Curiosity: primate neural circuits for novelty and information seeking.

For many years, neuroscientists have investigated the behavioural, computational and neurobiological mechanisms that support value-based decisions, revealing how humans and animals make choices to obtain rewards. However, many decisions are influenced by factors other than the value of physical rewards or second-order reinforcers (such as money). For instance, animals (including humans) frequently explore novel objects that have no intrinsic value solely because they are novel and they exhibit the desire to gain information to reduce their uncertainties about the future, even if this information cannot lead to reward or assist them in accomplishing upcoming tasks. In this Review, I discuss how circuits in the primate brain responsible for detecting, predicting and assessing novelty and uncertainty regulate behaviour and give rise to these behavioural components of curiosity. I also briefly discuss how curiosity-related behaviours arise during postnatal development and point out some important reasons for the persistence of curiosity across generations.

Lateral entorhinal cortex subpopulations represent experiential epochs surrounding reward.

During goal-directed navigation, 'what' information, describing the experiences occurring in periods surrounding a reward, can be combined with spatial 'where' information to guide behavior and form episodic memories. This integrative process likely occurs in the hippocampus, which receives spatial information from the medial entorhinal cortex; however, the source of the 'what' information is largely unknown. Here, we show that mouse lateral entorhinal cortex (LEC) represents key experiential epochs during reward-based navigation tasks. We discover separate populations of neurons that signal goal approach and goal departure and a third population signaling reward consumption. When reward location is moved, these populations immediately shift their respective representations of each experiential epoch relative to reward, while optogenetic inhibition of LEC disrupts learning the new reward location. Therefore, the LEC contains a stable code of experiential epochs surrounding and including reward consumption, providing reward-centric information to contextualize the spatial information carried by the medial entorhinal cortex.

Curiosity-driven exploration: foundations in neuroscience and computational modeling.

Curiosity refers to the intrinsic desire of humans and animals to explore the unknown, even when there is no apparent reason to do so. Thus far, no single, widely accepted definition or framework for curiosity has emerged, but there is growing consensus that curious behavior is not goal-directed but related to seeking or reacting to information. In this review, we take a phenomenological approach and group behavioral and neurophysiological studies which meet these criteria into three categories according to the type of information seeking observed. We then review recent computational models of curiosity from the field of machine learning and discuss how they enable integrating different types of information seeking into one theoretical framework. Combinations of behavioral and neurophysiological studies along with computational modeling will be instrumental in demystifying the notion of curiosity.

Assessing the exploratory profile of two zebrafish populations: Influence of anxiety-like phenotypes and independent trials on homebase-related parameters and exploration.

Anxiety is a protective behavior when animals face aversive conditions. The open field test (OFT) is used to assess the spatio-temporal dynamics of exploration, in which both homebase formation and recognition of environmental cues may reflect habituation to unfamiliar conditions. Because emotional- and affective-like states influence exploration patterns and mnemonic aspects, we aimed to verify whether the exploratory behaviors of two zebrafish populations showing distinct baselines of anxiety differ in two OFT sessions. Firstly, we assessed the baseline anxiety-like responses of short fin (SF) and leopard (LEO) populations using the novel tank test (NTT) and light-dark test (LDT) in 6-min trials. Fish were later tested in two consecutive days in the OFT, where the spatial occupancy and exploratory profile were analyzed for 30 min. In general, LEO showed pronounced diving behavior and scototaxis in the NTT and LDT, respectively, in which an "anxiety index" corroborated their exacerbated anxiety-like behavior. In the OFT, the SF population spent less time to establish the homebase in the 1st trial, while only LEO showed a markedly reduction in the latency to homebase formation in the 2nd trial. Both locomotion and homebase-related activities were decreased in the 2nd trial, in which animals also revealed increased occupancy in the center area of the apparatus. Moreover, we verified a significant percentage of homebase conservation for both populations, while only SF showed reduced the number of trips and increased the average length of trips. Principal component analyses revealed that distinct factors accounted for total variances between trials for each population tested. While homebase exploration was reduced in the 2nd trial for SF, an increased occupancy in the center area and hypolocomotion were the main factors that contribute to the effects observed in LEO during re-exposure to the OFT. In conclusion, our novel data support the homebase conservation in zebrafish subjected to independent OFT sessions, as well as corroborate a population-dependent effect on specific behavioral parameters related to exploration.

