Novelty Exploration Research Articles

Remote islands as natural laboratories: human-food association increases attraction to humans and novelty exploration in a seabird.

Increased attraction to humans and their objects often arises after repeated and positive human-wildlife encounters (e.g. food provided in tourist settings). The causes of this 'over-attraction', which may result from a learned association between humans and food, are still poorly studied in wild animals. Understanding the influence of humans on animals' responses is yet crucial to prevent negative effects (e.g. aggression). We presented three novel objects to two groups of free-ranging brown skuas (Catharacta antarctica ssp. lonnbergi) in the remote sub-Antarctic, where their habitats show no or minimal human disturbance. Skuas in one group (Verte) had previously participated in repeated food-rewarded behavioural and cognitive tasks with a human experimenter; skuas in the other group (Ratmanoff) had never done so. Objects consisted of (i) one natural-food-resembling object (plastic fish), (ii) one anthropogenic food object (real cake slice), and (iii) one anthropogenic non-food object (yellow glove). Verte group skuas approached the human experimenter and pecked significantly more and sooner at novel objects. Human-food association may have thus resulted in increased attraction to humans and novelty exploration in previously naive brown skuas, making this species a useful model for investigating the consequences of experience with humans on wildlife behaviour.

Mismatch novelty exploration training shifts VPAC1 receptor-mediated modulation of hippocampal synaptic plasticity by endogenous VIP in male rats.

Novelty influences hippocampal-dependent memory through metaplasticity. Mismatch novelty detection activates the human hippocampal CA1 area and enhances rat hippocampal-dependent learning and exploration. Remarkably, mismatch novelty training (NT) also enhances rodent hippocampal synaptic plasticity while inhibition of VIP interneurons promotes rodent exploration. Since VIP, acting on VPAC1 receptors (Rs), restrains hippocampal LTP and depotentiation by modulating disinhibition, we now investigated the impact of NT on VPAC1 modulation of hippocampal synaptic plasticity in male Wistar rats. NT enhanced both CA1 hippocampal LTP and depotentiation unlike exploring an empty holeboard (HT) or a fixed configuration of objects (FT). Blocking VIP VPAC1Rs with PG 97269 (100 nM) enhanced both LTP and depotentiation in naïve animals, but this effect was less effective in NT rats. Altered endogenous VIP modulation of LTP was absent in animals exposed to the empty environment (HT). HT and FT animals showed mildly enhanced synaptic VPAC1R levels, but neither VIP nor VPAC1R levels were altered in NT animals. Conversely, NT enhanced the GluA1/GluA2 AMPAR ratio and gephyrin synaptic content but not PSD-95 excitatory synaptic marker. In conclusion, NT influences hippocampal synaptic plasticity by reshaping brain circuits modulating disinhibition and its control by VIP-expressing hippocampal interneurons while upregulation of VIP VPAC1Rs is associated with the maintenance of VIP control of LTP in FT and HT animals. This suggests VIP receptor ligands may be relevant to co-adjuvate cognitive recovery therapies in aging or epilepsy, where LTP/LTD imbalance occurs.

Exploration of Novelty as Part of the Player Experience of Need Satisfaction in Games

Abstract Need for novelty has been proposed as a potential candidate to be a basic psychological need, in addition to autonomy, competence, and relatedness in the Self-Determination Theory literature. In this paper, we investigate the need for novelty in the video gaming domain, and examine whether it differentiates as a distinct construct from the other three basic needs of autonomy, competence and relatedness. To be able to test this, we examined whether novelty uniquely predicts context specific outcomes, such as concentration, satisfaction and commitment in games. We conducted an online survey with 390 online video game players. Regression analyses showed that need for novelty indeed emerges as a distinct construct, and uniquely predicts positive outcomes. This study provides initial support for novelty as a basic psychological need that is needed for players' intrinsic motivation, and shows the importance of novelty in online video gaming. We discuss new avenues for research related to need for novelty and how consideration of novelty may impact game design.

