Transformation of acoustic information to sensory decision variables in the parietal cortex.

The process by which sensory evidence contributes to perceptual choices requires an understanding of its transformation into decision variables. Here, we address this issue by evaluating the neural representation of acoustic information in the auditory cortex-recipient parietal cortex, while gerbils either performed a two-alternative forced-choice auditory discrimination task or while they passively listened to identical acoustic stimuli. During task engagement, stimulus identity decoding performance from simultaneously recorded parietal neurons significantly correlated with psychometric sensitivity. In contrast, decoding performance during passive listening was significantly reduced. Principal component and geometric analyses revealed the emergence of low-dimensional encoding of linearly separable manifolds with respect to stimulus identity and decision, but only during task engagement. These findings confirm that the parietal cortex mediates a transition of acoustic representations into decision-related variables. Finally, using a clustering analysis, we identified three functionally distinct subpopulations of neurons that each encoded task-relevant information during separate temporal segments of a trial. Taken together, our findings demonstrate how parietal cortex neurons integrate and transform encoded auditory information to guide sound-driven perceptual decisions.

Recurrent Neural Circuits Overcome Partial Inactivation by Compensation and Re-learning.

Technical advances in artificial manipulation of neural activity have precipitated a surge in studying the causal contribution of brain circuits to cognition and behavior. However, complexities of neural circuits challenge interpretation of experimental results, necessitating new theoretical frameworks for reasoning about causal effects. Here, we take a step in this direction, through the lens of recurrent neural networks trained to perform perceptual decisions. We show that understanding the dynamical system structure that underlies network solutions provides a precise account for the magnitude of behavioral effects due to perturbations. Our framework explains past empirical observations by clarifying the most sensitive features of behavior, and how complex circuits compensate and adapt to perturbations. In the process, we also identify strategies that can improve the interpretability of inactivation experiments.

The Structure of Hippocampal CA1 Interactions Optimizes Spatial Coding across Experience.

Although much is known about how single neurons in the hippocampus represent an animal's position, how circuit interactions contribute to spatial coding is less well understood. Using a novel statistical estimator and theoretical modeling, both developed in the framework of maximum entropy models, we reveal highly structured CA1 cell-cell interactions in male rats during open field exploration. The statistics of these interactions depend on whether the animal is in a familiar or novel environment. In both conditions the circuit interactions optimize the encoding of spatial information, but for regimes that differ in the informativeness of their spatial inputs. This structure facilitates linear decodability, making the information easy to read out by downstream circuits. Overall, our findings suggest that the efficient coding hypothesis is not only applicable to individual neuron properties in the sensory periphery, but also to neural interactions in the central brain.SIGNIFICANCE STATEMENT Local circuit interactions play a key role in neural computation and are dynamically shaped by experience. However, measuring and assessing their effects during behavior remains a challenge. Here, we combine techniques from statistical physics and machine learning to develop new tools for determining the effects of local network interactions on neural population activity. This approach reveals highly structured local interactions between hippocampal neurons, which make the neural code more precise and easier to read out by downstream circuits, across different levels of experience. More generally, the novel combination of theory and data analysis in the framework of maximum entropy models enables traditional neural coding questions to be asked in naturalistic settings.

Desiderata for Normative Models of Synaptic Plasticity.

Normative models of synaptic plasticity use computational rationales to arrive at predictions of behavioral and network-level adaptive phenomena. In recent years, there has been an explosion of theoretical work in this realm, but experimental confirmation remains limited. In this review, we organize work on normative plasticity models in terms of a set of desiderata that, when satisfied, are designed to ensure that a given model demonstrates a clear link between plasticity and adaptive behavior, is consistent with known biological evidence about neural plasticity and yields specific testable predictions. As a prototype, we include a detailed analysis of the REINFORCE algorithm. We also discuss how new models have begun to improve on the identified criteria and suggest avenues for further development. Overall, we provide a conceptual guide to help develop neural learning theories that are precise, powerful, and experimentally testable.

Optimal recall from bounded metaplastic synapses: predicting functional adaptations in hippocampal area CA3.

