VIDEO ABSTRACT.

At many scales in neuroscience, appropriate mathematical models take the form of complex dynamical systems. Parameterizing such models to conform to the multitude of available experimental constraints is a global non-linear optimisation problem with a complex fitness landscape, requiring numerical techniques to find suitable approximate solutions. Stochastic optimisation approaches, such as evolutionary algorithms, have been shown to be effective, but often the setting up of such optimisations and the choice of a specific search algorithm and its parameters is non-trivial, requiring domain-specific expertise. Here we describe BluePyOpt, a Python package targeted at the broad neuroscience community to simplify this task. BluePyOpt is an extensible framework for data-driven model parameter optimisation that wraps and standardizes several existing open-source tools. It simplifies the task of creating and sharing these optimisations, and the associated techniques and knowledge. This is achieved by abstracting the optimisation and evaluation tasks into various reusable and flexible discrete elements according to established best-practices. Further, BluePyOpt provides methods for setting up both small- and large-scale optimisations on a variety of platforms, ranging from laptops to Linux clusters and cloud-based compute infrastructures. The versatility of the BluePyOpt framework is demonstrated by working through three representative neuroscience specific use cases.

Every neuron is part of a network, exerting its function by transforming multiple spatiotemporal synaptic input patterns into a single spiking output. This function is specified by the particular shape and passive electrical properties of the neuronal membrane, and the composition and spatial distribution of ion channels across its processes. For a variety of physiological or pathological reasons, the intrinsic input/output function may change during a neuron’s lifetime. This process results in high variability in the peak specific conductance of ion channels in individual neurons. The mechanisms responsible for this variability are not well understood, although there are clear indications from experiments and modeling that degeneracy and correlation among multiple channels may be involved. Here, we studied this issue in biophysical models of hippocampal CA1 pyramidal neurons and interneurons. Using a unified data-driven simulation workflow and starting from a set of experimental recordings and morphological reconstructions obtained from rats, we built and analyzed several ensembles of morphologically and biophysically accurate single cell models with intrinsic electrophysiological properties consistent with experimental findings. The results suggest that the set of conductances expressed in any given hippocampal neuron may be considered as belonging to two groups: one subset is responsible for the major characteristics of the firing behavior in each population and the other is responsible for a robust degeneracy. Analysis of the model neurons suggests several experimentally testable predictions related to the combination and relative proportion of the different conductances that should be expressed on the membrane of different types of neurons for them to fulfill their role in the hippocampus circuitry.

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Central vestibular neurons receive substantial inputs from the contralateral labyrinth through inhibitory and excitatory brainstem commissural pathways. The functional organization of these pathways was studied by a multi-methodological approach in isolated frog whole brains. Retrogradely labeled vestibular commissural neurons were primarily located in the superior vestibular nucleus in rhombomeres 2/3 and the medial and descending vestibular nucleus in rhombomeres 5-7. Restricted projections to contralateral vestibular areas, without collaterals to other classical vestibular targets, indicate that vestibular commissural neurons form a feedforward pushpull circuitry. Electrical stimulation of the contralateral coplanar semicircular canal nerve evoked in canal-related second-order vestibular neurons (2°VN) commissural IPSPs (ϳ70%) and EPSPs (ϳ30%) with mainly (ϳ70%) disynaptic onset latencies. The dynamics of commissural responses to electrical pulse trains suggests mediation predominantly by tonic vestibular neurons that activate in all tonic 2°VN large-amplitude IPSPs with a reversal potential of Ϫ74 mV. In contrast, phasic 2°VN exhibited either nonreversible, smallamplitude IPSPs (ϳ40%) of likely dendritic origin or large-amplitude commissural EPSPs (ϳ60%). IPSPs with disynaptic onset latencies were exclusively GABAergic (mainly GABA A receptor-mediated) but not glycinergic, compatible with the presence of GABAimmunopositive (ϳ20%) and the absence of glycine-immunopositive vestibular commissural neurons. In contrast, IPSPs with longer, oligosynaptic onset latencies were GABAergic and glycinergic, indicating that both pharmacological types of local inhibitory neurons were activated by excitatory commissural fibers. Conservation of major morpho-physiological and pharmacological features of the vestibular commissural pathway suggests that this phylogenetically old circuitry plays an essential role for the processing of bilateral angular head acceleration signals in vertebrates.