Responses to novelty in wild insular birds: comparing breeding populations in ecologically contrasting habitats

Islands have always provided ideal natural laboratories for assessing ecological parameters influencing behaviour. One hypothesis that lends itself well to testing in island habitats suggests that animals frequenting highly variable environments should be motivated to approach and interact with (i.e. explore) novelty. Intra-species comparisons of populations living in ecologically different island habitats may, thus, help reveal the factors that modulate animals’ responses to novelty. In this study, we presented novel objects to two geographically isolated breeding populations of the black-faced sheathbill (Chionis minor), a sedentary land-based bird that frequents remote sub-Antarctic islands. In the first population (Chionis minor ssp. crozettensis), the “Crozet group” (Baie du Marin, Ile de la Possession, Crozet Islands), breeding pairs inhabit a variable habitat close to penguin (Aptenodytes patagonicus) colonies. In the second population (Chionis minor ssp. minor), the “Kerguelen group” (île Verte, Morbihan gulf, Kerguelen Islands) breeding pairs live in penguin-free territories. In this latter population, the environment is less variable due to the presence of a broad intertidal zone which ensures year-round food availability. At both Kerguelen and Crozet, at least one breeding partner in all pairs approached at least one of the novel objects, and we found no significant differences in the latency of approach between the two populations. However, sheathbills at Crozet touched objects significantly more than birds at Kerguelen, and were also faster to touch them. We discuss how environmental variability, along with other potential influencing factors, may favour exploration of novelty in this wild insular bird.

Boredom, sport, and games

ABSTRACT The philosophical literature on sport and games has had little to say about boredom beyond presuming that sports and games can be important ways of overcoming or preventing it. But boredom is an interesting and often misunderstood phenomenon with overlooked implications in this context. Boredom has significant human value and motivates play in ways that contribute to well-being and culture, often through encouraging engaged agency and exploration of novelty. Understanding boredom can also help to clarify problems and tendencies in sports and games that qualify them as havens from boredom.

The Role of Umwelt in Animal Curiosity: A Within and Between Species Comparison of Novelty Exploration in Mongooses

In its broadest sense, curiosity has been described as an intrinsic motivation to acquire novel information; this ‘novelty-seeking’ is notably in the absence of any immediate reward. One way to examine information seeking in animals, has been to present animals with novel objects and measure the way animals gather information through exploration. While this is a standardized and common paradigm, few studies have focused on what factors influence how animals perceive novelty, whilst considering the predicted impacts of an animal’s ‘umwelt’ on exploration. In this study we assessed explorative behaviors in mongooses through both an intra and interspecific view. First, in meerkats (Suricata suricatta) tested in their natural environment, we established that they distinguish familiar from unfamiliar and show increased exploration of novel objects. We also found that odor influenced the meerkats’ explorative action, so that non-odorous items were manipulated longer. Presence of conspecifics influenced approaches to novelty, but not the exploration per se. Human presence interacted with an individual’s level of habituation to impact approaches and exploration of novelty and we found a strong captivity effect on exploration between captive and wild meerkats. Between species analysis showed that yellow mongooses (Cynictis penicillate), a less social mongoose than meerkats, showed higher levels of novelty exploration, when tested within the same habitat. Thus, these findings show that multiple factors, including perceptual abilities (merkwelt) and social factors (sozialwelt), are decisive for when and how animals explore their environment and must be considered both when designing novelty paradigm tests and their interpretations.

Novelty-induced memory consolidation is accompanied by increased Agap3 transcription: a cross-species study

Novelty-induced memory consolidation is a well-established phenomenon that depends on the activation of a locus coeruleus-hippocampal circuit. It is associated with the expression of activity-dependent genes that may mediate initial or cellular memory consolidation. Several genes have been identified to date, however, to fully understand the mechanisms of memory consolidation, additional candidates must be identified. In this cross-species study, we used a contextual novelty-exploration paradigm to identify changes in gene expression in the dorsal hippocampus of both mice and rats. We found that changes in gene expression following contextual novelty varied between the two species, with 9 genes being upregulated in mice and 3 genes in rats. Comparison across species revealed that ArfGAP with a GTPase domain, an ankyrin repeat and PH domain 3 (Agap3) was the only gene being upregulated in both, suggesting a potentially conserved role for Agap3. AGAP3 is known to regulate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptor trafficking in the synapse, which suggests that increased transcription of Agap3 may be involved in maintaining functional plasticity. While we identified several genes affected by contextual novelty exploration, we were unable to fully reverse these changes using SCH 23390, a dopamine D1/D5 receptor antagonist. Further research on the role of AGAP3 in novelty-induced memory consolidation could lead to better understanding of this process and guide future research.

