Multi-compartment Hodgkin-Huxley models are biophysical models of how electrical signals propagate throughout a neuron, and they form the basis of our knowledge of neural computation at the cellular level. However, these models have many free parameters that must be estimated for each cell, and existing fitting methods rely on intracellular voltage measurements that are highly challenging to obtain in vivo. Recent advances in neural recording technology with high-density probes and arrays enable dense sampling of extracellular voltage from many sites surrounding a neuron, allowing indirect measurement of many compartments of a cell simultaneously. Here, we propose a method for inferring the underlying membrane voltage, biophysical parameters, and the neuron's position relative to the probe, using extracellular measurements alone. We use an Extended Kalman Filter to infer membrane voltage and channel states using efficient, differentiable simulators. Then, we learn the model parameters by maximizing the marginal likelihood using gradient-based methods. We demonstrate the performance of this approach using simulated data and real neuron morphologies.

We propose a Koopman-enhanced physics-informed neural network (K--PINN) framework for parameter inference and forecasting in nonlinear epidemic models. This method combines Koopman operator theory and physics-informed learning. It maps epidemic states into a latent observable space where the dynamics evolve approximately linearly while satisfying the governing epidemic equations through automatic differentiation. This integration improves interpretability, parameter identifiability, and long-term predictive stability. We apply the proposed framework to a normalized SEIRSD epidemic model and evaluate it using synthetic monkeypox (Mpox) data and real-world datasets from Germany, Morocco, and Sweden for the SARS-CoV-2 virus. Synthetic trajectories are generated using a structure-preserving, nonstandard finite difference scheme to ensure reliable training data. Numerical results demonstrate that K--PINN achieves more accurate parameter estimation, trajectory reconstruction, and long-term forecasting than classical PINNs and Koopman-EDMD approaches. These results suggest that K--PINN is an effective machine learning framework for epidemic modeling that can be extended to more complex systems.

Physics-Informed Neural Networks (PINNs) are an attractive tool for partial-observation problems in biology, where the governing dynamics are known but some compartments cannot be measured. Chemotherapy pharmacokinetics (PK) is a clean instance: drug concentration in plasma is routinely measured, but concentration in tissue -- which determines tumour kill and off-target toxicity -- is not. We benchmark a PINN against the standard clinical baseline (nonlinear least-squares on the analytical biexponential plasma solution, hereafter NLS) and a physics-agnostic neural baseline (a data-only MLP) on two PK problems. On the linear two-compartment problem, NLS is near-optimal; the PINN matches it to within a small constant factor while also producing the tissue curve in a single training pass, whereas the data-only MLP fails on tissue by roughly 10x. On a Michaelis-Menten extension (saturable elimination), the biexponential closed form no longer exists, so NLS is mis-specified and silently returns meaningless rate constants. The PINN instead exposes a deeper fact: the Michaelis-Menten two-compartment model is non-identifiable from plasma alone, and the PINN reports this honestly by converging to a basin with k12 -> 0. Adding two sparse tissue observations largely resolves identifiability: across five seeds the PINN recovers k21 to within 1% of truth and Vmax, Km to within one standard-deviation bar, while k12 moves in the correct direction (0.02 -> 0.82) but remains ~2 sigma below truth -- a recovery the closed-form NLS estimator cannot attempt at all, because its biexponential ansatz describes only plasma. Our claim is not that PINNs beat NLS. It is that PINNs offer a uniform recipe that ties the textbook estimator on the textbook problem, exposes structural identifiability that the textbook estimator hides, and absorbs heterogeneous measurements within a single loss.