A venerable history of classical work on autoassociative memory has significantly shaped our understanding of several features of the hippocampus, and most prominently of its CA3 area, in relation to memory storage and retrieval. However, existing theories of hippocampal memory processing ignore a key biological constraint affecting memory storage in neural circuits: the bounded dynamical range of synapses. Recent treatments based on the notion of metaplasticity provide a powerful model for individual bounded synapses; however, their implications for the ability of the hippocampus to retrieve memories well and the dynamics of neurons associated with that retrieval are both unknown. Here, we develop a theoretical framework for memory storage and recall with bounded synapses. We formulate the recall of a previously stored pattern from a noisy recall cue and limited-capacity (and therefore lossy) synapses as a probabilistic inference problem, and derive neural dynamics that implement approximate inference algorithms to solve this problem efficiently. In particular, for binary synapses with metaplastic states, we demonstrate for the first time that memories can be efficiently read out with biologically plausible network dynamics that are completely constrained by the synaptic plasticity rule, and the statistics of the stored patterns and of the recall cue. Our theory organises into a coherent framework a wide range of existing data about the regulation of excitability, feedback inhibition, and network oscillations in area CA3, and makes novel and directly testable predictions that can guide future experiments.

Curriculum learning inspired by behavioral shaping trains neural networks to adopt animal-like decision making strategies.

Recurrent neural networks (RNN) are ubiquitously used in neuroscience to capture both neural dynamics and behaviors of living systems. However, when it comes to complex cognitive tasks, traditional methods for training RNNs can fall short in capturing crucial aspects of animal behavior. To address this challenge, we take inspiration from a commonly used (though rarely appreciated) approach from the experimental neuroscientist's toolkit: behavioral shaping. Our solution leverages task compositionality and models the animal's relevant learning experiences prior to the task. Taking as target a temporal wagering task previously studied in rats, we designed a pretraining curriculum of simpler cognitive tasks that are prerequisites for performing it well. These pretraining tasks are not just simplified versions of the temporal wagering task, but reflect relevant sub-computations. We show that this approach is required for RNNs to adopt similar strategies as rats, including long-timescale inference of latent states, which conventional pretraining approaches fail to capture. Mechanistically, our pretraining supports the development of key dynamical systems features needed for implementing both inference and value-based decision making. Overall, our approach addresses a gap in neural network model training by incorporating inductive biases of animals, which is important when modeling complex behaviors that rely on computational abilities acquired from past experiences.

Context-invariant beliefs are supported by dynamic reconfiguration of single unit functional connectivity in prefrontal cortex of male macaques.

Natural behaviors occur in closed action-perception loops and are supported by dynamic and flexible beliefs abstracted away from our immediate sensory milieu. How this real-world flexibility is instantiated in neural circuits remains unknown. Here, we have male macaques navigate in a virtual environment by primarily leveraging sensory (optic flow) signals, or by more heavily relying on acquired internal models. We record single-unit spiking activity simultaneously from the dorsomedial superior temporal area (MSTd), parietal area 7a, and the dorso-lateral prefrontal cortex (dlPFC). Results show that while animals were able to maintain adaptive task-relevant beliefs regardless of sensory context, the fine-grain statistical dependencies between neurons, particularly in 7a and dlPFC, dynamically remapped with the changing computational demands. In dlPFC, but not 7a, destroying these statistical dependencies abolished the area's ability for cross-context decoding. Lastly, correlational analyses suggested that the more unit-to-unit couplings remapped in dlPFC, and the less they did so in MSTd, the less were population codes and behavior impacted by the loss of sensory evidence. We conclude that dynamic functional connectivity between neurons in prefrontal cortex maintain a stable population code and context-invariant beliefs during naturalistic behavior.

A common computational and neural anomaly across mouse models of autism.

Computational psychiatry has suggested that humans within the autism spectrum disorder (ASD) inflexibly update their expectations (i.e., Bayesian priors). Here, we leveraged high-yield rodent psychophysics (n = 75 mice), extensive behavioral modeling (including principled and heuristics), and (near) brain-wide single cell extracellular recordings (over 53k units in 150 brain areas) to ask (1) whether mice with different genetic perturbations associated with ASD show this same computational anomaly, and if so, (2) what neurophysiological features are shared across genotypes in subserving this deficit. We demonstrate that mice harboring mutations in Fmr1 , Cntnap2 , and Shank3B show a blunted update of priors during decision-making. Neurally, the differentiating factor between animals flexibly and inflexibly updating their priors was a shift in the weighting of prior encoding from sensory to frontal cortices. Further, in mouse models of ASD frontal areas showed a preponderance of units coding for deviations from the animals' long-run prior, and sensory responses did not differentiate between expected and unexpected observations. These findings demonstrate that distinct genetic instantiations of ASD may yield common neurophysiological and behavioral phenotypes.