Rewarded Maze Training Increases Approach Behavior in Rats Through Neurogenesis-Dependent Growth of Ventral Hippocampus–Prelimbic Circuits

BackgroundLearning complex navigation routes increases hippocampal volume in humans, but it is not clear whether this growth impacts behaviors outside the learning situation or what cellular mechanisms are involved. MethodsWe trained rats with pharmacogenetic suppression of adult neurogenesis and littermate controls in 3 mazes over 3 weeks and tested novelty approach behavior several days after maze exposure. We then measured hippocampus and prelimbic cortex volumes using magnetic resonance imaging and assessed neuronal and astrocyte morphology. Finally, we investigated the activation and behavioral role of the ventral CA1 (vCA1)-to-prelimbic pathway using immediate-early genes and DREADDs (designer receptors exclusively activated by designer drugs). ResultsMaze training led to volume increase of both the vCA1 region of the hippocampus and the prelimbic region of the neocortex compared with rats that followed fixed paths. Growth was also apparent in individual neurons and astrocytes in these 2 regions, and behavioral testing showed increased novelty approach in maze-trained rats in 2 different tests. Suppressing adult neurogenesis prevented the effects on structure and approach behavior after maze training without affecting maze learning itself. The vCA1 neurons projecting to the prelimbic area were more activated by novelty in maze-trained animals, and suppression of this pathway decreased approach behavior. ConclusionsRewarded navigational learning experiences induce volumetric and morphologic growth in the vCA1 and prelimbic cortex and enhance activation of the circuit connecting these 2 regions. Both the structural and behavioral effects of maze training require ongoing adult neurogenesis, suggesting a role for new neurons in experience-driven increases in novelty exploration.

Selective M5 muscarinic acetylcholine receptor negative allosteric modulator VU6008667 blocks acquisition of opioid self-administration

Recent evidence suggests that inhibition of the M5 muscarinic acetylcholine receptor (mAChR) may provide a novel non-opioid mechanism for the treatment of opioid use disorder (OUD). Previous studies from our group and others have demonstrated that acute administration of the long-acting M5 negative allosteric modulator (NAM) ML375 attenuates established self-administration of cocaine, ethanol, oxycodone, and remifentanil in rats. In the present study, we characterized the effects of acute and repeated administration of the novel, short-acting M5 NAM VU6008667 on the reinforcing effects of oxycodone and reinstatement of oxycodone-seeking behaviors in male Sprague-Dawley rats, as well as on physiological withdrawal from oxycodone. Acute VU6008667 decreased oxycodone self-administration under both fixed ratio 3 (FR3) and progressive ratio (PR) schedules of reinforcement and attenuated cue-induced reinstatement of lever pressing following extinction from oxycodone self-administration, a commonly used relapse model. When administered daily to opioid-naïve rats, VU6008667 prevented acquisition of oxycodone self-administration behavior. VU6008667 had minimal effects on naloxone-precipitated withdrawal. After acute administration, VU6008667 did not inhibit sucrose self-administration and, when given chronically, delayed but did not prevent acquisition of sucrose maintained self-administration. VU6008667 also did not impact oxycodone induced anti-nociception or motor coordination, but mildly decreased novelty exploration. Finally, acute or daily VU6008667 administration did not impair cued fear conditioning. Overall, these results suggest that inhibition of the M5 mAChR may provide a novel, non-opioid based treatment for distinct aspects of OUD by inhibiting opioid intake in established OUD, reducing relapse during abstinence, and by reducing the risk of developing OUD.

Substantia nigra integrity is associated with poorer recognition memory for novel stimuli in early Alzheimer’s disease

