affect and the validity of the LF-rTMS-induced dysfunction of the vMFC as a nonhuman primate model of the depression-like state.

neuroscience↗