Biology subjects

Ogasawara, T.

Publications and source records attributed to Ogasawara, T..

5 recordsLinked to original sources

bioRxiv2026

A prefrontal cortex-hypothalamus circuit for heart rate control in non-human primates

Humans exhibit changes in heart rate during cognitive and emotional events, and dysregulation of this brain-heart coupling is a hallmark of many psychiatric disorders. Yet, how circuits that regulate cognition exert direct control over heart physiology remains poorly understood, particularly in primates. Here, we identify a prefrontal-hypothalamic circuit that exerts powerful, bidirectional control over heart rate in monkeys. We show that electrical stimulation of a small ventral subregion within the ventrolateral prefrontal cortex (area 47/12; a12) evokes rapid and robust decreases in heart rate and increases heart rate variability, whereas neighboring prefrontal regions produce weaker or no effects. And a12 neurons are coupled to heart rate on a moment-by-moment basis. Anatomical tracing data reveal projections from a12 to a circumscribed region of lateral hypothalamus (LHA), and stimulation of this LHA target recapitulates the cardiac effects of prefrontal activation. Consistent with a prefrontal-to-hypothalamus system for heart rate control, stimulation of LHA produces faster, stronger, state-independent heart effects, whereas stimulation of a12 produces effects that are sensitive to internal states. Oppositely to its activation, chemogenetic inactivation of a12 or its projections to LHA increases heart rate, demonstrating that this pathway can provide tonic inhibitory control over cardiac function. To make steps towards a more cell-type-specific and minimally invasive causal control of this circuit, we developed a primate sonogenetic approach based on ultrasound activation of CaMKII+ neurons virally transduced with TRPV1. Sonogenetic stimulation of a12 produced increases in heart rate variability, and these effects were attenuated by inactivation of LHA. Finally, we found that sonogenetic and chemogenetic perturbation of the same prefrontal region during a value-based decision-making task bidirectionally alters risky decision making. Together, our work identifies how a12 regulates heart rate and cognition, revealing a mechanistic substrate for brain-body interactions and a potential therapeutic target for disorders of cognitive-autonomic dysregulation.

neuroscience↗

bioRxiv2025

Temporal-orbitofrontal pathway regulates choices across physical reward and visual novelty

Perceptually novel objects have profound impacts on our daily decisions. People often pay to try novel meals over familiar ones, or to see novel visual scenes at art exhibits and travel destinations. This suggests that perceptual novelty and the value of physical rewards, such as food, interact at the level of neural circuits to guide decisions, but where and how is unknown. We designed a behavioral task to study this novelty-reward interaction in animals and to uncover its neural underpinnings. Subjects chose among familiar offers associated with different expectations of novel objects and different expectations of juice rewards. Expectation of novel objects increased the preference for expected rewards. This novelty-reward interaction was reflected by neural activity in the anterior ventral temporal cortex (AVMTC) - a region previously implicated in the detection and prediction of novelty - and in the orbitofrontal cortex (OFC) - an area that receives prominent AVMTC inputs and is known for its capacity to signal subjective value of visual objects. Neural activity patterns suggested that AVMTC was upstream of OFC in the decision process. Chemogenetic disruption of the AVMTC[->]OFC circuit altered the impact of expected novelty on the valuation of physical reward. Hence, the ventral visual system impacts novelty-reward interactions during decisions through direct projections to OFC.

neuroscience↗

bioRxiv2025

Successive failure triggered by motor exploration in a reinforcement-based reaching task

Motor exploration, a key process in reinforcement-based motor learning, is triggered by suboptimal performance and leads to increased movement variability. Consequently, failure in one trial may increase the likelihood of failure in subsequent trials. If this pattern emerges, successive failures (SFs) are not merely events to be avoided but part of the trial-and-error process of identifying optimal movements, which can facilitate motor learning. This study investigated whether and how SFs occur above chance levels during a motor learning task with binary success/failure feedback and explored the relationship between SFs and motor learning outcomes. Thirty-three healthy young adults participated in the study, performing a reaching task to pass through a target without visual feedback of their hand position. Binary feedback was provided after each trial, indicating whether the hand trajectory overlapped with the target. The results showed that the probability of two SFs was significantly higher than the square of the overall failure probability, indicating that failure streaks occurred above chance levels. A computational model, in which motor variability comprised constant motor noise and exploratory variability regulated by recent reward history (where variability increased following failure), successfully explained SF emergence. However, the learning index, defined as the difference in failure probability between the first and latter halves of the experiment, was unrelated to SF emergence. Additionally, failure streaks disappeared when participants were asked to reach one of seven randomly selected targets in each trial, suggesting that introducing environmental variability can help alleviate SFs.

neuroscience↗

bioRxiv2022

A neural mechanism for conserved value computations integrating information and rewards

Behavioral and economic theory dictates that we decide between options based on their values. However, humans and animals eagerly seek information about uncertain future rewards, even when this information does not provide any objective value. This implies that decisions can be made by endowing information with subjective value and integrating it with the value of extrinsic rewards, but the mechanism is unknown. Using a novel multi-attribute decision making task we found that human and monkey value judgements are regulated by strikingly conserved computational principles, including how they compute the value of information and scale it with informations timing and ability to resolve a specific form of uncertainty. We then identified a neural substrate in a highly conserved and ancient structure, the lateral habenula (LHb). LHb neurons signal the subjective value of choice options integrating the value of information with extrinsic rewards, and LHb activity both predicts and causally influences online decisions. Key input regions to LHb provide the necessary ingredients for these computations, but do not themselves signal an integrated value signal to guide multi attribute decisions. Our data thus identifies neural mechanisms of the conserved computations underlying multi-attribute, value-based decisions to seek information about the future.

neuroscience↗

bioRxiv2021

Neuronal mechanisms of novelty seeking

Humans and other primates interact with the world by observing and exploring visual objects. In particular, they often seek out the opportunities to view novel objects that they have never seen before, even when they have no extrinsic primary reward value. However, despite the importance of novel visual objects in our daily life, we currently lack an understanding of how primate brain circuits control the motivation to seek out novelty. We found that novelty-seeking is regulated by a small understudied subcortical region, the zona incerta (ZI). In a task in which monkeys made eye movements to familiar objects to obtain the opportunity to view novel objects, many ZI neurons were preferentially activated by predictions of future novel objects and displayed burst excitations before gaze shifts to gain access to novel objects. Low intensity electrical stimulation of ZI facilitated gaze shifts, while inactivations of ZI reduced novelty-seeking. Surprisingly, additional experiments showed that this ZI-dependent novelty seeking behavior is not regulated by canonical neural circuitry for reward seeking. The habenula-dopamine pathway, known to reflect reward predictions that control reward seeking, was relatively inactive during novelty-seeking behavior in which novelty had no extrinsic reward value. Instead, high channel-count electrophysiological experiments and anatomical tracing identified a prominent source of control signals for novelty seeking in the anterior ventral medial temporal cortex (AVMTC), a brain region known to be crucially involved in visual processing and object memory. In addition to their well-known function in signaling the novelty or familiarity of objects in the current environment, AVMTC neurons reflected the predictions of future novel objects, akin to the way neurons in reward-circuitry predict future rewards in order to control reward-seeking. Our data uncover a network of primate brain areas that regulate novelty-seeking. The behavioral and neural distinctions between novelty-seeking and reward-processing highlight how the brain can accomplish behavioral flexibility, providing a mechanism to explore novel objects.

neuroscience↗