Hippocampal neuronal activity is aligned with action plans.

Neurons in the hippocampus are correlated with different variables, including space, time, sensory cues, rewards, and actions, where the extent of tuning depends on ongoing task demands. However, it remains uncertain whether such diverse tuning corresponds to distinct functions within the hippocampal network or if a more generic computation can account for these observations. To disentangle the contribution of externally driven cues versus internal computation, we developed a task in mice where space, auditory tones, rewards, and context were juxtaposed with changing relevance. High-density electrophysiological recordings revealed that neurons were tuned to each of these modalities. By comparing movement paths and action sequences, we observed that external variables had limited direct influence on hippocampal firing. Instead, spiking was influenced by online action plans modulated by goal uncertainty. Our results suggest that internally generated cell assembly sequences are selected and updated by action plans toward deliberate goals. The apparent tuning of hippocampal neuronal spiking to different sensory modalities might emerge due to alignment to the afforded action progression within a task rather than representation of external cues.

Feedforward inhibition and synaptic scaling--two sides of the same coin?

Feedforward inhibition and synaptic scaling are important adaptive processes that control the total input a neuron can receive from its afferents. While often studied in isolation, the two have been reported to co-occur in various brain regions. The functional implications of their interactions remain unclear, however. Based on a probabilistic modeling approach, we show here that fast feedforward inhibition and synaptic scaling interact synergistically during unsupervised learning. In technical terms, we model the input to a neural circuit using a normalized mixture model with Poisson noise. We demonstrate analytically and numerically that, in the presence of lateral inhibition introducing competition between different neurons, Hebbian plasticity and synaptic scaling approximate the optimal maximum likelihood solutions for this model. Our results suggest that, beyond its conventional use as a mechanism to remove undesired pattern variations, input normalization can make typical neural interaction and learning rules optimal on the stimulus subspace defined through feedforward inhibition. Furthermore, learning within this subspace is more efficient in practice, as it helps avoid locally optimal solutions. Our results suggest a close connection between feedforward inhibition and synaptic scaling which may have important functional implications for general cortical processing.

Desiderata for normative models of synaptic plasticity.

Normative models of synaptic plasticity use a combination of mathematics and computational simulations to arrive at predictions of behavioral and network-level adaptive phenomena. In recent years, there has been an explosion of theoretical work on these models, but experimental confirmation is relatively limited. In this review, we organize work on normative plasticity models in terms of a set of desiderata which, when satisfied, are designed to guarantee that a model has a clear link between plasticity and adaptive behavior, consistency with known biological evidence about neural plasticity, and specific testable predictions. We then discuss how new models have begun to improve on these criteria and suggest avenues for further development. As prototypes, we provide detailed analyses of two specific models - REINFORCE and the Wake-Sleep algorithm. We provide a conceptual guide to help develop neural learning theories that are precise, powerful, and experimentally testable.

Context-invariant beliefs are supported by dynamic reconfiguration of single unit functional connectivity in prefrontal cortex.

Natural behaviors occur in closed action-perception loops and are supported by dynamic and flexible beliefs abstracted away from our immediate sensory milieu. How this real-world flexibility is instantiated in neural circuits remains unknown. Here we have macaques navigate in a virtual environment by primarily leveraging sensory (optic flow) signals, or by more heavily relying on acquired internal models. We record single-unit spiking activity simultaneously from the dorsomedial superior temporal area (MSTd), parietal area 7a, and the dorso-lateral prefrontal cortex (dlPFC). Results show that while animals were able to maintain adaptive task-relevant beliefs regardless of sensory context, the fine-grain statistical dependencies between neurons, particularly in 7a and dlPFC, dynamically remapped with the changing computational demands. In dlPFC, but not 7a, destroying these statistical dependencies abolished the area's ability for cross-context decoding. Lastly, correlation analyses suggested that the more unit-to-unit couplings remapped in dlPFC, and the less they did so in MSTd, the less were population codes and behavior impacted by the loss of sensory evidence. We conclude that dynamic functional connectivity between prefrontal cortex neurons maintains a stable population code and context-invariant beliefs during naturalistic behavior with closed action-perception loops.

Targeted V1 comodulation supports task-adaptive sensory decisions.