Relationship between boldness and exploratory behavior in adult zebrafish.

Behavioral responses vary between individuals and may be repeated in different contexts over time. When a behavioral response set is linked and present regardless of the context, it characterizes a behavioral syndrome. By evaluating how bold and shy (profiles related to risk-taking) individuals perform about exploration and anxiety, we can predict relationships of behavioral syndromes and better understand how different axis of personality is formed. Here we classified the profiles by risk-taking and evaluated their exploration behavior in the open field test. In this context, the two groups showed significant differences in thigmotaxis behavior: bold individuals habituate faster and show decreased thigmotaxis (less anxiety), while shy ones are less prone to leave the security of the side areas of the open tank and present higher anxiety. We emphasized the importance of further investigating the behavior of these profiles in other contexts and the importance of each one for the evolution and fitness of the species, in addition to a better understanding of which behaviors are involved in the behavioral syndromes in zebrafish.

A change in behavioral state switches the pattern of motor output that underlies rhythmic head and orofacial movements.

The breathing rhythm serves as a reference that paces orofacial motor actions and orchestrates active sensing. Past work has reported that pacing occurs solely at a fixed phase relative to sniffing. We re-evaluated this constraint as a function of exploratory behavior. Allocentric and egocentric rotations of the head and the electromyogenic activity of the motoneurons for head and orofacial movements were recorded in free-ranging rats as they searched for food. We found that a change in state from foraging to rearing is accompanied by a large phase shift in muscular activation relative to sniffing, and a concurrent change in the frequency of sniffing, so that pacing now occurs at one of the two phases. Further, head turning is biased such that an animal gathers a novel sample of its environment upon inhalation. In total, the coordination of active sensing has a previously unrealized computational complexity. This can emerge from hindbrain circuits with fixed architecture and credible synaptic time delays.

The Multifaceted Role of Self-Generated Question Asking in Curiosity-Driven Learning.

Curiosity motivates the search for missing information, driving learning, scientific discovery, and innovation. Yet, identifying that there is a gap in one's knowledge is itself a critical step, and may demand that one formulate a question to precisely express what is missing. Our work captures the integral role of self-generated questions during the acquisition of new information, which we refer to as active-curiosity-driven learning. We tested active-curiosity-driven learning using our "Curiosity Question & Answer Task" paradigm, where participants (N=135) were asked to generate questions in response to novel, incomplete factual statements and provided the opportunity to forage for answers. We also introduce new measures of question quality that express how well questions capture stimulus and foraging information. We hypothesized that active question asking should influence behavior across the stages of our task by increasing the probability that participants express curiosity, forage for answers, and remember what they had thereby discovered. We found that individuals who asked a high number of quality questions experienced elevated curiosity, were more likely to pursue missing information that was semantically related to their questions, and more likely to retain the information on a later cued recall test. Additional analyses revealed that curiosity played a predominant role in motivating participants to forage for missing information, and that both curiosity and satisfaction with the acquired information boosted memory recall. Overall, our results suggest that asking questions enhances the value of missing information, with important implications for learning and discovery of all forms.

Expanding the use of homebase-related parameters to investigate how distinct stressful conditions affect zebrafish behaviors.

