Thyroid hormone remodels cortex to coordinate body-wide metabolism and exploration.

Animals adapt to environmental conditions by modifying the function of their internal organs, including the brain. To be adaptive, alterations in behavior must be coordinated with the functional state of organs throughout the body. Here, we find that thyroid hormone-a regulator of metabolism in many peripheral organs-directly activates cell-type-specific transcriptional programs in the frontal cortex of adult male mice. These programs are enriched for axon-guidance genes in glutamatergic projection neurons, synaptic regulatory genes in both astrocytes and neurons, and pro-myelination factors in oligodendrocytes, suggesting widespread plasticity of cortical circuits. Indeed, whole-cell electrophysiology revealed that thyroid hormone alters excitatory and inhibitory synaptic transmission, an effect that requires thyroid hormone-induced gene regulatory programs in presynaptic neurons. Furthermore, thyroid hormone action in the frontal cortex regulates innate exploratory behaviors and causally promotes exploratory decision-making. Thus, thyroid hormone acts directly on the cerebral cortex in males to coordinate exploratory behaviors with whole-body metabolic state.

Top-down control of hippocampal signal-to-noise by prefrontal long-range inhibition.

Prefrontal cortex (PFC) is postulated to exert "top-down control" on information processing throughout the brain to promote specific behaviors. However, pathways mediating top-down control remain poorly understood. In particular, knowledge about direct prefrontal connections that might facilitate top-down control of hippocampal information processing remains sparse. Here we describe monosynaptic long-range GABAergic projections from PFC to hippocampus. These preferentially inhibit vasoactive intestinal polypeptide-expressing interneurons, which are known to disinhibit hippocampal microcircuits. Indeed, stimulating prefrontal-hippocampal GABAergic projections increases hippocampal feedforward inhibition and reduces hippocampal activity in vivo. The net effect of these actions is to specifically enhance the signal-to-noise ratio for hippocampal encoding of object locations and augment object-induced increases in spatial information. Correspondingly, activating or inhibiting these projections promotes or suppresses object exploration, respectively. Together, these results elucidate a top-down prefrontal pathway in which long-range GABAergic projections target disinhibitory microcircuits, thereby enhancing signals and network dynamics underlying exploratory behavior.

An Amygdala Circuit Mediates Experience-Dependent Momentary Arrests during Exploration.

Exploration of novel environments ensures survival and evolutionary fitness. It is expressed through exploratory bouts and arrests that change dynamically based on experience. Neural circuits mediating exploratory behavior should therefore integrate experience and use it to select the proper behavioral output. Using a spatial exploration assay, we uncovered an experience-dependent increase in momentary arrests in locations where animals arrested previously. Calcium imaging in freely exploring mice revealed a genetically and projection-defined neuronal ensemble in the basolateral amygdala that is active during self-paced behavioral arrests. This ensemble was recruited in an experience-dependent manner, and closed-loop optogenetic manipulation of these neurons revealed that they are sufficient and necessary to drive experience-dependent arrests during exploration. Projection-specific imaging and optogenetic experiments revealed that these arrests are effected by basolateral amygdala neurons projecting to the central amygdala, uncovering an amygdala circuit that mediates momentary arrests in familiar places but not avoidance or anxiety/fear-like behaviors.

Humans flexibly integrate social information despite interindividual differences in reward.

There has been much progress in understanding human social learning, including recent studies integrating social information into the reinforcement learning framework. Yet previous studies often assume identical payoffs between observer and demonstrator, overlooking the diversity of social information in real-world interactions. We address this gap by introducing a socially correlated bandit task that accommodates payoff differences among participants, allowing for the study of social learning under more realistic conditions. Our Social Generalization (SG) model, tested through evolutionary simulations and two online experiments, outperforms existing models by incorporating social information into the generalization process, but treating it as noisier than individual observations. Our findings suggest that human social learning is more flexible than previously believed, with the SG model indicating a potential resource-rational trade-off where social learning partially replaces individual exploration. This research highlights the flexibility of humans' social learning, allowing us to integrate social information from others with different preferences, skills, or goals.

Disrupted routines anticipate musical exploration.

Understanding and predicting the emergence and evolution of cultural tastes manifested in consumption patterns is of central interest to social scientists, analysts of culture, and purveyors of content. Prior research suggests that taste preferences relate to personality traits, values, shifts in mood, and immigration destination. Understanding everyday patterns of listening and the function music plays in life has remained elusive, however, despite speculation that musical nostalgia may compensate for local disruption. Using more than one hundred million streams of four million songs by tens of thousands of international listeners from a global music service, we show that breaches in personal routine are systematically associated with personal musical exploration. As people visited new cities and countries, their preferences diversified, converging toward their travel destinations. As people experienced the very different disruptions associated with COVID-19 lockdowns, their preferences diversified further. Personal explorations did not tend to veer toward the global listening average, but away from it, toward distinctive regional musical content. Exposure to novel music explored during periods of routine disruption showed a persistent influence on listeners' future consumption patterns. Across all of these settings, musical preference reflected rather than compensated for life's surprises, leaving a lasting legacy on tastes. We explore the relationship between these findings and global patterns of behavior and cultural consumption.

Space wandering in the rodent default mode network.

