Abstract Animals must generalize from limited experience, yet behavioral experiments in the laboratory setting rarely assess whether or how rapidly they generalize. This contrasts with machine learning systems, where generalization is considered a fundamental test of learning, and emphasizes performance evaluation with new in-distribution or out-of- distribution examples. Here, we used an olfactory categorization task to investigate rules of generalization versus memorization in mice. We trained mice to discriminate between two target odorants mixed with a variable number (0-13) of background odors. There are 32766 possible mixture stimuli to be classified, yet mice learn to generalize from as few as 8 unique mixtures. This generalization is not due to limited memory capacity: mice successfully learned to group the same set of mixtures when category labels were randomly shuffled. Analysis of individual variability revealed features in learning dynamics during training that predict performance in the generalization phase. A linear supervised learning algorithm could describe the generalization from few exemplars well, whereas nonlinear classifiers were necessary to explain memorization. Our experiments suggest that mice have an inductive bias towards generalization, consistent with a preference for simple rules, and will memorize only when forced to do so.

In natural environments, animals must detect behaviorally relevant odors despite variability in both odor mixture composition and stimulus intensity. Although mice can identify salient odors embedded in complex mixtures, how target concentration and background complexity jointly constrain discrimination remains unclear. We trained mice in a two-alternative forced choice task to identify target odors embedded in mixtures containing up to 16 background components. After performance stabilized, we systematically varied target odor concentration. Discrimination accuracy declined with decreasing target concentration but showed little additional dependence on background complexity. Using a biophysically grounded model of olfactory bulb glomerular responses, we show that linear decoding reproduces behavioral performance when intrinsic neural noise dominates over background-driven variability. Manifold capacity analysis revealed that neural representations remain efficiently structured for odor discrimination despite variation in background complexity. These results define a noise-limited regime of olfactory discrimination in which target detectability is primarily constrained by neural sensitivity rather than background interference.

Odor cues in nature are sparse and fluctuating due to turbulent transport. To investigate how animals perceive these intermittent cues, we developed a behavioral task in which mice made binary decisions based on the total number of discrete odor pulses presented stochastically over several seconds. Mice quickly learned this task, placing higher perceptual weight to stimuli arriving during inhalation than exhalation, a phase dependency that strongly correlated with the magnitude of responses in olfactory sensory neurons. Neurons in the anterior piriform cortex responded to odor pulses with varying degrees of dependence on respiration phase. Single cortical neurons responded stochastically and transiently to odor pulses, leading to a representation that carries signatures of sensory evidence, but not its accumulation. Our study reveals that mice can integrate intermittent odor signals across dozens of breaths and that respiratory modulation imposes limits on sensory information acquisition that cortical circuits cannot overcome to improve behavior.

Accurate quantification of enteric methane emissions is essential for mitigating greenhouse gas outputs from livestock. However, existing methods such as respiration chambers and tracer gas systems remain costly, invasive, and impractical for large-scale deployment. Here, we present a modular electronic nose (e-nose) platform that introduces a materials-informed sensor-filter framework for selective methane detection in complex gas environments relevant to livestock monitoring. The system integrates three modules: an environmental unit for temperature, humidity, and carbon dioxide tracking; a volatile organic compound module; and a methane-selective unit comprising a metal oxide sensor with a dual-layer adsorbent filter made of activated carbon spheres and a polyethylene terephthalate (PET) membrane. This hybrid, dual-layer adsorptive filter enables a sensor-filter codesign strategy that suppresses both polar and non-polar interferents while preserving methane transport, shifting the dominant selectivity mechanism from surface oxygen competitive depletion to diffusion-mediated filtering. The methane-selective sensor exhibited a strong signal-to-noise ratio (33.9 dB), low detection limit (7.8 ppm), and excellent linearity (R2 = 0.999). In methane-pentane mixtures (20-1000 ppm), the filtered sensor maintained low error (similar to 13%), over 100-fold lower than unfiltered counterparts. Controlled interferent studies elucidated how filters influence selectivity, offering a framework for designing sensor-filter pairs tailored to complex gas environments. Integrated with environmental compensation, this materials-informed, ear-tag-shaped e-nose establishes a deployment-oriented framework for scalable, non-invasive methane monitoring in livestock-relevant environments.

