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Long-term exposure to nicotine alters brain circuits and induces profound changes in decision-making strategies, affecting behaviors both related and unrelated to drug seeking and consumption. Using an intracranial self-stimulation reward-based foraging task, we investigated in mice the impact of chronic nicotine on midbrain dopamine neuron activity and its consequence on the trade-off between exploitation and exploration. Model-based and archetypal analysis revealed substantial inter-individual variability in decision-making strategies, with mice passively exposed to nicotine shifting toward a more exploitative profile compared to non-exposed animals. We then mimicked the effect of chronic nicotine on the tonic activity of dopamine neurons using optogenetics, and found that photo-stimulated mice adopted a behavioral phenotype similar to that of mice exposed to chronic nicotine. Our results reveal a key role of tonic midbrain dopamine in the exploration/exploitation trade-off and highlight a potential mechanism by which nicotine affects the exploration/exploitation balance and decision-making. Chronic nicotine exposure impacts various components of decision-making processes, such as exploratory behaviors. Here, the authors identify the cellular mechanism and show that chronic nicotine exposure increases the tonic activity of VTA dopaminergic neurons and reduces exploration in mice.

Using optogenetic activation of adult-born neurons in the mouse olfactory bulb, the authors find that selective stimulation of new interneurons generated during adulthood, but not earlier, accelerates learning in a two-odor discrimination task and improves olfactory memory. Thousand of local interneurons reach the olfactory bulb of adult rodents every day, but the functional effect of this process remains elusive. By selectively expressing channelrhodopsin in postnatal-born mouse neurons, we found that their activation accelerated difficult odor discrimination learning and improved memory. This amelioration was seen when photoactivation occurred simultaneously with odor presentation, but not when odor delivery lagged by 500 ms. In addition, learning was facilitated when light flashes were delivered at 40 Hz, but not at 10 Hz. Both in vitro and in vivo electrophysiological recordings of mitral cells revealed that 40-Hz stimuli produced enhanced GABAergic inhibition compared with 10-Hz stimulation. Facilitation of learning occurred specifically when photoactivated neurons were generated during adulthood. Taken together, our results demonstrate an immediate causal relationship between the activity of adult-born neurons and the function of the olfactory bulb circuit.

Nicotine intake is likely to result from a balance between the rewarding and aversive properties of the drug, yet the individual differences in neural activity that control aversion to nicotine and their adaptation during the addiction process remain largely unknown. Using a two-bottle choice experiment, we observed considerable heterogeneity in nicotine-drinking profiles in isogenic adult male mice, with about half of the mice persisting in nicotine consumption even at high concentrations, whereas the other half stopped consuming. We found that nicotine intake was negatively correlated with nicotine-evoked currents in the interpeduncular nucleus (IPN), and that prolonged exposure to nicotine, by weakening this response, decreased aversion to the drug, and hence boosted consumption. Lastly, using knock-out mice and local gene re-expression, we identified β4-containing nicotinic acetylcholine receptors of IPN neurons as molecular and cellular correlates of nicotine aversion. Collectively, our results identify the IPN as a substrate for individual variabilities and adaptations in nicotine consumption.

Preclinical studies of psychiatric disorders use animal models to investigate the impact of environmental factors or genetic mutations on complex traits such as decision-making and social interactions. Here, we introduce a method for the real-time analysis of the behaviour of mice housed in groups of up to four over several days and in enriched environments. The method combines computer vision through a depth-sensing infrared camera, machine learning for animal and posture identification, and radio-frequency identification to monitor the quality of mouse tracking. It tracks multiple mice accurately, extracts a list of behavioural traits of both individuals and the groups of mice, and provides a phenotypic profile for each animal. We used the method to study the impact of Shank2 and Shank3 gene mutations—mutations that are associated with autism—on mouse behaviour. Characterization and integration of data from the behavioural profiles of Shank2 and Shank3 mutant female mice revealed their distinctive activity levels and involvement in complex social interactions. A method that combines a depth-sensing camera and machine learning can track the movements of up to four mice in real time and for several days, extracting both individual and group behavioural traits.

