Differences in nonlinearities determine retinal cell types.

Classifying neurons in different types is still an open challenge. In the retina, recent works have taken advantage of the ability to record from a large number of cells to classify ganglion cells into different types based on functional information. Although the first attempts in this direction used the receptive field properties of each cell to classify them, more recent approaches have proposed to cluster ganglion cells directly based on their response to stimuli. These two approaches have not been compared directly. Here, we recorded the responses of a large number of ganglion cells and compared two methods for classifying them into functional groups, one based on the receptive field properties, and the other one using directly their responses to stimuli with various temporal frequencies. We show that the response-based approach allows separation of more types than the receptive field-based method, leading to a better classification. This better granularity is due to the fact that the response-based method takes into account not only the linear part of ganglion cell function but also some of the nonlinearities. A careful characterization of nonlinear processing is thus key to allowing functional classification of sensory neurons.NEW & NOTEWORTHY In the retina, ganglion cells can be classified based on their response to visual stimuli. Although some methods are based on the modeling of receptive fields, others rely on responses to characteristic stimuli. We compared these two classes of methods and show that the latter provides a higher discrimination performance. We also show that this gain arises from the ability to account for the nonlinear behavior of neurons.

All-optical inter-layers functional connectivity investigation in the mouse retina.

We developed a multi-unit microscope for all-optical inter-layers circuits interrogation. The system performs two-photon (2P) functional imaging and 2P multiplexed holographic optogenetics at axially distinct planes. We demonstrated the capability of the system to map, in the mouse retina, the functional connectivity between rod bipolar cells (RBCs) and ganglion cells (GCs) by activating single or defined groups of RBCs while recording the evoked response in the GC layer with cell-type specificity and single-cell resolution. We then used a logistic model to probe the functional connectivity between cell types by deriving the "cellular receptive field" describing how RBCs impact each GC type. With the capability to simultaneously image and control neuronal activity at axially distinct planes, the system enables a precise interrogation of multi-layered circuits. Understanding this information transfer is a promising avenue to dissect complex neural circuits and understand the neural basis of computations.

Optimization of Analytical Potentials for Coarse-Grained Biopolymer Models.

The increasing trend in the recent literature on coarse grained (CG) models testifies their impact in the study of complex systems. However, the CG model landscape is variegated: even considering a given resolution level, the force fields are very heterogeneous and optimized with very different parametrization procedures. Along the road for standardization of CG models for biopolymers, here we describe a strategy to aid building and optimization of statistics based analytical force fields and its implementation in the software package AsParaGS (Assisted Parameterization platform for coarse Grained modelS). Our method is based on the use and optimization of analytical potentials, optimized by targeting internal variables statistical distributions by means of the combination of different algorithms (i.e., relative entropy driven stochastic exploration of the parameter space and iterative Boltzmann inversion). This allows designing a custom model that endows the force field terms with a physically sound meaning. Furthermore, the level of transferability and accuracy can be tuned through the choice of statistical data set composition. The method-illustrated by means of applications to helical polypeptides-also involves the analysis of two and three variable distributions, and allows handling issues related to the FF term correlations. AsParaGS is interfaced with general-purpose molecular dynamics codes and currently implements the "minimalist" subclass of CG models (i.e., one bead per amino acid, Cα based). Extensions to nucleic acids and different levels of coarse graining are in the course.

Minimalist Model for the Dynamics of Helical Polypeptides: A Statistic-Based Parametrization.

Low-resolution models are often used to address macroscopic time and size scales in molecular dynamics simulations of biomolecular systems. Coarse graining is often coupled to knowledge-based parametrization to obtain empirical potentials able to reproduce the system thermodynamic behavior. Here, a minimalist coarse grained (GC) model for the helical structures of proteins is reported. A knowledge-based parametrization strategy is coupled to the explicit inclusion of hydrogen-bonding-related terms, resulting in an accurate reproduction of the structure and dynamics of each single helical type, as well as the internal conformational variables correlation. The proposed strategy of basing the force field terms on real physicochemical interactions is transferable to different secondary structures. Thus, this work, though conclusive for helices, is to be considered the first of a series devoted to the application of the knowledge-based, physicochemical model to extended secondary structures and unstructured proteins.