Identifying what individual neurons encode in higher-order visual cortex is an open problem. Responses resist intuitive parameterization, and the deep-network embeddings used in their place are black boxes. Here, we introduce NEURRATOR, a framework that decodes spiking activity into free-form natural-language narration of the viewed scene at single-neuron resolution. A learned encoder maps spike trains from arbitrary subsets of simultaneously-recorded neurons into the patch-embedding space of a frozen CLIP, from which a multimodal language model and sparse autoencoder generates and validates a description with no language-side training. Applied to Neuropixel recordings of mouse visual cortex during natural-movie viewing, NEURRATOR narrates from thousands of neurons, singular cortical regions, local populations, or from a molecularly-defined cell-types. We use this property to (i) quantify how decoding fidelity scales with population size and cortical region, and (ii) "neurrate", in plain language, what individual neurons and genetically-tagged inhibitory cell-types contribute to visual representation. This recasts cell identity from a classification target into a functional probe of the visual system, providing a new unit of biological insights in neural systems.

The architecture of early olfactory processing is a striking example of convergent evolution. Typically, a panel of broadly tuned receptors is selectively expressed in sensory neurons (each neuron expressing only one receptor), and each glomerulus receives projections from just one neuron type. Taken together, these three motifs-broad receptors, selective expression, and glomerular convergence-constitute "canonical olfaction," since a number of model organisms including mice and flies exhibit these features. The emergence of this distinctive architecture across evolutionary lineages suggests that it may be optimized for information processing, an idea known as efficient coding. In this work, we show that by maximizing mutual information one layer at a time, efficient coding recovers several features of canonical olfactory processing under realistic biophysical assumptions. We also explore the settings in which noncanonical olfaction may be advantageous. Along the way, we make several predictions relating olfactory circuits to features of receptor families and the olfactory environment.

Natural olfactory systems possess remarkable sensitivity and precision beyond what is currently achievable by engineered gas sensors. Unlike their artificial counterparts, noses are capable of distinguishing scents associated with mixtures of volatile molecules in complex, typically fluctuating environments and can adapt to changes. This perspective examines the multifaceted biological principles that provide olfactory systems their discriminatory prowess, and how these ideas can be ported to the design of electronic noses for substantial improvements in performance across metrics such as sensitivity and ability to speciate chemical mixtures. The topics examined herein include the fluid dynamics of odorants in natural channels; specificity and kinetics of odorant interactions with olfactory receptors and mucus linings; complex signal processing that spatiotemporally encodes physicochemical properties of odorants; active sampling techniques, like biological sniffing and nose repositioning; biological priming; and molecular chaperoning. Each of these components of natural olfactory systems are systmatically investigated, as to how they have been or can be applied to electronic noses. While not all artificial sensors can employ these strategies simultaneously, integrating a subset of bioinspired principles can address issues like sensitivity, drift, and poor selectivity, offering advancements in many sectors such as environmental monitoring, industrial safety, and disease diagnostics.

Does learning of task-relevant representations stop when behavior stops changing? Motivated by recent work in machine learning and the intuitive observation that human experts continue to learn after mastery, we hypothesize that task-specific representation learning in cortex can continue, even when behavior saturates. In a novel reanalysis of recently published neural data, we find evidence for such learning in posterior piriform cortex of mice following continued training on a task, long after behavior saturates at near-ceiling performance ("overtraining"). We demonstrate that class representations in cortex continue to separate during overtraining, so that examples that were incorrectly classified at the beginning of overtraining can abruptly be correctly classified later on, despite no changes in behavior during that time. We hypothesize this hidden learning takes the form of approximate margin maximization; we validate this and other predictions in the neural data, as well as build and interpret a simple synthetic model that recapitulates these phenomena. We conclude by demonstrating how this model of late-time feature learning implies an explanation for the empirical puzzle of overtraining reversal in animal learning, where task-specific representations are more robust to particular task changes because the learned features can be reused.

