Biology subjects

Richards, B. A.

Publications and source records attributed to Richards, B. A..

15 recordsLinked to original sources

bioRxiv2026

Increased activity without changes in coupling between somata and apical dendrites during visual mismatches

Leading theories of cortical function posit that sensory processing involves a comparison between top-down predictions and bottom-up sensory data. Tests of these theories have been hampered by experimental challenges related to simultaneously recording top-down and bottom-up signals in response to sensory stimuli that either do or do not match internally-generated predictions. Here, we conduct dual-plane 2-photon calcium imaging near-simultaneously from distal apical dendrites and somata of pyramidal neurons in each of 4 different regions of mouse visual cortex while the mice are presented with visual sequences that can either match or mismatch previously habituated visual stimuli. Specifically, we examine the responses in the distal apical dendrites and cell bodies of pyramidal neurons while mice view either movie clips that reverse unexpectedly or Gabor patch sequences that have orientations that do not match habituated patterns. We find that in response to unexpected reversals in natural movies, both the apical dendrites and somata show increased activity that decreases over repeated exposures, consistent with a prediction error response. However, we do not find any clear evidence for increased activity in response to mismatches in Gabor sequences, beyond possible release from adaptation effects. We additionally use volumetric images to connect dendritic and somatic compartments and examine the coupling between connected dendrites and cell bodies in layer 5 pyramidal neurons. We do not find evidence for changes in coupling in response to mismatch stimuli, either for natural movies or Gabor sequences. Our results are consistent across four regions of visual cortex. We also observe that increased responses to reversals in natural movies are stronger in layer 2/3 than layer 5 pyramidal neurons. Altogether, these data suggest that visual cortex is sensitive to deviations from previously-experienced naturalistic inputs. Our data do not suggest that this mismatch sensitivity extends to artificial stimuli, nor do they support theories of prediction error causing changes in the coupling between apical dendrites and somata.

neuroscience↗

bioRxiv2024

Top-down feedback matters: Functional impact of brainlike connectivity motifs on audiovisual integration

Artificial neural networks (ANNs) are an important tool for studying neural computation, but many features of the brain are not captured by standard ANN architectures. One notable missing feature in most ANN models is top-down feedback, i.e. projections from higher-order layers to lower-order layers in the network. Top-down feedback is ubiquitous in the brain, and it has a unique modulatory impact on activity in neocortical pyramidal neurons. However, we still do not understand its computational role. Here we develop a deep neural network model that captures the core functional properties of top-down feedback in the neocortex, allowing us to construct hierarchical recurrent ANN models that more closely reflect the architecture of the brain. We use this to explore the impact of different hierarchical recurrent architectures on an audiovisual integration task. We find that certain hierarchies, namely those that mimic the architecture of the human brain, impart ANN models with a light visual bias similar to that seen in humans. This bias does not impair performance on the audiovisual tasks. The results further suggest that different configurations of top-down feedback make otherwise identically connected models functionally distinct from each other, and from traditional feedforward and laterally recurrent models. Altogether our findings demonstrate that modulatory top-down feedback is a computationally relevant feature of biological brains, and that incorporating it into ANNs affects their behavior and constrains the solutions its likely to discover.

neuroscience↗

bioRxiv2024

Sequential predictive learning is a unifying theory for hippocampal representation and replay

The mammalian hippocampus contains a cognitive map that represents an animals position in the environment 1 and generates offline "replay" 2,3 for the purposes of recall 4, planning 5,6, and forming long term memories 7. Recently, its been found that artificial neural networks trained to predict sensory inputs develop spatially tuned cells 8, aligning with predictive theories of hippocampal function 9-11. However, whether predictive learning can also account for the ability to produce offline replay is unknown. Here, we find that spatially-tuned cells, which robustly emerge from all forms of predictive learning, do not guarantee the presence of a cognitive map with the ability to generate replay. Offline simulations only emerged in networks that used recurrent connections and head-direction information to predict multi-step observation sequences, which promoted the formation of a continuous attractor reflecting the geometry of the environment. These offline trajectories were able to show wake-like statistics, autonomously replay recently experienced locations, and could be directed by a virtual head direction signal. Further, we found that networks trained to make cyclical predictions of future observation sequences were able to rapidly learn a cognitive map and produced sweeping representations of future positions reminiscent of hippocampal theta sweeps 12. These results demonstrate how hippocampal-like representation and replay can emerge in neural networks engaged in predictive learning, and suggest that hippocampal theta sequences reflect a circuit that implements a data-efficient algorithm for sequential predictive learning. Together, this framework provides a unifying theory for hippocampal functions and hippocampal-inspired approaches to artificial intelligence.