Stress is a physiological reaction that allows the organisms to cope with challenging situations daily. Thus, elucidating the behavioral outcomes following different stressors is of great importance in translational research. Here, we aimed to characterize the main factors which explain similarities and differences of two stress protocols on zebrafish exploratory activity. To answer this point, we performed behavioral analyses aiming to simplify the data structure associated with homebase-related measurements in an integrated manner. Adult zebrafish were exposed to conspecific alarm substance for 5 min (acute stress protocol - AS) or submitted to 7 days of unpredictable chronic stress (UCS). Immediately after AS or in the subsequent day following UCS (8th day), fish were individually tested in the open field and the behaviors were recorded for 30 min to posterior identification of homebase locations. For both protocols, behavioral clustering revealed two major clusters, grouping homebase- and locomotor-related parameters, respectively. While AS increased both positive and negative correlations between exploratory and locomotor endpoints, a significant increase in negative correlations was found in UCS-challenged fish. Comparison of the principal component analyses data set revealed a reduced exploratory activity using the homebase in AS group, while decreased locomotion in the periphery and anxiety-like behaviors were evidenced in UCS fish. In conclusion, our findings revealed a different structure of behavior in zebrafish following AS and UCS protocols, supporting the existence of distinct behavioral strategies to cope with acute and chronic stress. Furthermore, we expand the use of homebase-related measurements as a valuable tool to investigate complex behavioral modulations in future translational neuropsychiatry research.

Mouse spontaneous behavior reflects individual variation rather than estrous state.

Behavior is shaped by both the internal state of an animal and its individual behavioral biases. Rhythmic variation in gonadal hormones during the estrous cycle is a defining feature of the female internal state, one that regulates many aspects of sociosexual behavior. However, it remains unclear whether estrous state influences spontaneous behavior and, if so, how these effects might relate to individual behavioral variation. Here, we address this question by longitudinally characterizing the open-field behavior of female mice across different phases of the estrous cycle, using unsupervised machine learning to decompose spontaneous behavior into its constituent elements.1,2,3,4 We find that each female mouse exhibits a characteristic pattern of exploration that uniquely identifies it as an individual across many experimental sessions; by contrast, estrous state only negligibly impacts behavior, despite its known effects on neural circuits that regulate action selection and movement. Like female mice, male mice exhibit individual-specific patterns of behavior in the open field; however, the exploratory behavior of males is significantly more variable than that expressed by females both within and across individuals. These findings suggest underlying functional stability to the circuits that support exploration in female mice, reveal a surprising degree of specificity in individual behavior, and provide empirical support for the inclusion of both sexes in experiments querying spontaneous behaviors.

Behavioral and neural correlates of licking for 66% alcohol in Wistar rats: Caloric balance or sensation/novelty seeking?

Whereas rodents generally reject high alcohol concentrations, access to 66% alcohol can reinforce operant licking in a progressive ratio situation. Three experiments were conducted to identify a potential mechanism underlying this effect. In Experiment 1, food-restricted male and female Wistar rats received access to either 66% alcohol or water in their home cage for one hour over four sessions. Consumption of alcohol and water was similar, showing that rats neither preferred nor rejected 66% alcohol. Peripheral (but not central) activity in an open field (OF) was higher after access to 66% alcohol than water, a result inconsistent with motor impairment. Blood alcohol concentration was higher after 66% alcohol than water and was positively correlated with fluid displacement and peripheral distance in the OF. c-Fos immunoreactivity after exposure to 66% alcohol vs. water showed increased activation in the nucleus accumbens shell, anterior cingulate cortex, and insular cortex. In Experiment 2, whether access to food was restricted (to an 81-84% of the ad libitum weight) or free (ad libitum), female Wistar rats licked at similar frequency from a sipper tube delivering 66% alcohol. This result is inconsistent with an account based on the caloric content of 66% alcohol. In Experiment 3, food-restricted male and female Wistar rats exhibited a positive correlation between activity in the central area of an OF (an index of sensation/novelty seeking) and licking for 66% alcohol. These results are consistent with the hypothesis that the reinforcing value of 66% alcohol is related to sensation/novelty seeking.

Curiosity: The effects of feedback and confidence on the desire to know.