The default mode network (DMN) is a large-scale brain network known to be suppressed during a wide range of cognitive tasks. However, our comprehension of its role in naturalistic and unconstrained behaviors has remained elusive because most research on the DMN has been conducted within the restrictive confines of MRI scanners. Here, we use multisite GCaMP (a genetically encoded calcium indicator) fiber photometry with simultaneous videography to probe DMN function in awake, freely exploring rats. We examined neural dynamics in three core DMN nodes-the retrosplenial cortex, cingulate cortex, and prelimbic cortex-as well as the anterior insula node of the salience network, and their association with the rats' spatial exploration behaviors. We found that DMN nodes displayed a hierarchical functional organization during spatial exploration, characterized by stronger coupling with each other than with the anterior insula. Crucially, these DMN nodes encoded the kinematics of spatial exploration, including linear and angular velocity. Additionally, we identified latent brain states that encoded distinct patterns of time-varying exploration behaviors and found that higher linear velocity was associated with enhanced DMN activity, heightened synchronization among DMN nodes, and increased anticorrelation between the DMN and anterior insula. Our findings highlight the involvement of the DMN in collectively and dynamically encoding spatial exploration in a real-world setting. Our findings challenge the notion that the DMN is primarily a "task-negative" network disengaged from the external world. By illuminating the DMN's role in naturalistic behaviors, our study underscores the importance of investigating brain network function in ecologically valid contexts.

Childhood unpredictability and the development of exploration.

Early in development, the process of exploration helps children gather new information that fosters learning about the world. Yet, it is unclear how childhood experiences may influence the way humans approach new learning. What influences decisions to exploit known, familiar options versus trying a novel alternative? We found that childhood unpredictability, characterized by unpredictable caregiving and unstable living environments, was associated with reduced exploratory behavior. This effect holds while controlling for individual differences, including anxiety and stress. Individuals who perceived their childhoods as unpredictable explored less and were instead more likely to repeat previous choices (habitual responding). They were also more sensitive to uncertainty than to potential rewards, even when the familiar options yielded lower rewards. We examined these effects across multiple task contexts and via both in-person (N = 78) and online replication (N = 84) studies among 10- to 13-y-olds. Results are discussed in terms of the potential cascading effects of unpredictable environments on the development of decision-making and the effects of early experience on subsequent learning.

Having multiple selves helps learning agents explore and adapt in complex changing worlds.

Satisfying a variety of conflicting needs in a changing environment is a fundamental challenge for any adaptive agent. Here, we show that designing an agent in a modular fashion as a collection of subagents, each dedicated to a separate need, powerfully enhanced the agent's capacity to satisfy its overall needs. We used the formalism of deep reinforcement learning to investigate a biologically relevant multiobjective task: continually maintaining homeostasis of a set of physiologic variables. We then conducted simulations in a variety of environments and compared how modular agents performed relative to standard monolithic agents (i.e., agents that aimed to satisfy all needs in an integrated manner using a single aggregate measure of success). Simulations revealed that modular agents a) exhibited a form of exploration that was intrinsic and emergent rather than extrinsically imposed; b) were robust to changes in nonstationary environments, and c) scaled gracefully in their ability to maintain homeostasis as the number of conflicting objectives increased. Supporting analysis suggested that the robustness to changing environments and increasing numbers of needs were due to intrinsic exploration and efficiency of representation afforded by the modular architecture. These results suggest that the normative principles by which agents have adapted to complex changing environments may also explain why humans have long been described as consisting of "multiple selves."

Acetylcholine and noradrenaline enhance foraging optimality in humans.

Foraging theory prescribes when optimal foragers should leave the current option for more rewarding alternatives. Actual foragers often exploit options longer than prescribed by the theory, but it is unclear how this foraging suboptimality arises. We investigated whether the upregulation of cholinergic, noradrenergic, and dopaminergic systems increases foraging optimality. In a double-blind, between-subject design, participants (N = 160) received placebo, the nicotinic acetylcholine receptor agonist nicotine, a noradrenaline reuptake inhibitor reboxetine, or a preferential dopamine reuptake inhibitor methylphenidate, and played the role of a farmer who collected milk from patches with different yield. Across all groups, participants on average overharvested. While methylphenidate had no effects on this bias, nicotine, and to some extent also reboxetine, significantly reduced deviation from foraging optimality, which resulted in better performance compared to placebo. Concurring with amplified goal-directedness and excluding heuristic explanations, nicotine independently also improved trial initiation and time perception. Our findings elucidate the neurochemical basis of behavioral flexibility and decision optimality and open unique perspectives on psychiatric disorders affecting these functions.

Exploratory Rearing Is Governed by Hypothalamic Melanin-Concentrating Hormone Neurons According to Locus Ceruleus.

Information seeking, such as standing on tiptoes to look around in humans, is observed across animals and helps survival. Its rodent analog-unsupported rearing on hind legs-was a classic model in deciphering neural signals of cognition and is of intense renewed interest in preclinical modeling of neuropsychiatric states. Neural signals and circuits controlling this dedicated decision to seek information remain largely unknown. While studying subsecond timing of spontaneous behavioral acts and activity of melanin-concentrating hormone (MCH) neurons (MNs) in behaving male and female mice, we observed large MN activity spikes that aligned to unsupported rears. Complementary causal, loss and gain of function, analyses revealed specific control of rear frequency and duration by MNs and MCHR1 receptors. Activity in a key stress center of the brain-the locus ceruleus noradrenaline cells-rapidly inhibited MNs and required functional MCH receptors for its endogenous modulation of rearing. By defining a neural module that both tracks and controls rearing, these findings may facilitate further insights into biology of information seeking.