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Murthy, V. N.

Publications and source records attributed to Murthy, V. N..

At least 19 recordsLinked to original sources

An inductive bias for generalization in mouse olfactory learning

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.

animal behavior and cognition↗

Sparse input representations explain odor discrimination in complex, concentration-varying mixtures

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.

neuroscience↗

Simultaneous detection and estimation in olfactory sensing

The mammalian olfactory system shows an exceptional ability for rapid and accurate decoding of both the identity and concentration of odorants. Previous works have used the theory of compressed sensing to elucidate the algorithmic basis for this capability: decoding odor information from the responses of a restricted repertoire of receptors is possible because only a few relevant odorants are present in any given sensory scene. However, existing circuit models for olfactory decoding still cannot contend with the complexity of naturalistic olfactory scenes; they are limited to detection of a handful of odorants. Here, we propose a model for olfactory compressed sensing inspired by simultaneous localization and mapping algorithms in navigation, in which the set of present odors and their concentrations are inferred separately. We implement this split inference in a biologically-plausible recurrent circuit by introducing separate dynamics matched to the distinct nature of presence and concentration, and drawing on the framework of Mirrored Langevin Dynamics. This model can accurately infer presence and concentration at scale. Moreover, its circuit structure can be mapped onto the primary cell types of the olfactory bulb, giving a possible normative account for functional differences between mitral and tufted cells. Our approach offers a general path towards circuit algorithms for probabilistic inference--in olfactory sensing and beyond--that both perform well in naturalistic environments and make experimentally-testable predictions for neural response dynamics.

neuroscience↗

Developmental Connectomics of the Mouse Cerebellum

To uncover the developmental processes that establish the precise patterns of synaptic connectivity in the CNS, we employed a connectomic approach in the mouse cerebellar cortex between birth and 2 weeks of age. There were dramatic quantitative and qualitative changes in the structure and connectivity of cerebellar cells. Parallel fiber synapses onto Purkinje cells increased [~]500-fold, with the most rapid growth taking place a week after birth. To support this profound synaptogenesis, Purkinje cells generated thousands of transient parallel fiber-oriented filopodia that received nascent synapses from parallel fibers. Importantly, we find that granule cells initiate synaptic output onto Purkinje cells only after receiving mossy fiber input, revealing a sequential, input-dependent logic for circuit assembly. In sharp contrast to the concurrent pruning of climbing fiber inputs, parallel fiber connectivity expanded and became highly individualized during development. Despite anatomical overlap, neighboring Purkinje cells share significantly fewer parallel fiber inputs than expected by chance. Moreover, parallel fibers themselves diverged spatially, further enforcing selective input allocation and resulting in highly specific parallel fiber cohorts for each Purkinje cell. Our findings uncover a mechanistic sequence in which early afferent activity and transient cellular structures guide the selective wiring and expansion of parallel fiber input to Purkinje cells, establishing developmental principles that ensure functional specificity in the mature brain.

neuroscience↗

Convergent motifs of early olfactory processing are recapitulated by layer-wise efficient coding

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.

neuroscience↗

Mice navigate scent trails using predictive policies

Many terrestrial animals accurately follow odor trails, but their navigation strategies remain unclear. We presented mice with dynamic, non-repeating odor trails using a paper treadmill, and found that they rapidly learned to track trails effectively. Odor detections by one or both nostrils during inhalation evoked rapid, stereotyped motor responses. Blocking one nostril led to biased tracking, while disconnecting interhemispheric neural communication disrupted tracking almost entirely. We found that trail tracking is more than a reflex, with mice adapting their movements according to a memory of recently encountered trail geometry. A Bayesian model captures these behaviors, suggesting mice combine bilateral olfactory input with short-term memory to guide navigation actively. Functional perturbations and neural recordings from behaving animals implicate an early olfactory cortical region in trail tracking. These results lay the groundwork to uncover the computational architecture of sensorimotor integration in naturalistic tasks.

neuroscience↗

Perception and neural representation of intermittent odor stimuli in mice

Odor cues in nature are sparse and highly fluctuating due to turbulent transport. To investigate how animals perceive these intermittent cues, we developed a behavioral task in which head-restrained mice made binary decisions based on the total number of discrete odor pulses presented stochastically over several seconds. Mice readily learned this task, and their performance was well-described by widely used decision models. Logistic regression of binary choices against the timing of odor pulses within the respiratory cycle revealed that mice placed 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. The population response of anterior piriform cortex (APCx) neurons to odor pulses was also modulated by respiration phase, although individual neurons displayed varying levels of phase-dependence. Single APCx 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, but respiratory modulation of sensory inputs imposes limits on information acquisition that cortical circuits cannot overcome to improve behavior.

neuroscience↗

The role of prospective contingency in the control of behavior and dopamine signals during associative learning