Sensory-guided behavior requires reliable encoding of stimulus information in neural populations, and flexible, task-specific readout. The former has been studied extensively, but the latter remains poorly understood. We introduce a theory for adaptive sensory processing based on functionally-targeted stochastic modulation. We show that responses of neurons in area V1 of monkeys performing a visual discrimination task exhibit low-dimensional, rapidly fluctuating gain modulation, which is stronger in task-informative neurons and can be used to decode from neural activity after few training trials, consistent with observed behavior. In a simulated hierarchical neural network model, such labels are learned quickly and can be used to adapt downstream readout, even after several intervening processing stages. Consistently, we find the modulatory signal estimated in V1 is also present in the activity of simultaneously recorded MT units, and is again strongest in task-informative neurons. These results support the idea that co-modulation facilitates task-adaptive hierarchical information routing.

Catalyzing next-generation Artificial Intelligence through NeuroAI.

Neuroscience has long been an essential driver of progress in artificial intelligence (AI). We propose that to accelerate progress in AI, we must invest in fundamental research in NeuroAI. A core component of this is the embodied Turing test, which challenges AI animal models to interact with the sensorimotor world at skill levels akin to their living counterparts. The embodied Turing test shifts the focus from those capabilities like game playing and language that are especially well-developed or uniquely human to those capabilities - inherited from over 500 million years of evolution - that are shared with all animals. Building models that can pass the embodied Turing test will provide a roadmap for the next generation of AI.

Coding of latent variables in sensory, parietal, and frontal cortices during closed-loop virtual navigation.

We do not understand how neural nodes operate and coordinate within the recurrent action-perception loops that characterize naturalistic self-environment interactions. Here, we record single-unit spiking activity and local field potentials (LFPs) simultaneously from the dorsomedial superior temporal area (MSTd), parietal area 7a, and dorsolateral prefrontal cortex (dlPFC) as monkeys navigate in virtual reality to 'catch fireflies'. This task requires animals to actively sample from a closed-loop virtual environment while concurrently computing continuous latent variables: (i) the distance and angle travelled (i.e., path integration) and (ii) the distance and angle to a memorized firefly location (i.e., a hidden spatial goal). We observed a patterned mixed selectivity, with the prefrontal cortex most prominently coding for latent variables, parietal cortex coding for sensorimotor variables, and MSTd most often coding for eye movements. However, even the traditionally considered sensory area (i.e., MSTd) tracked latent variables, demonstrating path integration and vector coding of hidden spatial goals. Further, global encoding profiles and unit-to-unit coupling (i.e., noise correlations) suggested a functional subnetwork composed by MSTd and dlPFC, and not between these and 7a, as anatomy would suggest. We show that the greater the unit-to-unit coupling between MSTd and dlPFC, the more the animals' gaze position was indicative of the ongoing location of the hidden spatial goal. We suggest this MSTd-dlPFC subnetwork reflects the monkeys' natural and adaptive task strategy wherein they continuously gaze toward the location of the (invisible) target. Together, these results highlight the distributed nature of neural coding during closed action-perception loops and suggest that fine-grain functional subnetworks may be dynamically established to subserve (embodied) task strategies.

Sensitive and robust chemical detection using an olfactory brain-computer interface.

When it comes to detecting volatile chemicals, biological olfactory systems far outperform all artificial chemical detection devices in their versatility, speed, and specificity. Consequently, the use of trained animals for chemical detection in security, defense, healthcare, agriculture, and other applications has grown astronomically. However, the use of animals in this capacity requires extensive training and behavior-based communication. Here we propose an alternative strategy, a bio-electronic nose, that capitalizes on the superior capability of the mammalian olfactory system, but bypasses behavioral output by reading olfactory information directly from the brain. We engineered a brain-computer interface that captures neuronal signals from an early stage of olfactory processing in awake mice combined with machine learning techniques to form a sensitive and selective chemical detector. We chronically implanted a grid electrode array on the surface of the mouse olfactory bulb and systematically recorded responses to a large battery of odorants and odorant mixtures across a wide range of concentrations. The bio-electronic nose has a comparable sensitivity to the trained animal and can detect odors on a variable background. We also introduce a novel genetic engineering approach that modifies the relative abundance of particular olfactory receptors in order to improve the sensitivity of our bio-electronic nose for specific chemical targets. Our recordings were stable over months, providing evidence for robust and stable decoding over time. The system also works in freely moving animals, allowing chemical detection to occur in real-world environments. Our bio-electronic nose outperforms current methods in terms of its stability, specificity, and versatility, setting a new standard for chemical detection.