neuroscience↗

bioRxiv2022

Stimulus information guides the emergence of behavior related signals in primary somatosensory cortex during learning

Cortical neurons in primary sensory cortex carry not only sensory but also behavior-related information. However, it remains unclear how these types of information emerge and are integrated with one another over learning and what the relative contribution of activity in individual cells versus neuronal populations is in this process. Current evidence supports two opposing views of learning-related changes: 1) sensory information increases in primary cortex or 2) sensory information remains stable in primary cortex but its readout efficiency in association cortices increases. Here, we investigate these questions in primary sensory cortex during learning of a sensory task. Over the course of weeks, we imaged neuronal activity at different depths within layers 2 and 3 of the mouse vibrissal primary somatosensory cortex (vS1) before, during, and after training on a whisker-based object-localization task. We leveraged information theoretical analysis to quantify stimulus and behavior-related information in vS1 and estimate how much neural activity encoding sensory information is used to inform perceptual choices as sensory learning progresses. We also quantified the extent to which these types of information are supported by an individual neuron or population code. We found that, while sensory information rises progressively from the start of training, choice information is only present in the final stages of learning and is increasingly supported by a population code. Moreover, we demonstrate that not only the increase in available information, but also a more efficient readout of such information in primary sensory cortex mediate sensory learning. Together, our results highlight the importance of primary cortical neurons in perceptual learning.

neuroscience↗

bioRxiv2021

Forgetting Enhances Episodic Control with Structured Memories

Forgetting is a normal process in healthy brains, and evidence suggests that the mammalian brain forgets more than is required based on limitations of mnemonic capacity. Episodic memories, in particular, are liable to be forgotten over time. Researchers have hypothesized that it may be beneficial for decision making to forget episodic memories over time. Reinforcement learning offers a normative framework in which to test such hypotheses. Here, we show that a reinforcement learning agent that uses an episodic memory cache to find rewards in maze environments can forget a large percentage of older memories without any performance impairments, if they utilize mnemonic representations that contain structural information about space. Moreover, we show that some forgetting can actually provide a benefit in performance compared to agents with unbounded memories. Our analyses of the agents show that forgetting reduces the influence of outdated information and states which are not frequently visited on the policies produced by the episodic control system. These results support the hypothesis that some degree of forgetting can be beneficial for decision making, which can help to explain why the brain forgets more than is required by capacity limitations.

animal behavior and cognition↗

bioRxiv2021

Time cell encoding in deep reinforcement learning agents depends on mnemonic demands

The representation of "what happened when" is central to encoding episodic and working memories. Recently discovered hippocampal time cells are theorized to provide the neural substrate for such representations by forming distinct sequences that both encode time elapsed and sensory content. However, little work has directly addressed to what extent cognitive demands and temporal structure of experimental tasks affect the emergence and informativeness of these temporal representations. Here, we trained deep reinforcement learning (DRL) agents on a simulated trial-unique nonmatch-to-location (TUNL) task, and analyzed the activities of artificial recurrent units using neuroscience-based methods. We show that, after training, representations resembling both time cells and ramping cells (whose activity increases or decreases monotonically over time) simultaneously emerged in the same population of recurrent units. Furthermore, with simulated variations of the TUNL task that controlled for (1) memory demands during the delay period and (2) the temporal structure of the episodes, we show that memory demands are necessary for the time cells to encode information about the sensory stimuli, while the temporal structure of the task only affected the encoding of "what" and "when" by time cells minimally. Our findings help to reconcile current discrepancies regarding the involvement of time cells in memory-encoding by providing a normative framework. Our modelling results also provide concrete experimental predictions for future studies.

