Neural Information Processing Systems http://nips.cc/

Neural Information Processing Systems http://nips.cc/

The inherent noise of neural systems makes it difficult to construct models which accurately capture experimental measurements of their activity. While much research has been done on how to efficiently model neural activity with descriptive models such as linear-nonlinear-models (LN), Bayesian inference for mechanistic models has received considerably less attention. One reason for this is that these models typically lead to intractable likelihoods and thus make parameter inference difficult. Here, we develop an approximate Bayesian inference scheme for a fully stochastic, biophysically inspired model of glutamate release at the ribbon synapse, a highly specialized synapse found in different sensory systems. The model translates known structural features of the ribbon synapse into a set of stochastically coupled equations. We approximate the posterior distributions by updating a parametric prior distribution via Bayesian updating rules and show that model parameters can be efficiently estimated for synthetic and experimental data from in vivo two-photon experiments in the zebrafish retina. Also, we find that the model captures complex properties of the synaptic release such as the temporal precision and outperforms a standard GLM. Our framework provides a viable path forward for linking mechanistic models of neural activity to measured data.

Neurons in early sensory areas rapidly adapt to changing sensory statistics, both by normalizing the variance of their individual responses and by reducing correlations between their responses. Together, these transformations may be viewed as an adaptive form of statistical whitening. Existing mechanistic models of adaptive whitening exclusively use either synaptic plasticity or gain modulation as the biological substrate for adaptation; however, on their own, each of these models has significant limitations. In this work, we unify these approaches in a normative multi-timescale mechanistic model that adaptively whitens its responses with complementary computational roles for synaptic plasticity and gain modulation. Gains are modified on a fast timescale to adapt to the current statistical context, whereas synapses are modified on a slow timescale to match structural properties of the input statistics that are invariant across contexts. Our model is derived from a novel multi-timescale whitening objective that factorizes the inverse whitening matrix into basis vectors, which correspond to synaptic weights, and a diagonal matrix, which corresponds to neuronal gains. We test our model on synthetic and natural datasets and find that the synapses learn optimal configurations over long timescales that enable adaptive whitening on short timescales using gain modulation.

Mechanistic models of single-neuron dynamics have been extensively studied in computational neuroscience. However, identifying which models can quantitatively reproduce empirically measured data has been challenging. We propose to overcome this limitation by using likelihood-free inference approaches (also known as Approximate Bayesian Computation, ABC) to perform full Bayesian inference on single-neuron models. Our approach builds on recent advances in ABC by learning a neural network which maps features of the observed data to the posterior distribution over parameters. We learn a Bayesian mixture-density network approximating the posterior over multiple rounds of adaptively chosen simulations. Furthermore, we propose an efficient approach for handling missing features and parameter settings for which the simulator fails, as well as a strategy for automatically learning relevant features using recurrent neural networks. On synthetic data, our approach efficiently estimates posterior distributions and recovers ground-truth parameters. On in-vitro recordings of membrane voltages, we recover multivariate posteriors over biophysical parameters, which yield model-predicted voltage traces that accurately match empirical data. Our approach will enable neuroscientists to perform Bayesian inference on complex neuron models without having to design model-specific algorithms, closing the gap between mechanistic and statistical approaches to single-neuron modelling.

Neural Information Processing Systems http://nips.cc/

Neural Information Processing Systems http://nips.cc/

Hematotoxicity, drug-induced damage to the blood-forming system, is a frequent side effect of cytotoxic chemotherapy and poses a significant challenge in clinical practice due to its high inter-patient variability and limited predictability. Current mechanistic models often struggle to accurately forecast outcomes for patients with irregular or atypical trajectories. In this study, we develop and compare hybrid mechanistic and data-driven approaches for individualized time series modeling of platelet counts during chemotherapy. We consider hybrid models that combine mechanistic models with neural networks, known as universal differential equations. As a purely data-driven alternative, we utilize a nonlinear autoregressive exogenous model using gated recurrent units as the underlying architecture. These models are evaluated across a range of real patient scenarios, varying in data availability and sparsity, to assess predictive performance. Our findings demonstrate that data-driven methods, when provided with sufficient data, significantly improve prediction accuracy, particularly for high-risk patients with irregular platelet dynamics. This highlights the potential of data-driven approaches in enhancing clinical decision-making. In contrast, hybrid and mechanistic models are superior in scenarios with limited or sparse data. The proposed modeling and comparison framework is generalizable and could be extended to predict other treatment-related toxicities, offering broad applicability in personalized medicine.