Independent component analysis in spiking neurons.

Although models based on independent component analysis (ICA) have been successful in explaining various properties of sensory coding in the cortex, it remains unclear how networks of spiking neurons using realistic plasticity rules can realize such computation. Here, we propose a biologically plausible mechanism for ICA-like learning with spiking neurons. Our model combines spike-timing dependent plasticity and synaptic scaling with an intrinsic plasticity rule that regulates neuronal excitability to maximize information transmission. We show that a stochastically spiking neuron learns one independent component for inputs encoded either as rates or using spike-spike correlations. Furthermore, different independent components can be recovered, when the activity of different neurons is decorrelated by adaptive lateral inhibition.

Subpopulations of neurons in lOFC encode previous and current rewards at time of choice.

Studies of neural dynamics in lateral orbitofrontal cortex (lOFC) have shown that subsets of neurons that encode distinct aspects of behavior, such as value, may project to common downstream targets. However, it is unclear whether reward history, which may subserve lOFC's well-documented role in learning, is represented by functional subpopulations in lOFC. Previously, we analyzed neural recordings from rats performing a value-based decision-making task, and we documented trial-by-trial learning that required lOFC (Constantinople et al., 2019). Here, we characterize functional subpopulations of lOFC neurons during behavior, including their encoding of task variables. We found five distinct clusters of lOFC neurons, either based on clustering of their trial-averaged peristimulus time histograms (PSTHs), or a feature space defined by their average conditional firing rates aligned to different task variables. We observed weak encoding of reward attributes, but stronger encoding of reward history, the animal's left or right choice, and reward receipt across all clusters. Only one cluster, however, encoded the animal's reward history at the time shortly preceding the choice, suggesting a possible role in integrating previous and current trial outcomes at the time of choice. This cluster also exhibits qualitatively similar responses to identified corticostriatal projection neurons in a recent study (Hirokawa et al., 2019), and suggests a possible role for subpopulations of lOFC neurons in mediating trial-by-trial learning.

Integrated assessment of the food-water-land-ecosystems nexus in Europe: Implications for sustainability.

Climate and socio-economic change impacts are likely to cross traditional sectoral and regional boundaries with cascading indirect, and potentially far-reaching, repercussions. This is particularly important for the food-water-land-ecosystems (FWLE) nexus, which is fundamental for the achievement of at least six of the seventeen Sustainable Development Goals (SDGs). A holistic understanding of the FWLE nexus interactions and how and to what extent various exogenous drivers of change affect them is therefore central to cross-sectoral adaptation planning. Here, we present such an integrated assessment for Europe applying a regional Integrated Assessment Platform (IAP). The study explores a wide range of future climate and socio-economic scenarios using more than 900 model simulations. The results show that food production is likely to be the main driver of Europe's future landscape change dynamics (with or without climate change). Agriculture and land use allocation is often driven by complex cross-sectoral interactions with cascading effects on other sectors such as forestry, biodiversity, and water under the various scenarios. The modelling also highlighted that while sustaining current levels of food production at the European level could be achievable under most climate and socio-economic scenarios, there are significant regional differences with winners and losers. The analysis raises the question of whether current production and consumption policies are sustainable in the long-term. Such systematic integrated model-based analysis plays a crucial role in informing development of cross-sectoral policies that maximise synergies and minimise trade-offs across nexus sectors, regions, and scenarios. This is essential to achieve the SDGs.

How the Internally Organized Direction Sense Is Used to Navigate.

Head-direction cells preferentially discharge when the head points in a particular azimuthal direction, are hypothesized to collectively function as a single neural system for a unitary direction sense, and are believed to be essential for navigating extra-personal space by functioning like a compass. We tested these ideas by recording medial entorhinal cortex (MEC) head-direction cells while rats navigated on a familiar, continuously rotating disk that dissociates the environment into two spatial frames: one stationary and one rotating. Head-direction cells degraded directional tuning referenced to either of the externally referenced spatial frames, but firing rates, sub-second cell-pair action potential discharge relationships, and internally referenced directional tuning were preserved. MEC head-direction cell ensemble discharge collectively generates a subjective, internally referenced unitary representation of direction that, unlike a compass, is inconsistently registered to external landmarks during navigation. These findings indicate that MEC-based directional information is subjectively anchored, potentially providing for navigation without a stable externally anchored direction sense.