neuroscience↗

bioRxiv2021

Your head is there to move you around: Goal-driven models of the primate dorsal pathway

Neurons in the dorsal visual pathway of the mammalian brain are selective for motion stimuli, with the complexity of stimulus representations increasing along the hierarchy. This progression is similar to that of the ventral visual pathway, which is well characterized by artificial neural networks (ANNs) optimized for object recognition. In contrast, there are no image-computable models of the dorsal stream with comparable explanatory power. We hypothesized that the properties of dorsal stream neurons could be explained by a simple learning objective: the need for an organism to orient itself during self-motion. To test this hypothesis, we trained a 3D ResNet to predict an agents self-motion parameters from visual stimuli in a simulated environment. We found that the responses in this network accounted well for the selectivity of neurons in a large database of single-neuron recordings from the dorsal visual stream of non-human primates. In contrast, ANNs trained on an action recognition dataset through supervised or self-supervised learning could not explain responses in the dorsal stream, despite also being trained on naturalistic videos with moving objects. These results demonstrate that an ecologically relevant cost function can account for dorsal stream properties in the primate brain.

neuroscience↗

bioRxiv2021

Parallel and recurrent cascade models as a unifying force for understanding sub-cellular computation

Neurons are very complicated computational devices, incorporating numerous non-linear processes, particularly in their dendrites. Biophysical models capture these processes directly by explicitly modelling physiological variables, such as ion channels, current flow, membrane capacitance, etc. However, another option for capturing the complexities of real neural computation is to use cascade models, which treat individual neurons as a cascade of linear and non-linear operations, akin to a multi-layer artificial neural network. Recent research has shown that cascade models can capture single-cell computation well, but there are still a number of sub-cellular, regenerative dendritic phenomena that they cannot capture, such as the interaction between sodium, calcium, and NMDA spikes in different compartments. Here, we propose that it is possible to capture these additional phenomena using parallel, recurrent cascade models, wherein an individual neuron is modelled as a cascade of parallel linear and non-linear operations that can be connected recurrently, akin to a multi-layer, recurrent, artificial neural network. Given their tractable mathematical structure, we show that neuron models expressed in terms of parallel recurrent cascades can themselves be integrated into multi-layered artificial neural networks and trained to perform complex tasks. We go on to discuss potential implications and uses of these models for artificial intelligence. Overall, we argue that parallel, recurrent cascade models provide an important, unifying tool for capturing single-cell computation and exploring the algorithmic implications of physiological phenomena.

neuroscience↗

bioRxiv2021

Parallel inference of hierarchical latent dynamics in two-photon calcium imaging of neuronal populations

Dynamic latent variable modelling has provided a powerful tool for understanding how populations of neurons compute. For spiking data, such latent variable modelling can treat the data as a set of point-processes, due to the fact that spiking dynamics occur on a much faster timescale than the computational dynamics being inferred. In contrast, for other experimental techniques, the slow dynamics governing the observed data are similar in timescale to the computational dynamics that researchers want to infer. An example of this is in calcium imaging data, where calcium dynamics can have timescales on the order of hundreds of milliseconds. As such, the successful application of dynamic latent variable modelling to modalities like calcium imaging data will rest on the ability to disentangle the deeper- and shallower-level dynamical systems contributions to the data. To-date, no techniques have been developed to directly achieve this. Here we solve this problem by extending recent advances using sequential variational autoencoders for dynamic latent variable modelling of neural data. Our system VaLPACa (Variational Ladders for Parallel Autoencoding of Calcium imaging data) solves the problem of disentangling deeper- and shallower-level dynamics by incorporating a ladder architecture that can infer a hierarchy of dynamical systems. Using some built-in inductive biases for calcium dynamics, we show that we can disentangle calcium flux from the underlying dynamics of neural computation. First, we demonstrate with synthetic calcium data that we can correctly disentangle an underlying Lorenz attractor from calcium dynamics. Next, we show that we can infer appropriate rotational dynamics in spiking data from macaque motor cortex after it has been converted into calcium fluorescence data via a calcium dynamics model. Finally, we show that our method applied to real calcium imaging data from primary visual cortex in mice allows us to infer latent factors that carry salient sensory information about unexpected stimuli. These results demonstrate that variational ladder autoencoders are a promising approach for inferring hierarchical dynamics in experimental settings where the measured variable has its own slow dynamics, such as calcium imaging data. Our new, open-source tool thereby provides the neuroscience community with the ability to apply dynamic latent variable modelling to a wider array of data modalities.

