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ELife Jun 2023The ability to associate reward-predicting stimuli with adaptive behavior is frequently attributed to the prefrontal cortex, but the stimulus-specificity, spatial...
The ability to associate reward-predicting stimuli with adaptive behavior is frequently attributed to the prefrontal cortex, but the stimulus-specificity, spatial distribution, and stability of prefrontal cue-reward associations are unresolved. We trained head-fixed mice on an olfactory Pavlovian conditioning task and measured the coding properties of individual neurons across space (prefrontal, olfactory, and motor cortices) and time (multiple days). Neurons encoding cues or licks were most common in the olfactory and motor cortex, respectively. By quantifying the responses of cue-encoding neurons to six cues with varying probabilities of reward, we unexpectedly found value coding in all regions we sampled, with some enrichment in the prefrontal cortex. We further found that prefrontal cue and lick codes were preserved across days. Our results demonstrate that individual prefrontal neurons stably encode components of cue-reward learning within a larger spatial gradient of coding properties.
Topics: Animals; Mice; Cues; Learning; Adaptation, Psychological; Conditioning, Classical; Reward
PubMed: 37382590
DOI: 10.7554/eLife.84604 -
Cell Reports Aug 2023Long-term memory (LTM) requires learning-induced synthesis of new proteins allocated to specific neurons and synapses in a neural circuit. Not all learned information,...
Long-term memory (LTM) requires learning-induced synthesis of new proteins allocated to specific neurons and synapses in a neural circuit. Not all learned information, however, becomes permanent memory. How the brain gates relevant information into LTM remains unclear. In Drosophila adults, weak learning after a single training session in an olfactory aversive task typically does not induce protein-synthesis-dependent LTM. Instead, strong learning after multiple spaced training sessions is required. Here, we report that pre-synaptic active-zone protein synthesis and cholinergic signaling from the early α/β subset of mushroom body (MB) neurons produce a downstream inhibitory effect on LTM formation. When we eliminated inhibitory signaling from these neurons, weak learning was then sufficient to form LTM. This bidirectional circuit mechanism modulates the transition between distinct memory phase functions in different subpopulations of MB neurons in the olfactory memory circuit.
PubMed: 37590142
DOI: 10.1016/j.celrep.2023.112974 -
ELife Sep 2023We still face fundamental gaps in understanding how molecular plastic changes of synapses intersect with circuit operation to define behavioral states. Here, we show...
We still face fundamental gaps in understanding how molecular plastic changes of synapses intersect with circuit operation to define behavioral states. Here, we show that an antagonism between two conserved regulatory proteins, Spinophilin (Spn) and Syd-1, controls presynaptic long-term plasticity and the maintenance of olfactory memories in . While mutants could not trigger nanoscopic active zone remodeling under homeostatic challenge and failed to stably potentiate neurotransmitter release, concomitant reduction of Syd-1 rescued all these deficits. The Spn/Syd-1 antagonism converged on active zone close F-actin, and genetic or acute pharmacological depolymerization of F-actin rescued the deficits by allowing access to synaptic vesicle release sites. Within the intrinsic mushroom body neurons, the Spn/Syd-1 antagonism specifically controlled olfactory memory stabilization but not initial learning. Thus, this evolutionarily conserved protein complex controls behaviorally relevant presynaptic long-term plasticity, also observed in the mammalian brain but still enigmatic concerning its molecular mechanisms and behavioral relevance.
PubMed: 37767892
DOI: 10.7554/eLife.86084 -
Frontiers in Neural Circuits 2024In the mouse olfactory system, odor information is converted to a topographic map of activated glomeruli in the olfactory bulb (OB). Although the arrangement of... (Review)
Review
In the mouse olfactory system, odor information is converted to a topographic map of activated glomeruli in the olfactory bulb (OB). Although the arrangement of glomeruli is genetically determined, the glomerular structure is plastic and can be modified by environmental stimuli. If the pups are exposed to a particular odorant, responding glomeruli become larger recruiting the dendrites of connecting projection neurons and interneurons. This imprinting not only increases the sensitivity to the exposed odor, but also imposes the positive quality on imprinted memory. External odor information represented as an odor map in the OB is transmitted to the olfactory cortex (OC) and amygdala for decision making to elicit emotional and behavioral outputs using two distinct neural pathways, innate and learned. Innate olfactory circuits start to work right after birth, whereas learned circuits become functional later on. In this paper, the recent progress will be summarized in the study of olfactory circuit formation and odor perception in mice. We will also propose new hypotheses on the timing and gating of olfactory circuit activity in relation to the respiration cycle.