The widespread adoption of deep learning to model neural activity often relies on "black-box" approaches that lack an interpretable connection between neural activity and network parameters. Here, we propose using algorithm unrolling, a method for interpretable deep learning, to design the architecture of sparse deconvolutional neural networks and obtain a direct interpretation of network weights in relation to stimulus-driven single-neuron activity through a generative model. We introduce our method, deconvolutional unrolled neural learning (DUNL), and demonstrate its versatility by applying it to deconvolve single-trial local signals across multiple brain areas and recording modalities. We uncover multiplexed salience and reward prediction error signals from midbrain dopamine neurons, perform simultaneous event detection and characterization in somatosensory thalamus recordings, and characterize the heterogeneity of neural responses in the piriform cortex and across striatum during unstructured, naturalistic experiments. Our work leverages advances in interpretable deep learning to provide a mechanistic understanding of neural activity.

Associative learning depends on contingency, the degree to which a stimulus predicts an outcome. Despite its importance, the neural mechanisms linking contingency to behavior remain elusive. In the present study, we examined the dopamine activity in the ventral striatum-a signal implicated in associative learning-in a Pavlovian contingency degradation task in mice. We show that both anticipatory licking and dopamine responses to a conditioned stimulus decreased when additional rewards were delivered uncued, but remained unchanged if additional rewards were cued. These results conflict with contingency-based accounts using a traditional definition of contingency or a new causal learning model (ANCCR), but can be explained by temporal difference (TD) learning models equipped with an appropriate intertrial interval state representation. Recurrent neural networks trained within a TD framework develop state representations akin to our best 'handcrafted' model. Our findings suggest that the TD error can be a measure that describes both contingency and dopaminergic activity.

Target odorant detection in mixtures has been shown to become more difficult as the number of background odorants increases and falls below chance level in mixtures with 16 components. Our aim was to investigate target odorant detection in mixtures among healthy people and compare it between dysosmic patients and age- and gender-matched controls. Participants underwent extensive olfactory testing and performed two target odorant detection tasks. Eugenol (‘clove’) and phenylethanol (PEA, ‘rose’) were target odorants for all participants, whereas a third target was randomised. For each target odorant in task one (task two), there were four steps. Mixtures contained two (three) odorants in the first step and up to seven (eight) odorants in the fourth step. In each step, participants were asked to choose the sample with the target odorant from the three (two) jars presented. The study included 90 healthy people and 40 patients. As expected, probability of successful target odorant detection decreased as the number of odorants in the mixture increased. However, even when there were seven (eight) odorants in the mixture, around 50% (50%) of healthy people detected Eugenol and around 30% (40%) detected PEA. Furthermore, both distributions of successful target odorant detection differed from the expected binominal distribution of chance ( p  < 0.001). Patients performed worse at detecting Eugenol or PEA at each step than controls. Furthermore, there were significant positive correlations between task scores and olfactory function. In conclusion, target odorant detection is influenced by the target odorant, number of background odorants, and individual olfactory function.