Background Traditionally, in biomedical animal research, laboratory rodents are individually examined in test apparatuses outside of their home cages at selected time points. However, the outcome of such tests can be influenced by various factors and valuable information may be missed when the animals are only monitored for short periods. These issues can be overcome by longitudinally monitoring mice and rats in their home cages. To shed light on the development of home cage monitoring (HCM) and the current state-of-the-art, a systematic review was carried out on 521 publications retrieved through PubMed and Web of Science. Results Both the absolute (~ × 26) and relative (~ × 7) number of HCM-related publications increased from 1974 to 2020. There was a clear bias towards males and individually housed animals, but during the past decade (2011–2020), an increasing number of studies used both sexes and group housing. In most studies, animals were kept for short (up to 4 weeks) time periods in the HCM systems; intermediate time periods (4–12 weeks) increased in frequency in the years between 2011 and 2020. Before the 2000s, HCM techniques were predominantly applied for less than 12 h, while 24-h measurements have been more frequent since the 2000s. The systematic review demonstrated that manual monitoring is decreasing in relation to automatic techniques but still relevant. Until (and including) the 1990s, most techniques were applied manually but have been progressively replaced by automation since the 2000s. Independent of the year of publication, the main behavioral parameters measured were locomotor activity, feeding, and social behaviors; the main physiological parameters were heart rate and electrocardiography. External appearance-related parameters were rarely examined in the home cages. Due to technological progress and application of artificial intelligence, more refined and detailed behavioral parameters have been investigated in the home cage more recently. Conclusions Over the period covered in this study, techniques for HCM of mice and rats have improved considerably. This development is ongoing and further progress as well as validation of HCM systems will extend the applications to allow for continuous, longitudinal, non-invasive monitoring of an increasing range of parameters in group-housed small rodents in their home cages.

Opioid use disorder (OUD) is a chronic relapsing condition caused by prolonged opioid exposure, which triggers adaptive changes in the brain. These changes make it challenging to control or abstain from consuming, and significantly increase the risk of relapse. While the physical symptoms of withdrawal typically resolve within a few days, extended abstinence is frequently accompanied by the progressive development of emotional disturbances. Additionally, abstinent individuals often report social disengagement, or even social isolation that worsen the condition and participates in the development of comorbidities. These disturbances are similarly observed in murine models of opioid abstinence. However, traditional methods for assessing social deficits in rodents often rely on simplistic paradigms with limited behavioral metrics. Here, we utilized a well-established model of morphine administration followed by protracted abstinence, combined with the Live Mouse Tracker (LMT) system. Using the real-time video-based automated LMT system, we conducted longitudinal recordings of social behaviors over a 4-week period of morphine abstinence, during repeated social interaction sessions. The use of this method, offering an unbiased and precise behavioral characterization of social investigation between freely-moving male mice, revealed that while motor and activity-related disruptions emerge and resolve quickly immediately following the onset of abstinence, social deficits progressively intensify over time, reaching their peak 3 weeks after the final morphine administration. Additionally, the LMT provided detailed insights into subtle behavioral changes throughout the course of abstinence and within individual but also that early deficits in explorations and social interactions might serve as predictor for the severity of the late social deficits. These results point out the need to improve and implement unbiased tracking methods for a deeper and refined understanding of rodent behaviors modeling psychiatric conditions.

