Fixational drift is driven by diffusive dynamics in central neural circuitry.

During fixation and between saccades, our eyes undergo diffusive random motion called fixational drift. The role of fixational drift in visual coding and inference has been debated in the past few decades, but the mechanisms that underlie this motion remained unknown. In particular, it has been unclear whether fixational drift arises from peripheral sources, or from central sources within the brain. Here we show that fixational drift is correlated with neural activity, and identify its origin in central neural circuitry within the oculomotor system, upstream to the ocular motoneurons (OMNs). We analyzed a large data set of OMN recordings in the rhesus monkey, alongside precise measurements of eye position, and found that most of the variance of fixational eye drifts must arise upstream of the OMNs. The diffusive statistics of the motion points to the oculomotor integrator, a memory circuit responsible for holding the eyes still between saccades, as a likely source of the motion. Theoretical modeling, constrained by the parameters of the primate oculomotor system, supports this hypothesis by accounting for the amplitude as well as the statistics of the motion. Thus, we propose that fixational ocular drift provides a direct observation of diffusive dynamics in a neural circuit responsible for storage of continuous parameter memory in persistent neural activity. The identification of a mechanistic origin for fixational drift is likely to advance the understanding of its role in visual processing and inference.

Grid-cell modules remain coordinated when neural activity is dissociated from external sensory cues.

The representation of an animal's position in the medial entorhinal cortex (MEC) is distributed across several modules of grid cells, each characterized by a distinct spatial scale. The population activity within each module is tightly coordinated and preserved across environments and behavioral states. Little is known, however, about the coordination of activity patterns across modules. We analyzed the joint activity patterns of hundreds of grid cells simultaneously recorded in animals that were foraging either in the light, when sensory cues could stabilize the representation, or in darkness, when such stabilization was disrupted. We found that the states of different modules are tightly coordinated, even in darkness, when the internal representation of position within the MEC deviates substantially from the true position of the animal. These findings suggest that internal brain mechanisms dynamically coordinate the representation of position in different modules, ensuring that they jointly encode a coherent and smooth trajectory.

Toroidal topology of population activity in grid cells.

The medial entorhinal cortex is part of a neural system for mapping the position of an individual within a physical environment1. Grid cells, a key component of this system, fire in a characteristic hexagonal pattern of locations2, and are organized in modules3 that collectively form a population code for the animal's allocentric position1. The invariance of the correlation structure of this population code across environments4,5 and behavioural states6,7, independent of specific sensory inputs, has pointed to intrinsic, recurrently connected continuous attractor networks (CANs) as a possible substrate of the grid pattern1,8-11. However, whether grid cell networks show continuous attractor dynamics, and how they interface with inputs from the environment, has remained unclear owing to the small samples of cells obtained so far. Here, using simultaneous recordings from many hundreds of grid cells and subsequent topological data analysis, we show that the joint activity of grid cells from an individual module resides on a toroidal manifold, as expected in a two-dimensional CAN. Positions on the torus correspond to positions of the moving animal in the environment. Individual cells are preferentially active at singular positions on the torus. Their positions are maintained between environments and from wakefulness to sleep, as predicted by CAN models for grid cells but not by alternative feedforward models12. This demonstration of network dynamics on a toroidal manifold provides a population-level visualization of CAN dynamics in grid cells.

Locally ordered representation of 3D space in the entorhinal cortex.

As animals navigate on a two-dimensional surface, neurons in the medial entorhinal cortex (MEC) known as grid cells are activated when the animal passes through multiple locations (firing fields) arranged in a hexagonal lattice that tiles the locomotion surface1. However, although our world is three-dimensional, it is unclear how the MEC represents 3D space2. Here we recorded from MEC cells in freely flying bats and identified several classes of spatial neurons, including 3D border cells, 3D head-direction cells, and neurons with multiple 3D firing fields. Many of these multifield neurons were 3D grid cells, whose neighbouring fields were separated by a characteristic distance-forming a local order-but lacked any global lattice arrangement of the fields. Thus, whereas 2D grid cells form a global lattice-characterized by both local and global order-3D grid cells exhibited only local order, creating a locally ordered metric for space. We modelled grid cells as emerging from pairwise interactions between fields, which yielded a hexagonal lattice in 2D and local order in 3D, thereby describing both 2D and 3D grid cells using one unifying model. Together, these data and model illuminate the fundamental differences and similarities between neural codes for 3D and 2D space in the mammalian brain.