Many animal groups are organized hierarchically, which generates behavioral states that facilitate social interactions. Although generally stable, social status can change, underscoring the plasticity of underlying neural circuits. We examined competition among unfamiliar male mice and uncovered how the molecular and biophysical characteristics of a forebrain-thalamocortical circuit affect hierarchy. We identify the mediodorsal thalamus (MDT) as a hub receiving inputs from the orbitofrontal cortex and basal forebrain and projecting to the caudal anterior cingulate cortex (cACC) to regulate competitive performance. This circuit becomes potentiated or depressed in high- and low-rank males, respectively, in part through altered expression of the voltage-gated ion channel Trpm3 and synaptic plasticity. In high-rank mice, MDT projections drive inhibition of cACC pyramidal cells, promoting winning, in a pattern strikingly opposite to the dorsomedial prefrontal cortex, where winners display increased pyramidal cell activity. Our data suggest a model in which hierarchy modulation relies on coordinated remodeling of multiple forebrain-thalamocortical circuits.

Animals actively sense their environment to extract features of interest to guide behaviors. For mammals, odors are prominent environmental features which are sampled by active modulation of sniffing and orofacial orientation. We sought to understand the strategies that mice use to navigate surface-bound odor cues. We presented mice with dynamic, non-repeating odor trails using a paper treadmill, and observed their behaviors as they collected rewards offered randomly along the trail. By combining high-speed videography over long distances with quantitative behavioral analyses, we find that mice rapidly learn to track odor trails persistently and precisely. Mice with a single nostril blocked can track odor trails, but with a lateral bias and lower precision than control animals. Tracking is severely impaired in animals with both nostrils intact but with interhemispheric communication disrupted by anterior commissure transection. Respiration measurements revealed that a sniff close to the trail triggers a rapid turn towards the trail, a reaction that is lost in commissure-cut animals. Importantly, trail tracking is not simply reactive but involves adaptation to and retention of a short-term memory of the trail geometry and statistics. Our results, recapitulated by a Bayesian inference model, indicate that mice combine immediate sensory information with an internal model of the odor environment to follow odor trails efficiently.

Dogs and laboratory mice are commonly trained to perform complex tasks by guiding them through a curriculum of simpler tasks ('shaping'). What are the principles behind effective shaping strategies? Here, we propose a teacher-student framework for shaping behavior, where an autonomous teacher agent decides its student's task based on the student's transcript of successes and failures on previously assigned tasks. Using algorithms for Monte Carlo planning under uncertainty, we show that near-optimal shaping algorithms achieve a careful balance between reinforcement and extinction. Near-optimal algorithms track learning rate to adaptively alternate between simpler and harder tasks. Based on this intuition, we derive an adaptive shaping heuristic with minimal parameters, which we show is near-optimal on a sequence learning task and robustly trains deep reinforcement learning agents on navigation tasks that involve sparse, delayed rewards. Extensions to continuous curricula are explored. Our work provides a starting point towards a general computational framework for shaping behavior that applies to both animals and artificial agents.

Associative learning depends on contingency, the degree to which a stimulus predicts an outcome. Despite its importance, the neural mechanisms linking contingency to behavior remain elusive. Here we examined the dopamine activity in the ventral striatum - a signal implicated in associative learning - in a Pavlovian contingency degradation task in mice. We show that both anticipatory licking and dopamine responses to a conditioned stimulus decreased when additional rewards were delivered uncued, but remained unchanged if additional rewards were cued. These results conflict with contingency-based accounts using a traditional definition of contingency or a novel causal learning model (ANCCR), but can be explained by temporal difference (TD) learning models equipped with an appropriate inter-trial-interval (ITI) state representation. Recurrent neural networks trained within a TD framework develop state representations like our best 'handcrafted' model. Our findings suggest that the TD error can be a measure that describes both contingency and dopaminergic activity.