neuroscience↗

bioRxiv2021

Learning from unexpected events in the neocortical microcircuit

Scientists have long conjectured that the neocortex learns the structure of the environment in a predictive, hierarchical manner. According to this conjecture, expected, predictable features are differentiated from unexpected ones by comparing bottom-up and top-down streams of information. It is theorized that the neocortex then changes the representation of incoming stimuli, guided by differences in the responses to expected and unexpected events. In line with this conjecture, different responses to expected and unexpected sensory features have been observed in spiking and somatic calcium events. However, it remains unknown whether these unexpected event signals occur in the distal apical dendrites where many top-down signals are received, and whether these signals govern subsequent changes in the brains stimulus representations. Here, we show that both somata and distal apical dendrites of cortical pyramidal neurons exhibit distinct unexpected event signals that systematically change over days. These findings were obtained by tracking the responses of individual somata and dendritic branches of layer 2/3 and layer 5 pyramidal neurons over multiple days in primary visual cortex of awake, behaving mice using two-photon calcium imaging. Many neurons in both layers 2/3 and 5 showed large differences between their responses to expected and unexpected events. Interestingly, these responses evolved in opposite directions in the somata and distal apical dendrites. These differences between the somata and distal apical dendrites may be important for hierarchical computation, given that these two compartments tend to receive bottom-up and top-down information, respectively.

neuroscience↗

bioRxiv2020

Learning function from structure in neuromorphic networks

The connection patterns of neural circuits in the brain form a complex network. Collective signaling within the network manifests as patterned neural activity, and is thought to support human cognition and adaptive behavior. Recent technological advances permit macro-scale reconstructions of biological brain networks. These maps, termed connectomes, display multiple non-random architectural features, including heavy-tailed degree distributions, segregated communities and a densely interconnected core. Yet, how computation and functional specialization emerge from network architecture remains unknown. Here we reconstruct human brain connectomes using in vivo diffusion-weighted imaging, and use reservoir computing to implement these connectomes as artificial neural networks. We then train these neuromorphic networks to learn a cognitive task. We show that biologically realistic neural architectures perform optimally when they display critical dynamics. We find that performance is driven by network topology, and that the modular organization of large-scale functional systems is computationally relevant. Throughout, we observe a prominent interaction between network structure and dynamics, such that the same underlying architecture can support a wide range of learning capacities across dynamical regimes. This work opens new opportunities to discover how the network organization of the brain optimizes cognitive capacity, conceptually bridging neuroscience and artificial intelligence.

neuroscience↗

bioRxiv2020

Learning to live with Dale's principle: ANNs with separate excitatory and inhibitory units

AO_SCPLOWBSTRACTC_SCPLOWThe units in artificial neural networks (ANNs) can be thought of as abstractions of biological neurons, and ANNs are increasingly used in neuroscience research. However, there are many important differences between ANN units and real neurons. One of the most notable is the absence of Dales principle, which ensures that biological neurons are either exclusively excitatory or inhibitory. Dales principle is typically left out of ANNs because its inclusion impairs learning. This is problematic, because one of the great advantages of ANNs for neuroscience research is their ability to learn complicated, realistic tasks. Here, by taking inspiration from feedforward inhibitory interneurons in the brain we show that we can develop ANNs with separate populations of excitatory and inhibitory units that learn just as well as standard ANNs. We call these networks Dales ANNs (DANNs). We present two insights that enable DANNs to learn well: (1) DANNs are related to normalization schemes, and can be initialized such that the inhibition centres and standardizes the excitatory activity, (2) updates to inhibitory neuron parameters should be scaled using corrections based on the Fisher Information matrix. These results demonstrate how ANNs that respect Dales principle can be built without sacrificing learning performance, which is important for future work using ANNs as models of the brain. The results may also have interesting implications for how inhibitory plasticity in the real brain operates.