In 10 experiments, we investigated the relations among curiosity and people's confidence in their answers to general information questions after receiving different kinds of feedback: yes/no feedback, true or false informational feedback under uncertainty, or no feedback. The results showed that when people had given a correct answer, yes/no feedback resulted in a near complete loss of curiosity. Upon learning they had made an error via yes/no feedback, curiosity increased, especially for high-confidence errors. When people were given true feedback under uncertainty (they were given the correct answer but were not told that it was correct), curiosity increased for high-confidence errors but was unchanged for correct responses. In contrast, when people were given false feedback under uncertainty, curiosity increased for high-confidence correct responses but was unchanged for errors. These results, taken as a whole, are consistent with the region of proximal learning model which proposes that while curiosity is minimal when people are completely certain that they know the answer, it is maximal when people believe that they almost know. Manipulations that drew participants toward this region of "almost knowing" resulted in increased curiosity. A serendipitous result was the finding (replicated four times in this study) that when no feedback was given, people were more curious about high-confidence errors than they were about equally high-confidence correct answers. It was as if they had some knowledge, tapped selectively by their feelings of curiosity, that there was something special (and possibly amiss) about high-confidence errors. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Responses to environmental enrichment are associated with personality characteristics in chestnut-bellied seed finches (Sporophila angolensis).

Environmental enrichment (EE) is used to promote natural behaviours in captive animals and may hold promise as a form of pre-release training, a strategy for improving coping skills of translocated birds. We investigated the use of EE to enhance foraging and vigilance behaviours of captive Sporophila angolensis, which may be related to post-release survival. We also evaluated whether consistent individual behavioural differences affected birds' responses to EE. We submitted 19 captive seed-finches to three short-term challenges: tonic immobility (TI), new environment (NE) and new object (NO) tests. TI behaviour is related to fear/escape response to potential predators and novelty tests (NE and NO) assess neophobia, which are ecologically relevant personality traits influencing the shyness-boldness continuum. We noted a pronounced variability among the individuals' personality traits, both in their fear and escape-related responses in the TI test and along shy/bold z-scores in NE and NO tests. During a period of enrichment, birds spent more time foraging and less time in vigilance states compared with both control phases. Personality traits of the birds affected their responses to enrichment with bolder birds spending more time foraging. The EE-related decrease in vigilance was independent of the birds' personality traits. Our findings highlight interactions between personality and rearing environment that may impact post-release outcomes for translocated animals.

Temozolomide treatment inhibits spontaneous motivation for exploring a complex object in mice: A potential role of adult hippocampal neurogenesis in "curiosity".

Intrinsic exploratory biases are an innate motivation for exploring certain types of stimuli or environments over others, and they may be associated with cognitive, emotional, and even personality-like traits. However, their neurobiological basis has been scarcely investigated. Considering the involvement of the hippocampus in novelty recognition and in spatial and pattern separation tasks, this work researched the role of adult hippocampal neurogenesis (AHN) in intrinsic exploratory bias for a perceptually complex object in mice. Spontaneous object preference tasks revealed that both male and female C57BL/6J mice showed a consistent unconditioned preference for exploring "complex"-irregular-objects over simpler ones. Furthermore, increasing objects' complexity resulted in an augmented time of object exploration. In a different experiment, male mice received either vehicle or the DNA alkylating agent temozolomide (TMZ) for 4 weeks, a pharmacological treatment that reduced AHN as evidenced by immunohistochemistry. After assessment in a behavioral test battery, the TMZ-treated mice did not show any alterations in general exploratory and anxiety-like responses. However, when tested in the spontaneous object preference task, the TMZ-treated mice did not display enhanced exploration of the complex object, as evidenced both by a reduced exploration time-specifically for the complex object-and a lack of preference for the complex object over the simple one. This study supports a novel role of AHN in intrinsic exploratory bias for perceptual complexity. Moreover, the spontaneous complex object preference task as a rodent model of "curiosity" is discussed.

Rat's response to a novelty and increased complexity of the environment resulting from the introduction of movable vs. stationary objects in the free exploration test.