AbstractBackgroundThe substantia nigra/ventral tegmental area (SN/VTA), the brain’s most prominent dopamine source, is involved in novelty exploration and episodic memory. Using a novelty detection task combined with neuromelanin‐sensitive MRI, this work aimed to investigate the relationship between SN integrity, neural novelty response and subsequent recognition memory performance in individuals with early Alzheimer’s disease.Method79 healthy subjects, 54 participants with subjective cognitive decline (SCD), 18 with mild cognitive impairment (MCI), and 10 individuals with ADD from the DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study performed a previously published scene novelty and encoding task (“FADE”) using 3T fMRI. Additional 3D T1‐weighted FLASH images were collected to visualize and quantify the volume and MRI contrast in the SN.Linear regression models were generated to assess for associations between either SN volume and median MRI contrast, considered as proxy integrity measures, with functional activity during novelty and subsequent recognition memory performance (dprime). We used site, gender, age and years of education as covariates. We assessed AD pathology in a subsample of individuals with CSF biomarkers (n = 71).ResultWe observed a significant decline in SN volume (p = 0.003) but not MRI contrast in ADD compared to healthy controls. The SN volume in the whole sample correlated positively with recognition memory for novel stimuli (r = 0.35; p = 0.02,). This association held in the CSF subsample (r = 0.31; p = 0.034) and also after correcting for levels of both tau (phosphotau, r = 0.57; p = 0.0284,) and amyloid (Abeta 42/40 ratio, r = 0.46; p = 0.03,). Additionally, SN median MRI contrast significantly correlated with novelty responses in the hippocampus in the CSF subsample and also in amyloid positive but not negative (Abeta 42/40 ratio<0.08, n = 26) individuals. Finally, recognition memory (p<0.001) was significantly decreased in Abeta positive compared to negative individuals.ConclusionWe show that significant degeneration to the SN in AD dementia and pathological Abeta 42/40 levels are associated with poorer recognition memory for novel stimuli. Moreover, associations between SN median MRI contrast and novelty responses differed between amyloid positive and negative individuals. These results indicate that degeneration to the SN may contribute to memory dysfunction in AD dementia which may be linked to pathological amyloid levels.

Local production of corticotropin-releasing hormone in prefrontal cortex modulates male-specific novelty exploration

Neuromodulatory substances can be released from distal afferents for communication between brain structures or produced locally to modulate neighboring circuit elements. Corticotropin-releasing hormone (CRH) from long-range neurons in the hypothalamus projecting to the medial prefrontal cortex (mPFC) has been shown to induce anxiety-like behaviors. However, the role of CRH produced in the mPFC has not been investigated. Here we demonstrate that a specific class of mPFC interneurons that express CRH (CrhINs) releases CRH upon high-frequency stimulation to enhance excitability of layer 2/3 pyramidal cells (L2/3 PCs) expressing the CRH receptors. When stimulated at low frequency, CrhINs release GABA resulting in the inhibition of oxytocin receptor-expressing interneurons (OxtrINs) and L2/3 PCs. Conditional deletion of CRH in mPFC CrhINs and chemogenetic activation of CrhINs have opposite effects on novelty exploration in male but not in female mice, and do not affect anxiety-related behaviors in either males or females. Our data reveal that CRH produced by local interneurons in the mPFC is required for sex-specific novelty exploration and suggest that our understanding of complex behaviors may require knowledge of local and remote neuromodulatory action.

Structural and metabolic activity differences in serotonergic cell groups in a rat model of individual differences of emotionality and stress reactivity

Serotonin regulates a diverse set of functions, including emotional behavior, cognition, sociability, appetite, and sleep. Serotonin is also a key trophic factor that shapes neurodevelopmental processes. Genetic and environmental factors that drive individual differences in the serotonergic system have the capacity to impact brain structure and behavior, and likely contribute to pathophysiological processes involved in neuropsychiatric disorders. Using adult rats selectively bred for low novelty exploration (Low Responders, LR), we previously demonstrated pronounced increases in the levels of their anxiety- and depression- relevant behaviors as compared to the selectively bred High Novelty Responder (HR) rats. These behavioral differences were accompanied by alterations in the expression of genes that regulate serotonin synthesis in the brainstem, and its signaling in the forebrain. The present study extends these observations with a focus on the organization and the metabolism of brainstem serotonin cell groups that provide serotonergic innervation of the hippocampus and other limbic regions of male HR/LR rats. Using design-based stereology, we found the median raphe (MnR) in adult male LR rats contains increased number of serotonergic neurons as compared to the HRs. This is preceded by an increase in the metabolic activity of the caudal dorsal raphe (DRC) and the intrafascicular DR (DRI) during early postnatal development. These findings suggest that structural and functional differences in the raphe-limbic projections shape behavioral inhibition throughout the lifespan.