A theory of joint attractor dynamics in the hippocampus and the entorhinal cortex accounts for artificial remapping and grid cell field-to-field variability.

The representation of position in the mammalian brain is distributed across multiple neural populations. Grid cell modules in the medial entorhinal cortex (MEC) express activity patterns that span a low-dimensional manifold which remains stable across different environments. In contrast, the activity patterns of hippocampal place cells span distinct low-dimensional manifolds in different environments. It is unknown how these multiple representations of position are coordinated. Here, we develop a theory of joint attractor dynamics in the hippocampus and the MEC. We show that the system exhibits a coordinated, joint representation of position across multiple environments, consistent with global remapping in place cells and grid cells. In addition, our model accounts for recent experimental observations that lack a mechanistic explanation: variability in the firing rate of single grid cells across firing fields, and artificial remapping of place cells under depolarization, but not under hyperpolarization, of layer II stellate cells of the MEC.

Velocity coupling of grid cell modules enables stable embedding of a low dimensional variable in a high dimensional neural attractor.

Grid cells in the medial entorhinal cortex (MEC) encode position using a distributed representation across multiple neural populations (modules), each possessing a distinct spatial scale. The modular structure of the representation confers the grid cell neural code with large capacity. Yet, the modularity poses significant challenges for the neural circuitry that maintains the representation, and updates it based on self motion. Small incompatible drifts in different modules, driven by noise, can rapidly lead to large, abrupt shifts in the represented position, resulting in catastrophic readout errors. Here, we propose a theoretical model of coupled modules. The coupling suppresses incompatible drifts, allowing for a stable embedding of a two-dimensional variable (position) in a higher dimensional neural attractor, while preserving the large capacity. We propose that coupling of this type may be implemented by recurrent synaptic connectivity within the MEC with a relatively simple and biologically plausible structure.

Limits on Spectral Resolution Measurements by Quantum Probes.

The limits of frequency resolution in nano-NMR experiments have been discussed extensively in recent years. It is believed that there is a crucial difference between the ability to resolve a few frequencies and the precision of estimating a single one. Whereas the efficiency of single frequency estimation gradually increases with the square root of the number of measurements, the ability to resolve two frequencies is limited by the specific timescale of the signal and cannot be compensated for by extra measurements. Here we show theoretically and demonstrate experimentally that the relationship between these quantities is more subtle and both are only limited by the Cramér-Rao bound of a single frequency estimation.

An efficient coding theory for a dynamic trajectory predicts non-uniform allocation of entorhinal grid cells to modules.

Grid cells in the entorhinal cortex encode the position of an animal in its environment with spatially periodic tuning curves with different periodicities. Recent experiments established that these cells are functionally organized in discrete modules with uniform grid spacing. Here we develop a theory for efficient coding of position, which takes into account the temporal statistics of the animal's motion. The theory predicts a sharp decrease of module population sizes with grid spacing, in agreement with the trend seen in the experimental data. We identify a simple scheme for readout of the grid cell code by neural circuitry, that can match in accuracy the optimal Bayesian decoder. This readout scheme requires persistence over different timescales, depending on the grid cell module. Thus, we propose that the brain may employ an efficient representation of position which takes advantage of the spatiotemporal statistics of the encoded variable, in similarity to the principles that govern early sensory processing.

Slow diffusive dynamics in a chaotic balanced neural network.