Most animals, including rats, show a preference for more complex environments. This is demonstrated particularly well when complexity increases due to the addition of new elements to the environment. The aim of the study was to investigate the reaction to novelty, understood as a change in environmental properties that involve both changes in complexity and controllability. Controllability may allow for dealing with challenges of an environment of low predictability in a way that the animal's own activity reduces the uncertainty of environmental events. In our study, the animals underwent a spontaneous exploration test in low-stress conditions. After a period of habituation to the experimental arena, additional stationary (increased complexity) and/or movable (increased complexity and controllability) tunnels were introduced, and the reaction of the rats to the novel objects was measured. The results of the study confirmed that an increase in the complexity of the environment through the addition of objects triggers a more intensive exploratory activity in rats. However, an increased spatial complexity combined with the movability of the novel objects seems to result in increased caution towards the novelty after an initial inspection of the changed objects. It suggests that the complexity of the novelty may trigger both neophilia and neophobia depending on the level of the predictability of the novel environment and that the movability of newly introduced objects is not independent of other parameters of the environment.

Rats use strategies to make object choices in spontaneous object recognition tasks.

Rodent spontaneous object recognition (SOR) paradigms are widely used to study the mechanisms of complex memory in many laboratories. Due to the absence of explicit reinforcement in these tasks, there is an underlying assumption that object exploratory behaviour is 'spontaneous'. However, rodents can strategise, readily adapting their behaviour depending on the current information available and prior predications formed from learning and memory. Here, using the object-place-context (episodic-like) recognition task and novel analytic methods relying on multiple trials within a single session, we demonstrate that rats use a context-based or recency-based object recognition strategy for the same types of trials, depending on task conditions. Exposure to occasional ambiguous conditions changed animals' responses towards a recency-based preference. However, more salient and predictable conditions led to animals exploring objects on the basis of episodic novelty reliant on contextual information. The results have important implications for future research using SOR tasks, especially in the way experimenters design, analyse and interpret object recognition experiments in non-human animals.

Decrease in the rewarding value of spatial novelty due to the contamination of the stimulus field with light - Evidence from a free exploration test involving rats.

It has been shown that rearranging the spatial properties of a familiar environment consistently elicits a positive response in rats directed toward the source of novelty. Previous studies have been conducted under red light or darkness. The purpose of this study was to test the effect of rearranging the spatial properties of a familiar environment in conjunction with a change in lighting conditions. The results have shown specific effects of the light presence and its intensity on different behavioral measures. We propose that this study provides a basis for hypothesizing a two-way mechanism of the behavioral response to light regulation in rats. The first is based on ON/OFF states. This level may be related to fundamental, evolutionarily early, emergent components of behavioral antipredator adaptations. Another level of behavioral regulation involves mechanisms sensitive to light intensity. These appear to be involved in the regulation of more advanced behavioral acts, such as exploratory responses. This may suggest that light intensity analysis may require the involvement of more advanced cognitive components in the behavioral regulation system.

Age-related loss of recognition memory and its correlation with hippocampal and perirhinal cortex changes in female Sprague Dawley rats.

Ageing is associated with impaired performance in recognition memory, a process that consists of the discrimination of familiar and novel stimuli. Previous studies have shown the impact of ageing on object recognition memories. However, the early stages of memory impairment remain unknown. To fill this gap, we aimed at evaluating the ability of young (Y), middle-aged (MA), and senile (S) female Sprague-Dawley rats to retain 24 h long-term recognition memory. The MA cohort was included to characterise early memory deficits under two behavioural paradigms based on spontaneous location recognition (SLR) and spontaneous object recognition (SOR) tasks. In the SLR task, there was a markedly diminished novel discrimination capacity in the MA and S rats compared with the Y ones. In the SOR task, S rats evidenced a deterioration in novelty discrimination, while MA rats partially preserved the capacity to distinguish the new stimulus as compared with Y rats. Regarding early changes from MA to S rats, immunohistochemistry showed a marked decrease in the number and diameter of adult-born immature neurons in the Dentate Gyrus (DG) with a positive correlation with behavioural performance in the SLR task. Furthermore, we found a slight reduction in CA3 mature neurons and a decrease in the number of total microglia in the perirhinal cortex (Prh) in MA and S rats as compared with Y rats. As regards changes that were only observed in S rats, we found an increase in the number of total and reactive microglia in CA3 and a reduction in the number of total microglia in the DG. We conclude that spatial discrimination capacity could be affected earlier than feature discrimination capacity. We suggest that early depletion of neurogenesis in MA rats is involved in object location recognition deficits, whereas the disruption of microglial homeostasis in the Prh could be associated with object feature discrimination capacity.

