Untethered firing fields and intermittent silences: Why grid-cell discharge is so variable.

Grid cells in medial entorhinal cortex are notoriously variable in their responses, despite the striking hexagonal arrangement of their spatial firing fields. Indeed, when the animal moves through a firing field, grid cells often fire much more vigorously than predicted or do not fire at all. The source of this trial-to-trial variability is not completely understood. By analyzing grid-cell spike trains from mice running in open arenas and on linear tracks, we characterize the phenomenon of "missed" firing fields using the statistical theory of zero inflation. We find that one major cause of grid-cell variability lies in the spatial representation itself: firing fields are not as strongly anchored to spatial location as the averaged grid suggests. In addition, grid fields from different cells drift together from trial to trial, regardless of whether the environment is real or virtual, or whether the animal moves in light or darkness. Spatial realignment across trials sharpens the grid representation, yielding firing fields that are more pronounced and significantly narrower. These findings indicate that ensembles of grid cells encode relative position more reliably than absolute position.

Grid cells in rat entorhinal cortex encode physical space with independent firing fields and phase precession at the single-trial level.

When a rat moves, grid cells in its entorhinal cortex become active in multiple regions of the external world that form a hexagonal lattice. As the animal traverses one such "firing field," spikes tend to occur at successively earlier theta phases of the local field potential. This phenomenon is called phase precession. Here, we show that spike phases provide 80% more spatial information than spike counts and that they improve position estimates from single neurons down to a few centimeters. To understand what limits the resolution and how variable spike phases are across different field traversals, we analyze spike trains run by run. We find that the multiple firing fields of a grid cell operate as independent elements for encoding physical space. In addition, phase precession is significantly stronger than the pooled-run data suggest. Despite the inherent stochasticity of grid-cell firing, phase precession is therefore a robust phenomenon at the single-trial level, making a theta-phase code for spatial navigation feasible.

Information and efficiency in the nervous system--a synthesis.

In systems biology, questions concerning the molecular and cellular makeup of an organism are of utmost importance, especially when trying to understand how unreliable components--like genetic circuits, biochemical cascades, and ion channels, among others--enable reliable and adaptive behaviour. The repertoire and speed of biological computations are limited by thermodynamic or metabolic constraints: an example can be found in neurons, where fluctuations in biophysical states limit the information they can encode--with almost 20-60% of the total energy allocated for the brain used for signalling purposes, either via action potentials or by synaptic transmission. Here, we consider the imperatives for neurons to optimise computational and metabolic efficiency, wherein benefits and costs trade-off against each other in the context of self-organised and adaptive behaviour. In particular, we try to link information theoretic (variational) and thermodynamic (Helmholtz) free-energy formulations of neuronal processing and show how they are related in a fundamental way through a complexity minimisation lemma.

Resolution of nested neuronal representations can be exponential in the number of neurons.

Collective computation is typically polynomial in the number of computational elements, such as transistors or neurons, whether one considers the storage capacity of a memory device or the number of floating-point operations per second of a CPU. However, we show here that the capacity of a computational network to resolve real-valued signals of arbitrary dimensions can be exponential in N, even if the individual elements are noisy and unreliable. Nested, modular codes that achieve such high resolutions mirror the properties of grid cells in vertebrates, which underlie spatial navigation.

Probable nature of higher-dimensional symmetries underlying mammalian grid-cell activity patterns.

Lattices abound in nature-from the crystal structure of minerals to the honey-comb organization of ommatidia in the compound eye of insects. These arrangements provide solutions for optimal packings, efficient resource distribution, and cryptographic protocols. Do lattices also play a role in how the brain represents information? We focus on higher-dimensional stimulus domains, with particular emphasis on neural representations of physical space, and derive which neuronal lattice codes maximize spatial resolution. For mammals navigating on a surface, we show that the hexagonal activity patterns of grid cells are optimal. For species that move freely in three dimensions, a face-centered cubic lattice is best. This prediction could be tested experimentally in flying bats, arboreal monkeys, or marine mammals. More generally, our theory suggests that the brain encodes higher-dimensional sensory or cognitive variables with populations of grid-cell-like neurons whose activity patterns exhibit lattice structures at multiple, nested scales.

Multiscale codes in the nervous system: the problem of noise correlations and the ambiguity of periodic scales.

Encoding information about continuous variables using noisy computational units is a challenge; nonetheless, asymptotic theory shows that combining multiple periodic scales for coding can be highly precise despite the corrupting influence of noise [Mathis, Herz, and Stemmler, Phys. Rev. Lett. 109, 018103 (2012)]. Indeed, the cortex seems to use periodic, multiscale grid codes to represent position accurately. Here we show how such codes can be read out without taking the long-term limit; even on short time scales, the precision of such codes scales exponentially in the number N of neurons. Does this finding also hold for neurons that are not firing in a statistically independent fashion? To assess the extent to which biological grid codes are subject to statistical dependences, we first analyze the noise correlations between pairs of grid code neurons in behaving rodents. We find that if the grids of two neurons align and have the same length scale, the noise correlations between the neurons can reach values as high as 0.8. For increasing mismatches between the grids of the two neurons, the noise correlations fall rapidly. Incorporating such correlations into a population coding model reveals that the correlations lessen the resolution, but the exponential scaling of resolution with N is unaffected.

Automated optimization of a reduced layer 5 pyramidal cell model based on experimental data.

The construction of compartmental models of neurons involves tuning a set of parameters to make the model neuron behave as realistically as possible. While the parameter space of single-compartment models or other simple models can be exhaustively searched, the introduction of dendritic geometry causes the number of parameters to balloon. As parameter tuning is a daunting and time-consuming task when performed manually, reliable methods for automatically optimizing compartmental models are desperately needed, as only optimized models can capture the behavior of real neurons. Here we present a three-step strategy to automatically build reduced models of layer 5 pyramidal neurons that closely reproduce experimental data. First, we reduce the pattern of dendritic branches of a detailed model to a set of equivalent primary dendrites. Second, the ion channel densities are estimated using a multi-objective optimization strategy to fit the voltage trace recorded under two conditions - with and without the apical dendrite occluded by pinching. Finally, we tune dendritic calcium channel parameters to model the initiation of dendritic calcium spikes and the coupling between soma and dendrite. More generally, this new method can be applied to construct families of models of different neuron types, with applications ranging from the study of information processing in single neurons to realistic simulations of large-scale network dynamics.