The study of food aversion in humans by the induction of illness is ethically unthinkable, and it is difficult to propose a type of food that is disgusting for everybody. However, although cheese is considered edible by most people, it can also be perceived as particularly disgusting to some individuals. As such, the perception of cheese constitutes a good model to study the cerebral processes of food disgust and aversion. In this study, we show that a higher percentage of people are disgusted by cheese than by other types of food. Functional magnetic resonance imaging then reveals that the internal and external globus pallidus and the substantia nigra belonging to the basal ganglia are more activated in participants who dislike or diswant to eat cheese (Anti) than in other participants who like to eat cheese, as revealed following stimulation with cheese odors and pictures. We suggest that the aforementioned basal ganglia structures commonly involved in reward are also involved in the aversive motivated behaviors. Our results further show that the ventral pallidum, a core structure of the reward circuit, is deactivated in Anti subjects stimulated by cheese in the wanting task, highlighting the suppression of motivation-related activation in subjects disgusted by cheese.

Ultrasonic vocalisation is a broadly used proxy to evaluate social communication in mouse models of neuropsychiatric disorders. The efficacy and robustness of testing these models suffer from limited knowledge of the structure and functions of these vocalisations as well as of the way to analyse the data. We created mouseTube , an open database with a web interface, to facilitate sharing and comparison of ultrasonic vocalisations data and metadata attached to a recording file. Metadata describe 1) the acquisition procedure, e.g ., hardware, software, sampling frequency, bit depth; 2) the biological protocol used to elicit ultrasonic vocalisations; 3) the characteristics of the individual emitting ultrasonic vocalisations ( e.g. , strain, sex, age). To promote open science and enable reproducibility, data are made freely available. The website provides searching functions to facilitate the retrieval of recording files of interest. It is designed to enable comparisons of ultrasonic vocalisation emission between strains, protocols or laboratories, as well as to test different analysis algorithms and to search for protocols established to elicit mouse ultrasonic vocalisations. Over the long term, users will be able to download and compare different analysis results for each data file. Such application will boost the knowledge on mouse ultrasonic communication and stimulate sharing and comparison of automatic analysis methods to refine phenotyping techniques in mouse models of neuropsychiatric disorders.

Mouse models of autism can be used to study evolutionarily conserved mechanisms underlying behavioral abnormalities in social communication and repetitive behaviors. genes code for synaptic scaffolding proteins at excitatory synapses and mutations in all genes have been associated with autism. Here, we present three behavioral aspects of the mutant mice deleted for exon 16 in . First, we treated mutant mice with methylphenidate to rescue the hyperactivity. Our failure to do so suggests that the hyperactivity displayed by mutant mice is not related to the one displayed by the typical mouse models of hyperactivity, and might be more closely related to manic-like behaviors. Second, by testing the effect of group housing and social isolation on social interest, we highlighted that mutant mice lack the typical flexibility to modulate social interest, in comparison with wild-type littermates. Finally, we established a new protocol to test for social recognition in a social context. We used this protocol to show that mutant mice were able to discriminate familiar and unknown conspecifics in free interactions. Altogether, these studies shed some light on specific aspects of the behavioral defects displayed by the mouse model. Such information could be used to orient therapeutic strategies and to design more specific tests to characterize the complex behavior of mouse models of autism.

Individuality is a striking feature of animal behavior. Individual animals differ in traits and preferences which shape their interactions and their prospects for survival. However, the mechanisms underlying behavioral individuation are poorly understood and are generally considered to be genetic-based. Here, we devised a large environment, Souris City, in which mice live continuously in large groups. We observed the emergence of individual differences in social behavior, activity levels, and cognitive traits, even though the animals had low genetic diversity (inbred C57BL/6J strain). We further show that the phenotypic divergence in individual behaviors was mirrored by developing differences in midbrain dopamine neuron firing properties. Strikingly, modifying the social environment resulted in a fast re-adaptation of both the animal’s traits and its dopamine firing pattern. Individuality can rapidly change upon social challenges, and does not just depend on the genetic status or the accumulation of small differences throughout development. Individual animals differ in behavioral traits, but the mechanisms underlying individuation are unclear. Here, the authors show that mice living in a ‘city’ develop individual behavior differences, associated with changes in dopamine cell firing, that can be reversed on moving them to a different social environment.