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.

neuroscience↗

Interpretable deep learning for deconvolutional analysis of neural signals

The widespread adoption of deep learning to build models that capture the dynamics of neural populations is typically based on "black-box" approaches that lack an interpretable link between neural activity and network parameters. Here, we propose to apply 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 characterize our method, referred to as deconvolutional unrolled neural learning (DUNL), and show its versatility by applying it to deconvolve single-trial local signals across multiple brain areas and recording modalities. To exemplify use cases of our decomposition method, we uncover multiplexed salience and reward prediction error signals from midbrain dopamine neurons in an unbiased manner, perform simultaneous event detection and characterization in somatosensory thalamus recordings, and characterize the heterogeneity of neural responses in the piriform cortex and in the striatum during unstructured, naturalistic experiments. Our work leverages the advances in interpretable deep learning to gain a mechanistic understanding of neural activity.

neuroscience↗

Adaptive algorithms for shaping behavior

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 machine learning framework for shaping animal behavior, where an autonomous teacher agent decides its students task based on the students transcript of successes and failures on previously assigned tasks. Using autonomous teachers that plan a curriculum in a common sequence learning task, we show that near-optimal shaping algorithms adaptively alternate between simpler and harder tasks to carefully balance reinforcement and extinction. Based on this intuition, we derive an adaptive shaping heuristic with minimal parameters, which we show is near-optimal on the 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 animal behavior.

animal behavior and cognition↗

Distinct information conveyed to the olfactory bulb by feedforward input from the nose and feedback from the cortex

Sensory systems are organized hierarchically, but feedback projections frequently disrupt this order. In the olfactory bulb (OB), cortical feedback projections numerically match sensory inputs. To unravel information carried by these two streams, we imaged the activity of olfactory sensory neurons (OSNs) and cortical axons in the mouse OB using calcium indicators, multiphoton microscopy, and diverse olfactory stimuli. Odorant mixtures of increasing complexity evoked progressively denser OSN activity, yet cortical feedback activity was of similar sparsity for all stimuli. Representations of complex mixtures were similar in OSNs but were decorrelated in cortical axons. While OSN responses to increasing odorant concentrations exhibited a sigmoidal relationship, cortical axonal responses were complex and non-monotonic, which could be explained by a model with activity-dependent feedback inhibition in the cortex. Our study indicates that early-stage olfactory circuits have access to both local feedforward signals and global, efficiently formatted information about odor scenes through cortical feedback.

neuroscience↗

Neural circuits for fast Poisson compressed sensing in the olfactory bulb

Within a single sniff, the mammalian olfactory system can decode the identity and concentration of odorants wafted on turbulent plumes of air. Yet, it must do so given access only to the noisy, dimensionally-reduced representation of the odor world provided by olfactory receptor neurons. As a result, the olfactory system must solve a compressed sensing problem, relying on the fact that only a handful of the millions of possible odorants are present in a given scene. Inspired by this principle, past works have proposed normative compressed sensing models for olfactory decoding. However, these models have not captured the unique anatomy and physiology of the olfactory bulb, nor have they shown that sensing can be achieved within the 100-millisecond timescale of a single sniff. Here, we propose a rate-based Poisson compressed sensing circuit model for the olfactory bulb. This model maps onto the neuron classes of the olfactory bulb, and recapitulates salient features of their connectivity and physiology. For circuit sizes comparable to the human olfactory bulb, we show that this model can accurately detect tens of odors within the timescale of a single sniff. We also show that this model can perform Bayesian posterior sampling for accurate uncertainty estimation. Fast inference is possible only if the geometry of the neural code is chosen to match receptor properties, yielding a distributed neural code that is not axis-aligned to individual odor identities. Our results illustrate how normative modeling can help us map function onto specific neural circuits to generate new hypotheses.

neuroscience↗

Learning-dependent evolution of odor mixture representations in piriform cortex

Rodents can learn from exposure to rewarding odors to make better and quicker decisions. The piriform cortex is thought to be important for learning complex odor associations, however it is not understood exactly how it learns to remember discriminations between many, sometimes overlapping, odor mixtures. We investigated how odor mixtures are represented in the posterior piriform cortex (pPC) of mice while they learn to discriminate a unique target odor mixture against hundreds of nontarget mixtures. We find that a significant proportion of pPC neurons discriminate between the target and all other nontarget odor mixtures. Neurons that prefer the target odor mixture tend to respond with brief increases in firing rate at odor onset compared to other neurons, which exhibit sustained and/or decreased firing. We allowed mice to continue training after they had reached high levels of performance and find that pPC neurons become more selective for target odor mixtures as well as for randomly chosen repeated nontarget odor mixtures that mice did not have to discriminate from other nontargets. These single unit changes during overtraining are accompanied by better categorization decoding at the population level, even though behavioral metrics of mice such as reward rate and latency to respond do not change. However, when difficult ambiguous trial types are introduced, the robustness of the target selectivity is correlated with better performance on the difficult trials. Taken together, these data reveal pPC as a dynamic and robust system that can optimize for both current and possible future task demands at once.