neuroscience↗

bioRxiv2019

Deep learning for brains?: Different linear and nonlinear scaling in UK Biobank brain images vs. machine-learning datasets

In recent years, deep learning has unlocked unprecedented success in various domains, especially in image, text, and speech processing. These breakthroughs may hold promise for neuroscience and especially for brain-imaging investigators who start to analyze thousands of participants. However, deep learning is only beneficial if the data have nonlinear relationships and if they are exploitable at currently available sample sizes. We systematically profiled the performance of deep models, kernel models, and linear models as a function of sample size on UK Biobank brain images against established machine learning references. On MNIST and Zalando Fashion, prediction accuracy consistently improved when escalating from linear models to shallow-nonlinear models, and further improved when switching to deep-nonlinear models. The more observations were available for model training, the greater the performance gain we saw. In contrast, using structural or functional brain scans, simple linear models performed on par with more complex, highly parameterized models in age/sex prediction across increasing sample sizes. In fact, linear models kept improving as the sample size approached [~]10,000 participants. Our results indicate that the increase in performance of linear models with additional data does not saturate at the limit of current feasibility. Yet, nonlinearities of common brain scans remain largely inaccessible to both kernel and deep learning methods at any examined scale.

bioinformatics↗

bioRxiv2019

Distinct roles of parvalbumin and somatostatin interneurons in the synchronization of spike-times in the neocortex

Synchronization of precise spike-times across multiple neurons carries information about sensory stimuli. Inhibitory interneurons are suggested to promote this synchronization, but it is unclear whether distinct interneuron subtypes provide different contributions. To test this, we examined single-unit recordings from barrel cortex in vivo and used optogenetics to determine the contribution of two classes of inhibitory interneurons: parvalbumin (PV)- and somatostatin (SST)-positive interneurons to spike-timing synchronization across cortical layers. We found that PV interneurons preferentially promote the synchronization of spike-times when instantaneous firing-rates are low (<12 Hz), whereas SST interneurons preferentially promote the synchronization of spike-times when instantaneous firing-rates are high (>12 Hz). Furthermore, using a computational model, we demonstrate that these effects can be explained by PV and SST interneurons having preferential contribution to feedforward and feedback inhibition, respectively. Our findings demonstrate that distinct subtypes of inhibitory interneurons have frequency-selective roles in spatio-temporal synchronization of precise spike-times.

neuroscience↗

bioRxiv2019

Neocortical inhibitory interneuron subtypes display distinct responses to synchrony and rate of inputs

Populations of neurons in the neocortex can carry information with both the synchrony and the rate of their spikes. However, it is unknown whether distinct subtypes of neurons in the cortical microcircuit are more sensitive to information carried by synchrony versus rate. Here, we address this question using patterned optical stimulation in slices of barrel cortex from transgenic mouse lines labelling distinct interneuron populations: fast-spiking parvalbumin-positive (PV+) and somatostatin-positive (SST+) interneurons. We use optical stimulation of channelrhodopsin-2 (ChR2) expressing excitatory neurons in layer 2/3 in order to encode a random 1-bit signal in either the synchrony or rate of activity in presynaptic cells. We then examine the mutual information between this 1-bit signal and the voltage and spiking responses in PV+ and SST+ interneurons. Generally, we find that both interneuron types carry more information than GFP negative (GFP-) control cells. More specifically, we find that for a synchrony encoding, PV+ interneurons carry more information in the first 5 milliseconds, while both interneuron subtypes carry more information than negative controls in their later response. We also find that for a rate encoding, SST+ interneurons carry more information than either PV+ or negative controls after several milliseconds. These data demonstrate that inhibitory interneuron subtypes in the neocortex have distinct responses to information carried by synchrony versus rates of spiking.

neuroscience↗