Bayesian inference for biophysical neuron models enables stimulus optimization for retinal neuroprosthetics

ABSTRACTMulticompartment models have long been used to study the biophysical mechanisms underlying neural information processing. However, it has been challenging to infer the parameters of such models from data. Here, we build on recent advances in Bayesian simulation-based inference to estimate the parameters of detailed models of retinal neurons whose anatomical structure was based on electron microscopy data. We demonstrate how parameters of a cone, an OFF- and an ON-cone bipolar cell model can be inferred from standard two-photon glutamate imaging with simple light stimuli. The inference method starts with a prior distribution informed by literature knowledge and yields a posterior distribution over parameters highlighting parameters consistent with the data. This posterior allows determining how well parameters are constrained by the data and to what extent changes in one parameter can be compensated for by changes in another. To demonstrate the potential of such data-driven mechanistic neuron models, we created a simulation environment for external electrical stimulation of the retina as used in retinal neuroprosthetic devices. We used the framework to optimize the stimulus waveform to selectively target OFF- and ON-cone bipolar cells, a current major problem of retinal neuroprothetics. Taken together, this study demonstrates how a data-driven Bayesian simulation-based inference approach can be used to estimate parameters of complex mechanistic models with high-throughput imaging data.

A diachronic perspective on peer disagreement in veritistic social epistemology

The main issue in the epistemology of peer disagreement is whether known disagreement among those who are in symmetrical epistemic positions undermines the rationality of their maintaining their respective views. Douven and Kelp have argued convincingly that this problem is best understood as being about how to respond to peer disagreement repeatedly over time, and that this diachronic issue can be best approached through computer simulation. However, Douven and Kelp’s favored simulation framework cannot naturally handle Christensen’s famous Mental Math example. As a remedy, I introduce an alternative (Bayesian) simulation framework, Laputa, inspired by Alvin Goldman’s seminal work on veritistic social epistemology. I show that Christensen’s conciliatory response, reasonably reconstructed and supplemented, gives rise to an increase in epistemic (veritistic) value only if the peers continue to recheck their mental math; else the peers might as well be steadfast. On a meta-level, the study illustrates the power of Goldman’s approach when combined with simulation techniques for handling the computational issues involved.