α7 nicotinic acetylcholine receptor modulation of accumbal dopamine release covaries with novelty seeking.

Heightened novelty-seeking phenotypes are associated with a range of behavioural traits including susceptibility to drug use. These relationships are recapitulated in preclinical models, where rats that exhibit increased exploratory activity in novel environments (high responders-HR) acquire self-administration of psychostimulants more rapidly compared to rats that display low novelty exploration (low responders-LR). Dopamine release dynamics in the nucleus accumbens (NAc) covaries with response to novelty, and differences in dopaminergic signalling are thought to be a major underlying driver of the link between novelty seeking and drug use vulnerability. Accumbal dopamine release is controlled by local microcircuits including modulation through glutamatergic and nicotinic acetylcholine receptor (nAChR) systems, but whether these mechanisms contribute to disparate dopamine signalling across novelty phenotypes is unclear. Here, we used ex vivo voltammetry in the NAc of rats to determine if α7 nAChRs contribute to differential dopamine dynamics associated with individual differences in novelty exploration. We found that blockade of α7 nAChRs attenuates tonic dopamine release evoked by low-frequency stimulations across phenotypes but that phasic release is decreased in LRs while HRs are unaffected. These stimulation frequency- and phenotype-dependent effects result in a decreased dynamic range of release exclusively in LRs. Furthermore, we found that differential α7 modulation of dopamine release in LRs is dependent on AMPA but not NMDA receptors. These results help to form an understanding of the local NAc microcircuitry and provide a potential mechanism for covariance of dopamine dynamics and sensitivity to the reinforcing effects of drugs of abuse.

Novelty exposure induces stronger sensorimotor representations during a manual adaptation task.

Active exploration of novel spatial environments enhances memory for subsequently presented explicit, declarative information in humans. These effects have been attributed to novelty promoting dopamine release via mesolimbic dopaminergic pathways in the brain. As procedural motor learning has been linked to dopamine as well, we predict that novelty effects extend to this domain. To test this hypothesis, the present study examined whether spatial novelty exploration benefits subsequent sensorimotor adaptation. Participants explored either two different virtual environments (i.e., novelty condition; n = 210) or two identical environments (i.e., familiar condition; n = 253). They then performed a manual adaptation task in which they had to adapt joystick movements to a visual perturbation. We assessed the rate of adaptation following the introduction of this perturbation, and the rate of deadaptation following its removal. While results showed reliable adaptation patterns and similar adaptation rates across both conditions, individuals in the novelty condition showed slower deadaptation. This suggests that exposure to spatial novelty induced stronger sensorimotor representations during adaptation, potentially through novelty‐induced dopaminergic effects in mesocortical and/or nigrostriatal pathways. Novelty exposure may be employed to promote motor learning on tasks that require precision movements in altered sensory contexts, for example, in astronauts moving in microgravity or patients with impaired motor processing.

Unfolding of spatial representation at systems level in infant rats.

Spatial representations enable navigation from early life on. However, the brain regions essential to form spatial representations, like the hippocampus, are considered functionally immature before weaning. Here, we examined the formation of representations of space in rat pups on postnatal day (PD) 16, using a simple habituation paradigm where the pups were exposed to an arena on three occasions, separated by ~140 min. Whereas on the first two occasions the arena was the same, on the third "test" occasion either proximal cues (Prox group), or distal cues (Dist group), or proximal and distal cues (Prox-Dist group), or no cues (No-change group) were rearranged. Locomotion (distance traveled) was used as behavioral measure of habituation, and c-Fos expression to measure regional brain activity at test. Locomotion generally decreased across the first two occasions. At test, it reached a minimum in the No-change group, indicating familiarity with the spatial conditions. By contrast, the Prox-Dist group displayed a significant increase in locomotion which was less robust in the Prox group and absent in the Dist group, a pattern suggesting that the pups relied more on proximal than distal cues during spatial exploration. c-Fos activity in the No-change group was significantly suppressed in the hippocampus (CA1, CA3, dentate gyrus) but simultaneously enhanced in the prelimbic area (PL) of the medial prefrontal cortex, compared with untreated Home-cage controls, pointing to a possible involvement of the PL in regulating locomotion in familiar spaces. By contrast, in both Prox-Dist and Prox groups c-Fos activity was enhanced in hippocampal CA1 and CA3 regions, suggesting these regions might be particularly involved in regulating exploration of spatial novelty. Our findings show that functional representations of space at a systems level are formed already in pre-weanling rats.