Influence of acute and unpredictable chronic stress on spatio-temporal dynamics of exploratory activity in zebrafish with emphasis on homebase-related behaviors.

The open field is a suitable task to analyze the sequential organization of exploratory activity and the homebase formation represents an important feature of environmental recognition. Although the zebrafish can define homebase locations, there are no data reporting how stressful conditions modulate complex behaviors of this aquatic species in the open field so far. Here, we aimed to characterize the spatio-temporal exploratory activity of adult zebrafish in the open field test, as well as to verify the responsiveness of homebase-related parameters to acute stress (AS) and unpredictable chronic stress (UCS) protocols. Animals were exposed to conspecific alarm substance for 5 min or subjected to a 7-days stress protocol using distinct stressors in an unpredictable manner. Immediately after exposure to AS or 24 h after UCS, fish were individually placed in a circular tank and their behaviors were recorded for 30 min to identify the respective homebase for each animal. We observed that UCS, but not AS, increased thigmotaxis compared to the non-stressed fish. Notably, the sequential organization of exploratory activity showed robust differences depending on the stress protocol. After the first 15 min of trial, AS-challenged fish apparently used the homebase to organize briefly explorations to the environment. Conversely, the UCS group was more immobile in the homebase after periodically performing 'swimming bursts' to the periphery with a greater number of stops per trip. Physiological stress responses were confirmed by the increased whole-body cortisol in both AS and UCS groups. In conclusion, our novel findings report a different exploratory profile related to stress responses in adult zebrafish tested in the open field, supporting the sensitivity of homebase-related parameters to manipulations that modulate affective-like states.

Novelty and uncertainty regulate the balance between exploration and exploitation through distinct mechanisms in the human brain.

Both novelty and uncertainty are potent features guiding exploration; however, they are often experimentally conflated, and an understanding of how they interact to regulate the balance between exploration and exploitation has proved elusive. Using a task designed to decouple the influence of novelty and uncertainty, we identify separable mechanisms through which exploration is directed. We show that uncertainty-directed exploration is sensitive to the prospective benefit offered by new information, whereas novelty-directed exploration is maintained regardless of its potential advantage. Using a computational framework in conjunction with fMRI, we show that uncertainty-directed choice is rooted in an adaptive bias indexing the prospective utility of exploration. In contrast, novelty persistently promotes exploration by optimistically inflating reward expectations while simultaneously dampening uncertainty signals. Our results identify separable neural substrates charged with balancing the explore/exploit trade-off to foster a manageable decomposition of an otherwise intractable problem.

Abnormal sensory perception masks behavioral performance of Grin1 knockdown mice.

The development and function of sensory systems require intact glutamatergic neurotransmission. Changes in touch sensation and vision are common symptoms in autism spectrum disorders, where altered glutamatergic neurotransmission is strongly implicated. Further, cortical visual impairment is a frequent symptom of GRIN disorder, a rare genetic neurodevelopmental disorder caused by pathogenic variants of GRIN genes that encode NMDA receptors. We asked if Grin1 knockdown mice (Grin1KD), as a model of GRIN disorder, had visual impairments resulting from NMDA receptor deficiency. We discovered that Grin1KD mice had deficient visual depth perception in the visual cliff test. Since Grin1KD mice are known to display robust changes in measures of learning, memory, and emotionality, we asked whether deficits in these higher-level processes could be partly explained by their visual impairment. By changing the experimental conditions to improve visual signals, we observed significant improvements in the performance of Grin1KD mice in tests that measure spatial memory, executive function, and anxiety. We went further and found destabilization of the outer segment of retina together with the deficient number and size of Meissner corpuscles (mechanical sensor) in the hind paw of Grin1KD mice. Overall, our findings suggest that abnormal sensory perception can mask the expression of emotional, motivational and cognitive behavior of Grin1KD mice. This study demonstrates new methods to adapt routine behavioral paradigms to reveal the contribution of vision and other sensory modalities in cognitive performance.