The integration of neural representations in the two hemispheres is an important problem in neuroscience. Recent experiments revealed that odor responses in cortical neurons driven by separate stimulation of the two nostrils are highly correlated. This bilateral alignment points to structured inter-hemispheric connections, but detailed mechanism remains unclear. Here, we hypothesized that continuous exposure to environmental odors shapes these projections and modeled it as online learning with local Hebbian rule. We found that Hebbian learning with sparse connections achieves bilateral alignment, exhibiting a linear trade-off between speed and accuracy. We identified an inverse scaling relationship between the number of cortical neurons and the inter-hemispheric projection density required for desired alignment accuracy, i.e., more cortical neurons allow sparser inter-hemispheric projections. We next compared the alignment performance of local Hebbian rule and the global stochastic-gradient-descent (SGD) learning for artificial neural networks. We found that although SGD leads to the same alignment accuracy with modestly sparser connectivity, the same inverse scaling relation holds. We showed that their similar performance originates from the fact that the update vectors of the two learning rules align significantly throughout the learning process. This insight may inspire efficient sparse local learning algorithms for more complex problems.

Does learning of task-relevant representations stop when behavior stops changing? Motivated by recent theoretical advances in machine learning and the intuitive observation that human experts continue to learn from practice even after mastery, we hypothesize that task-specific representation learning can continue, even when behavior plateaus. In a novel reanalysis of recently published neural data, we find evidence for such learning in posterior piriform cortex of mice following continued training on a task, long after behavior saturates at near-ceiling performance ("overtraining"). This learning is marked by an increase in decoding accuracy from piriform neural populations and improved performance on held-out generalization tests. We demonstrate that class representations in cortex continue to separate during overtraining, so that examples that were incorrectly classified at the beginning of overtraining can abruptly be correctly classified later on, despite no changes in behavior during that time. We hypothesize this hidden yet rich learning takes the form of approximate margin maximization; we validate this and other predictions in the neural data, as well as build and interpret a simple synthetic model that recapitulates these phenomena. We conclude by showing how this model of late-time feature learning implies an explanation for the empirical puzzle of overtraining reversal in animal learning, where task-specific representations are more robust to particular task changes because the learned features can be reused.

Each olfactory cortical hemisphere receives ipsilateral odor information directly from the olfactory bulb and contralateral information indirectly from the other cortical hemisphere. Since neural projections to the olfactory cortex (OC) are disordered and nontopographic, spatial information cannot be used to align projections from the two sides like in the visual cortex. Therefore, how bilateral information is integrated in individual cortical neurons is unknown. We have found, in mice, that the odor responses of individual neurons to selective stimulation of each of the two nostrils are significantly correlated, such that odor identity decoding optimized with information arriving from one nostril transfers very well to the other side. Nevertheless, these aligned responses are asymmetric enough to allow decoding of stimulus laterality. Computational analysis shows that such matched odor tuning is incompatible with purely random connections but is explained readily by Hebbian plasticity structuring bilateral connectivity. Our data reveal that despite the distributed and fragmented sensory representation in the OC, odor information across the two hemispheres is highly coordinated.

To restore proper blood flow in blocked coronary arteries via angioplasty procedure, accurate placement of devices such as catheters, balloons, and stents under live fluoroscopy or diagnostic angiography is crucial. Identified balloon markers help in enhancing stent visibility in X-ray sequences, while the catheter tip aids in precise navigation and coregistering vessel structures, reducing the need for contrast in angiography. However, accurate detection of these devices in interventional X-ray sequences faces significant challenges, particularly due to occlusions from contrasted vessels and other devices and distractions from surrounding, resulting in the failure to track such small objects. While most tracking methods rely on spatial correlation of past and current appearance, they often lack strong motion comprehension essential for navigating through these challenging conditions, and fail to effectively detect multiple instances in the scene. To overcome these limitations, we propose a self-supervised learning approach that enhances its spatio-temporal understanding by incorporating supplementary cues and learning across multiple representation spaces on a large dataset. Followed by that, we introduce a generic real-time tracking framework that effectively leverages the pretrained spatio-temporal network and also takes the historical appearance and trajectory data into account. This results in enhanced localization of multiple instances of device landmarks. Our method outperforms state-of-the-art methods in interventional X-ray device tracking, especially stability and robustness, achieving an 87% reduction in max error for balloon marker detection and a 61% reduction in max error for catheter tip detection.