Visual exploration in adults: Habituation, mere exposure, or optimal level of arousal?

Exploration is one of the most powerful behaviours that drive learning from infancy to adulthood. The aim of the current study was to examine the role of novelty and subjective preference in visual exploration. To do this, we combined a visual exploration task with a subjective evaluation task, presenting novel and familiar pictures. The first goal was to ascertain whether, as demonstrated in babies, short habituation favors visual exploration of familiarity, whereas longer habituation leads to an exploration of novelty. The second goal was to evaluate the influence of familiarization on participants’ subjective evaluation of the stimuli. When presented with novel and very familiar stimuli, participants explored the novel stimuli more. In line with the optimal-level of arousal model, participants showed more positive evaluations of the semi-familiar stimuli compared with very familiar or very novel ones.

Functional Interactions between Entorhinal Cortical Pathways Modulate Theta Activity in the Hippocampus.

Simple SummaryThe activity in the hippocampus is characterized by a strong oscillation at theta frequency that organizes the neuronal firing. We have recently shown that different theta oscillations are present in the hippocampus, opening the possibility to multiple interactions between theta rhythms. In this work, we analyzed the functional connectivity between theta generators during the exploration of a known environment with or without a novel stimulus. The directionality of the interactions was determined using tools based on Granger causality and transfer entropy. We found significant interactions between activity components originated in CA3 and in layers II and III of the entorhinal cortex. During exploration with a novel stimulus, the connectivity from the entorhinal cortex layer II increased, while the influence of CA3 decreased. These results suggest that the entorhinal cortex layer II may drive theta interactions and synchronization in the hippocampus during novelty exploration.Theta oscillations organize neuronal firing in the hippocampus during context exploration and memory formation. Recently, we have shown that multiple theta rhythms coexist in the hippocampus, reflecting the activity in their afferent regions in CA3 (Schaffer collaterals) and the entorhinal cortex layers II (EC-II, perforant pathway) and III (EC-III, temporoammonic pathway). Frequency and phase coupling between theta rhythms were modulated by the behavioral state, with synchronized theta rhythmicity preferentially occurring in tasks involving memory updating. However, information transmission between theta generators was not investigated. Here, we used source separation techniques to disentangle the current generators recorded in the hippocampus of rats exploring a known environment with or without a novel stimulus. We applied analytical tools based on Granger causality and transfer entropy to investigate linear and non-linear directed interactions, respectively, between the theta activities. Exploration in the novelty condition was associated with increased theta power in the generators with EC origin. We found a significant directed interaction from the Schaffer input over the EC-III input in CA1, and a bidirectional interaction between the inputs in the hippocampus originating in the EC, likely reflecting the connection between layers II and III. During novelty exploration, the influence of the EC-II over the EC-III generator increased, while the Schaffer influence decreased. These results associate the increase in hippocampal theta activity and synchrony during novelty exploration with an increase in the directed functional connectivity from EC-II to EC-III.

Dynamics of Neural Microstates in the VTA-Striatal-Prefrontal Loop during Novelty Exploration in the Rat.

Neural activity at the large-scale population level has been suggested to be consistent with a sequence of brief, quasistable spatial patterns. These "microstates" and their temporal dynamics have been linked to myriad cognitive functions and brain diseases. Most of this research has been performed using EEG, leaving many questions, such as the existence, dynamics, and behavioral relevance of microstates at the level of local field potentials (LFPs), unaddressed. Here, we adapted the standard EEG microstate analysis to triple-area LFP recordings from 192 electrodes in rats to investigate the mesoscopic dynamics of neural microstates within and across brain regions during novelty exploration. We performed simultaneous recordings from the prefrontal cortex, striatum, and ventral tegmental area in male rats during awake behavior (object novelty and exploration). We found that the LFP data can be accounted for by multiple, recurring microstates that were stable for ∼60-100 ms. The simultaneous microstate activity across brain regions revealed rhythmic patterns of coactivations, which we interpret as a novel indicator of inter-regional, mesoscale synchronization. Furthermore, these rhythmic coactivation patterns across microstates were modulated by behavioral states such as movement and exploration of a novel object. These results support the existence of a functional mesoscopic organization across multiple brain areas and present a possible link of the origin of macroscopic EEG microstates to zero-lag neuronal synchronization within and between brain areas, which is of particular interest to the human research community.SIGNIFICANCE STATEMENT The coordination of neural activity across the entire brain has remained elusive. Here we combine large-scale neural recordings at fine spatial resolution with the analysis of microstates (i.e., short-lived, recurring spatial patterns of neural activity). We demonstrate that the local activity in different brain areas can be accounted for by only a few microstates per region. These microstates exhibited temporal dynamics that were correlated across regions in rhythmic patterns. We demonstrate that these microstates are linked to behavior and exhibit different properties in the frequency domain during different behavioral states. In summary, LFP microstates provide an insightful approach to studying both mesoscopic and large-scale brain activation within and across regions.