neuroscience↗

Population geometry enables fast sampling in spiking neural networks

For animals to navigate an uncertain world, their brains need to estimate uncertainty at the timescales of sensations and actions. Sampling-based algorithms afford a theoretically-grounded framework for probabilistic inference in neural circuits, but it remains unknown how one can implement fast sampling algorithms in biologically-plausible spiking networks. Here, we propose to leverage the population geometry, controlled by the neural code and the neural dynamics, to implement fast samplers in spiking neural networks. We first show that two classes of spiking samplers--efficient balanced spiking networks that simulate Langevin sampling, and networks with probabilistic spike rules that implement Metropolis-Hastings sampling--can be unified within a common framework. We then show that careful choice of population geometry, corresponding to the natural space of parameters, enables rapid inference of parameters drawn from strongly-correlated high-dimensional distributions in both networks. Our results suggest design prin-ciples for algorithms for sampling-based probabilistic inference in spiking neural networks, yielding potential inspiration for neuromorphic computing and testable predictions for neurobiology.

neuroscience↗

Distinct representation of cue-outcome association by D1 and D2 neurons in the olfactory striatum

Positive and negative associations acquired through olfactory experience are thought to be especially strong and long-lasting. The conserved direct olfactory sensory input to the ventral striatal olfactory tubercle (OT) and its convergence with dense dopaminergic input to the OT could underlie this privileged form of associative memory, but how this process occurs is not well understood. We imaged the activity of the two canonical types of striatal neurons, expressing D1 or D2 type dopamine receptors, in the OT at cellular resolution while mice learned odor-outcome associations ranging from aversive to rewarding. D1 and D2 neurons both responded to rewarding and aversive odors. D1 neurons in the OT robustly and bidirectionally represented odor valence, responding similarly to odors predicting similar outcomes regardless of odor identity. This valence representation persisted even in the absence of a licking response to the odors and in the absence of the outcomes, indicating a true transformation of odor sensory information by D1 OT neurons. In contrast, D2 neuronal representation of the odor-outcome associations was weaker, contingent on a licking response by the mouse, and D2 neurons were more selective for odor identity than valence. Stimulus valence coding in the OT was modality-sensitive, with separate sets of D1 neurons responding to odors and sounds predicting the same outcomes, suggesting that integration of multimodal valence information happens downstream of the OT. Our results point to distinct representation of identity and valence of odor stimuli by D1 and D2 neurons in the OT.

neuroscience↗

Cooperative escape in ants and robots

The solution of complex problems by the collective action of simple agents in both biologically evolved and synthetically engineered systems involves cooperative action. Understanding the resulting emergent solutions requires integrating across the organismal behaviors of many individuals. Here we investigate an ecologically relevant collective task in black carpenter ants Camponotus pennsylvanicus: escape from a soft, erodible confining corral. Individual ants show a transition from individual exploratory excavation at random locations to spatially localized collective exploitative excavation and escape from the corral. A minimal continuum theory that coarse-grains over individual actions and considers their integrated influence on the environment leads to the emergence of an effective phase space of behaviors in terms of excavation strength and cooperation intensity. To test the theory over the range of predicted behaviors, we used custom-built robots (RAnts) that respond to stimuli and show the emergence (and failure) of cooperative excavation and escape. Overall, our approach shows how the cooperative completion of tasks can arise from relatively simple rules that involve the interaction of simple agents with a dynamically changing environment that serves as an enabler and modulator of behavior.

animal behavior and cognition↗

Multi-animal pose estimation and tracking with DeepLabCut

Estimating the pose of multiple animals is a challenging computer vision problem: frequent interactions cause occlusions and complicate the association of detected keypoints to the correct individuals, as well as having extremely similar looking animals that interact more closely than in typical multi-human scenarios. To take up this challenge, we build on DeepLabCut, a popular open source pose estimation toolbox, and provide high-performance animal assembly and tracking--features required for robust multi-animal scenarios. Furthermore, we integrate the ability to predict an animals identity directly to assist tracking (in case of occlusions). We illustrate the power of this framework with four datasets varying in complexity, which we release to serve as a benchmark for future algorithm development.

animal behavior and cognition↗

Bilateral alignment of receptive fields in the olfactory cortex points to non-random connectivity

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 are disordered and non-topographic, 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 highly matched, such that odor identity decoding optimized with information arriving from one nostril transfers very well to the other side. Remarkably, these aligned responses are nevertheless 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 olfactory cortex, odor information across the two hemispheres is highly coordinated.

neuroscience↗