Donor-level disease classification from single-cell RNA sequencing (scRNA-seq) requires strict donor-aware cross-validation: naive pipelines that split cells randomly conflate training and test donors, inflating reported performance through pseudoreplication. We present a donor-aware benchmark evaluating three feature representations across two independent IBD cohorts: centered log-ratio (CLR) transformed cell-type composition, GatedStructuralCFN dependency embeddings, and scVI variational autoencoder latent embeddings. The cohorts are the SCP259 ulcerative colitis atlas (UC vs. Healthy, n=30 donors, 51 cell types) and the Kong 2023 Crohn's disease atlas (CD vs. Healthy, n=71 donors, 55-68 cell types across three intestinal regions). Compartment-stratified CLR composition achieves AUROC 0.956 +/- 0.061 on SCP259; GatedStructuralCFN on the same features achieves 0.978 +/- 0.050. In the Kong cohort, CFN achieves its best performance in the colon region (0.960 +/- 0.055 after feature filtering), exceeding linear CLR (0.900 +/- 0.100), while terminal ileum classification is dominated by linear models (CatBoost CLR 0.967 +/- 0.075 vs. CFN 0.811 +/- 0.164). Cross-dataset transfer (CD->UC, four shared cell types) achieves AUC 0.833 with XGBoost CLR; the reverse direction performs at chance. CFN edge stability analysis shows that compartment-wise composition eliminates spurious unit-sum-induced instability present in global composition (Jaccard 0.026 vs. top-20 recurrence 1.0). CFN shows a consistent numerical advantage over linear models in the colon region of CD (AUROC 0.960 vs. 0.900), though no inter-method comparison reached statistical significance at n<=34 donors per region. Compartment-aware feature construction is critical for both classification performance and structural interpretability. Code: https://github.com/Jonathan-321/sfn-scrna-study

Dendritic updates Complete versions of the dendritic update rules (summarised in Eqns (2) & (3)) are given below. This is valid in our regime where the environmental latent updates slowly compared to neural timescales. The notation we're using admits the possible presence of biases as well as the weights (though biases typically aren't used) by assuming a row of constant 1's could be added to the synaptic inputs effectively absorbing a bias into the weight matrix without loss of generality, for example wgB p(t) wgB p(t)+ bgB . Somatic updates Somatic updates rules (Eqns (4) & (5)) and are repeated here for completeness: p(t)= (t)pB(t)+(1 (t))pA(t) g(t)= (t)gB(t)+(1 (t))gA(t). Update ordering For this hierarchical network of multicompartmental neurons we must specify the order in which we perform these discrete updates to the different layers and the different compartments within these layers.

Advances in generative models have recently revolutionised machine learning. Meanwhile, in neuroscience, generative models have long been thought fundamental to animal intelligence. Understanding the biological mechanisms that support these processes promises to shed light on the relationship between biological and artificial intelligence. In animals, the hippocampal formation is thought to learn and use a generative model to support its role in spatial and non-spatial memory. Here we introduce a biologically plausible model of the hippocampal formation tantamount to a Helmholtz machine that we apply to a temporal stream of inputs. A novel component of our model is that fast theta-band oscillations (5-10 Hz) gate the direction of information flow throughout the network, training it akin to a high-frequency wake-sleep algorithm. Our model accurately infers the latent state of high-dimensional sensory environments and generates realistic sensory predictions. Furthermore, it can learn to path integrate by developing a ring attractor connectivity structure matching previous theoretical proposals and flexibly transfer this structure between environments.

Fast, stealthy, and cheap--autonomous, semisubmersible drone boats carrying tons of cocaine could be international law enforcement's nightmare scenario. A big one just came ashore. Colombian military officials intercepted this 40-foot-long uncrewed fiberglass "narco sub" in the ocean just off Tayrona National Park. On a bright morning last April, a surveillance plane operated by the Colombian military spotted a 40-foot-long shark-like silhouette idling in the ocean just off Tayrona National Park. It was, unmistakably, a "narco sub," a stealthy fiberglass vessel that sails with its hull almost entirely underwater, used by drug cartels to move cocaine north. The plane's crew radioed it in, and eventually nearby coast guard boats got the order, routine but urgent: Intercept. In Cartagena, about 150 miles from the action, Captain Jaime González Zamudio, commander of the regional coast guard group, sat down at his desk to watch what happened next.

Recent progress in the development of voltage indicators [1-8] has brought us closer to a longstanding goal incellular neuroscience: imaging the full spatiotemporal voltageonadendritic tree. These recordings have the potential (pun not intended) to resolve fundamental questions about the computations performed by dendrites -- questions that have remained open for more than a century[9,10].

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Modern recording techniques now allow us to record from distinct neuronal populations in different brain networks.