Behavioural tagging: Effect of novelty exploration on plasticity related molecular signatures.

Learning and memory are one of those frontier areas of neurobiology which attract us to investigate the intricacy of this process. Here, we aimed to investigate the general mechanism of "Behavioural Tagging and Capture" in long term memory (LTM) formation and to find the key factors playing role in consolidation of LTM. In this study, we've shown that not only plasticity related proteins (PRPs) but neurotransmitters and immediate early genes (IEGs) also play an important role in memory formation process. It's very well evident that memory traces can last longer if close in time novelty is introduced around memory encoding. Here our results point out that this novelty exploration acts as a modulator in memory consolidation by providing PRPs such as brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), enhancing neurotransmitters (Dopamine), IEGs (cFos) and some enzymes such as acetylcholinesterase (AChE), monoamine oxidase (MAO), sodium-potassium ATPase (Na+K+-ATPase). Therefore, by using a Novel Object Recognition task (NOR) in combination with novel task exposure, we evaluated the role of molecular markers in memory consolidation employing a behavioural tagging model. The purpose of the current study was first to evaluate the effect of novelty exposure around a single trail of NOR task in a critical time window on memory consolidation in rats after 24h and second to determine the expression of BDNF, CREB, c-fos, AChE, MAO, Na+K+-ATPase as potential markers in the medial prefrontal cortex (mPFC) during memory formation. In the present study, to identify and validate the role of these molecular signatures in memory consolidation, infusion of the protein synthesis inhibitor Anisomycin (Ani) was done around the training session that causes a deficit in the formation of LTM when tested 24h after weak encoding. Altogether, here we are providing the first comprehensive set of evidences indicating that BDNF, CREB, dopamine, some enzymes and c-fos role in modulating LTM by employing behavioural tagging model.

Modeling heritability of temperamental differences, stress reactivity, and risk for anxiety and depression: Relevance to research domain criteria (RDoC).

Animal models provide important tools to study biological and environmental factors that shape brain function and behavior. These models can be effectively leveraged by drawing on concepts from the National Institute of Mental Health Research Domain Criteria (RDoC) Initiative, which aims to delineate molecular pathways and neural circuits that underpin behavioral anomalies that transcend psychiatric conditions. To study factors that contribute to individual differences in emotionality and stress reactivity, our laboratory utilized Sprague-Dawley rats that were selectively bred for differences in novelty exploration. Selective breeding for low versus high locomotor response to novelty produced rat lines that differ in behavioral domains relevant to anxiety and depression, particularly the RDoC Negative Valence domains, including acute threat, potential threat, and loss. Bred Low Novelty Responder (LR) rats, relative to their High Responder (HR) counterparts, display high levels of behavioral inhibition, conditioned and unconditioned fear, avoidance, passive stress coping, anhedonia, and psychomotor retardation. The HR/LR traits are heritable, emerge in the first weeks of life, and appear to be driven by alterations in the developing amygdala and hippocampus. Epigenomic and transcriptomic profiling in the developing and adult HR/LR brain suggest that DNA methylation and microRNAs, as well as differences in monoaminergic transmission (dopamine and serotonin in particular), contribute to their distinct behavioral phenotypes. This work exemplifies ways that animal models such as the HR/LR rats can be effectively used to study neural and molecular factors driving emotional behavior, which may pave the way toward improved understanding the neurobiological mechanisms involved in emotional disorders.