Topics: Animals; Mice; Sensation; Smell; Odorants; Amygdala; Perception
PubMed: 38434487
DOI: 10.3389/fncir.2024.1342576 -
Journal of the Royal Society, Interface Nov 2023Artificial intelligence (AI) and machine learning (ML) present revolutionary opportunities to enhance our understanding of animal behaviour and conservation strategies.... (Review)
Review
Artificial intelligence (AI) and machine learning (ML) present revolutionary opportunities to enhance our understanding of animal behaviour and conservation strategies. Using elephants, a crucial species in Africa and Asia's protected areas, as our focal point, we delve into the role of AI and ML in their conservation. Given the increasing amounts of data gathered from a variety of sensors like cameras, microphones, geophones, drones and satellites, the challenge lies in managing and interpreting this vast data. New AI and ML techniques offer solutions to streamline this process, helping us extract vital information that might otherwise be overlooked. This paper focuses on the different AI-driven monitoring methods and their potential for improving elephant conservation. Collaborative efforts between AI experts and ecological researchers are essential in leveraging these innovative technologies for enhanced wildlife conservation, setting a precedent for numerous other species.
Topics: Animals; Elephants; Artificial Intelligence; Conservation of Natural Resources; Animals, Wild
PubMed: 37963556
DOI: 10.1098/rsif.2023.0367 -
ELife Sep 2023Tastes typically evoke innate behavioral responses that can be broadly categorized as acceptance or rejection. However, research in indicates that taste responses also...
Tastes typically evoke innate behavioral responses that can be broadly categorized as acceptance or rejection. However, research in indicates that taste responses also exhibit plasticity through experience-dependent changes in mushroom body circuits. In this study, we develop a novel taste learning paradigm using closed-loop optogenetics. We find that appetitive and aversive taste memories can be formed by pairing gustatory stimuli with optogenetic activation of sensory neurons or dopaminergic neurons encoding reward or punishment. As with olfactory memories, distinct dopaminergic subpopulations drive the parallel formation of short- and long-term appetitive memories. Long-term memories are protein synthesis-dependent and have energetic requirements that are satisfied by a variety of caloric food sources or by direct stimulation of MB-MP1 dopaminergic neurons. Our paradigm affords new opportunities to probe plasticity mechanisms within the taste system and understand the extent to which taste responses depend on experience.
PubMed: 37750673
DOI: 10.7554/eLife.81535 -
Learning & Memory (Cold Spring Harbor,... Dec 2023Male and female 3xTg-AD mice between 5 and 24 mo of age and their B6129F2/J wild-type controls were tested on a series of 18 olfactory discrimination and reversal tasks...
Male and female 3xTg-AD mice between 5 and 24 mo of age and their B6129F2/J wild-type controls were tested on a series of 18 olfactory discrimination and reversal tasks in an operant olfactometer. All mice learned the odor discriminations and reversals to a criterion of 85% correct, but the 3xTg-AD mice made fewer errors than the B6129F2/J mice in the odor discriminations and in the first six reversal learning tasks. Many mice showed evidence of near errorless learning, and on the reversal tasks the 3xTg-AD mice showed more instances of near errorless learning than the B6129F2/J mice. There was no evidence of an age effect on odor discrimination, but there was a decrease in errorless reversal learning in aged B6129F2/J mice. In long-term memory tests, there was an increase in the number of errors made but no genotype difference. The high level of performance indicates that the mice were able to develop a "learning to learn" strategy. The finding that the 3xTg-AD mice outperformed their littermate controls provides an example of paradoxical functional facilitation in these mice.
Topics: Mice; Male; Female; Animals; Reversal Learning; Smell; Serial Learning
PubMed: 37977821
DOI: 10.1101/lm.053840.123 -
EClinicalMedicine Aug 2023Lack of specific definitions of clinical characteristics, disease severity, and risk and preventive factors of post-COVID-19 syndrome (PCS) severely impacts research and...
BACKGROUND
Lack of specific definitions of clinical characteristics, disease severity, and risk and preventive factors of post-COVID-19 syndrome (PCS) severely impacts research and discovery of new preventive and therapeutics drugs.
METHODS
This prospective multicenter cohort study was conducted from February 2020 to June 2022 in 5 countries, enrolling SARS-CoV-2 out- and in-patients followed at 3-, 6-, and 12-month from diagnosis, with assessment of clinical and biochemical features, antibody (Ab) response, Variant of Concern (VoC), and physical and mental quality of life (QoL). Outcome of interest was identification of risk and protective factors of PCS by clinical phenotype, setting, severity of disease, treatment, and vaccination status. We used SF-36 questionnaire to assess evolution in QoL index during follow-up and unsupervised machine learning algorithms (principal component analysis, PCA) to explore symptom clusters. Severity of PCS was defined by clinical phenotype and QoL. We also used generalized linear models to analyse the impact of PCS on QoL and associated risk and preventive factors. CT registration number: NCT05097677.
FINDINGS
Among 1796 patients enrolled, 1030 (57%) suffered from at least one symptom at 12-month. PCA identified 4 clinical phenotypes: chronic fatigue-like syndrome (CFs: fatigue, headache and memory loss, 757 patients, 42%), respiratory syndrome (REs: cough and dyspnoea, 502, 23%); chronic pain syndrome (CPs: arthralgia and myalgia, 399, 22%); and neurosensorial syndrome (NSs: alteration in taste and smell, 197, 11%). Determinants of clinical phenotypes were different (all comparisons p < 0.05): being female increased risk of CPs, NSs, and CFs; chronic pulmonary diseases of REs; neurological symptoms at SARS-CoV-2 diagnosis of REs, NSs, and CFs; oxygen therapy of CFs and REs; and gastrointestinal symptoms at SARS-CoV-2 diagnosis of CFs. Early treatment of SARS-CoV-2 infection with monoclonal Ab (all clinical phenotypes), corticosteroids therapy for mild/severe cases (NSs), and SARS-CoV-2 vaccination (CPs) were less likely to be associated to PCS (all comparisons p < 0.05). Highest reduction in QoL was detected in REs and CPs (43.57 and 43.86 vs 57.32 in PCS-negative controls, p < 0.001). Female sex (p < 0.001), gastrointestinal symptoms (p = 0.034) and renal complications (p = 0.002) during the acute infection were likely to increase risk of severe PCS (QoL <50). Vaccination and early treatment with monoclonal Ab reduced the risk of severe PCS (p = 0.01 and p = 0.03, respectively).
INTERPRETATION
Our study provides new evidence suggesting that PCS can be classified by clinical phenotypes with different impact on QoL, underlying possible different pathogenic mechanisms. We identified factors associated to each clinical phenotype and to severe PCS. These results might help in designing pathogenesis studies and in selecting high-risk patients for inclusion in therapeutic and management clinical trials.
FUNDING
The study received funding from the Horizon 2020 ORCHESTRA project, grant 101016167; from the Netherlands Organisation for Health Research and Development (ZonMw), grant 10430012010023; from Inserm, REACTing (REsearch & ACtion emergING infectious diseases) consortium and the French Ministry of Health, grant PHRC 20-0424.
PubMed: 37654668
DOI: 10.1016/j.eclinm.2023.102107 -
ArXiv Feb 2024Animals adjust their behavioral response to sensory input adaptively depending on past experiences. The flexible brain computation is crucial for survival and is of...
Animals adjust their behavioral response to sensory input adaptively depending on past experiences. The flexible brain computation is crucial for survival and is of great interest in neuroscience. The nematode C. elegans modulates its navigation behavior depending on the association of odor butanone with food (appetitive training) or starvation (aversive training), and will then climb up the butanone gradient or ignore it, respectively. However, the exact change in navigation strategy in response to learning is still unknown. Here we study the learned odor navigation in worms by combining precise experimental measurement and a novel descriptive model of navigation. Our model consists of two known navigation strategies in worms: biased random walk and weathervaning. We infer weights on these strategies by applying the model to worm navigation trajectories and the exact odor concentration it experiences. Compared to naive worms, appetitive trained worms up-regulate the biased random walk strategy, and aversive trained worms down-regulate the weathervaning strategy. The statistical model provides prediction with $>90 \%$ accuracy of the past training condition given navigation data, which outperforms the classical chemotaxis metric. We find that the behavioral variability is altered by learning, such that worms are less variable after training compared to naive ones. The model further predicts the learning-dependent response and variability under optogenetic perturbation of the olfactory neuron AWC$^\mathrm{ON}$. Lastly, we investigate neural circuits downstream from AWC$^\mathrm{ON}$ that are differentially recruited for learned odor-guided navigation. Together, we provide a new paradigm to quantify flexible navigation algorithms and pinpoint the underlying neural substrates.
PubMed: 38013890
DOI: No ID Found -
ACS Nano Nov 2023Deaf-blindness limits daily human activities, especially interactive modes of audio and visual perception. Although the developed standards have been verified as...
Deaf-blindness limits daily human activities, especially interactive modes of audio and visual perception. Although the developed standards have been verified as alternative communication methods, they are uncommon to the nondisabled due to the complicated learning process and inefficiency in terms of communicating distance and throughput. Therefore, the development of communication techniques employing innate sensory abilities including olfaction related to the cerebral limbic system processing emotions, memories, and recognition has been suggested for reducing the training level and increasing communication efficiency. Here, a skin-integrated and wireless olfactory interface system exploiting arrays of miniaturized odor generators (OGs) based on melting/solidifying odorous wax to release smell is introduced for establishing an advanced communication system between deaf-blind and non-deaf-blind. By optimizing the structure design of the OGs, each OG device is as small as 0.24 cm (length × width × height of 11 mm × 10 mm × 2.2 mm), enabling integration of up to 8 OGs on the epidermis between nose and lip for direct and rapid olfactory drive with a weight of only 24.56 g. By generating single or mixed odors, different linked messages could be delivered to a user within a short period in a wireless and programmable way. By adopting the olfactory interface message delivery system, the recognition rates for the messages have been improved 1.5 times that of the touch-based method, while the response times were immensely decreased 4 times. Thus, the presented wearable olfactory interface system exhibits great potential as an alternative message delivery method for the deaf-blind.
Topics: Humans; Odorants; Smell; Learning; Skin; Electronics
PubMed: 37917185
DOI: 10.1021/acsnano.3c08287