It has been proposed that neural noise in the cortex arises from chaotic dynamics in the balanced state: in this model of cortical dynamics, the excitatory and inhibitory inputs to each neuron approximately cancel, and activity is driven by fluctuations of the synaptic inputs around their mean. It remains unclear whether neural networks in the balanced state can perform tasks that are highly sensitive to noise, such as storage of continuous parameters in working memory, while also accounting for the irregular behavior of single neurons. Here we show that continuous parameter working memory can be maintained in the balanced state, in a neural circuit with a simple network architecture. We show analytically that in the limit of an infinite network, the dynamics generated by this architecture are characterized by a continuous set of steady balanced states, allowing for the indefinite storage of a continuous parameter. In finite networks, we show that the chaotic noise drives diffusive motion along the approximate attractor, which gradually degrades the stored memory. We analyze the dynamics and show that the slow diffusive motion induces slowly decaying temporal cross correlations in the activity, which differ substantially from those previously described in the balanced state. We calculate the diffusivity, and show that it is inversely proportional to the system size. For large enough (but realistic) neural population sizes, and with suitable tuning of the network connections, the proposed balanced network can sustain continuous parameter values in memory over time scales larger by several orders of magnitude than the single neuron time scale.

Theory of nonstationary Hawkes processes.

We expand the theory of Hawkes processes to the nonstationary case, in which the mutually exciting point processes receive time-dependent inputs. We derive an analytical expression for the time-dependent correlations, which can be applied to networks with arbitrary connectivity, and inputs with arbitrary statistics. The expression shows how the network correlations are determined by the interplay between the network topology, the transfer functions relating units within the network, and the pattern and statistics of the external inputs. We illustrate the correlation structure using several examples in which neural network dynamics are modeled as a Hawkes process. In particular, we focus on the interplay between internally and externally generated oscillations and their signatures in the spike and rate correlation functions.

Shaping Neural Circuits by High Order Synaptic Interactions.

Spike timing dependent plasticity (STDP) is believed to play an important role in shaping the structure of neural circuits. Here we show that STDP generates effective interactions between synapses of different neurons, which were neglected in previous theoretical treatments, and can be described as a sum over contributions from structural motifs. These interactions can have a pivotal influence on the connectivity patterns that emerge under the influence of STDP. In particular, we consider two highly ordered forms of structure: wide synfire chains, in which groups of neurons project to each other sequentially, and self connected assemblies. We show that high order synaptic interactions can enable the formation of both structures, depending on the form of the STDP function and the time course of synaptic currents. Furthermore, within a certain regime of biophysical parameters, emergence of the ordered connectivity occurs robustly and autonomously in a stochastic network of spiking neurons, without a need to expose the neural network to structured inputs during learning.

Spatial coding and attractor dynamics of grid cells in the entorhinal cortex.

Recent experiments support the theoretical hypothesis that recurrent connectivity plays a central role within the medial entorhinal cortex, by shaping activity of large neural populations, such that their joint activity lies within a continuous attractor. This conjecture involves dynamics within each population (module) of cells that share the same grid spacing. In addition, recent theoretical works raise a hypothesis that, taken together, grid cells from all modules maintain a sophisticated representation of position with uniquely large dynamical range, when compared with other known neural codes in the brain. To maintain such a code, activity in different modules must be coupled, within the entorhinal cortex or through the hippocampus.

The basal ganglia is necessary for learning spectral, but not temporal, features of birdsong.

Executing a motor skill requires the brain to control which muscles to activate at what times. How these aspects of control-motor implementation and timing-are acquired, and whether the learning processes underlying them differ, is not well understood. To address this, we used a reinforcement learning paradigm to independently manipulate both spectral and temporal features of birdsong, a complex learned motor sequence, while recording and perturbing activity in underlying circuits. Our results uncovered a striking dissociation in how neural circuits underlie learning in the two domains. The basal ganglia was required for modifying spectral, but not temporal, structure. This functional dissociation extended to the descending motor pathway, where recordings from a premotor cortex analog nucleus reflected changes to temporal, but not spectral, structure. Our results reveal a strategy in which the nervous system employs different and largely independent circuits to learn distinct aspects of a motor skill.

Fundamental limits on persistent activity in networks of noisy neurons.

Neural noise limits the fidelity of representations in the brain. This limitation has been extensively analyzed for sensory coding. However, in short-term memory and integrator networks, where noise accumulates and can play an even more prominent role, much less is known about how neural noise interacts with neural and network parameters to determine the accuracy of the computation. Here we analytically derive how the stored memory in continuous attractor networks of probabilistically spiking neurons will degrade over time through diffusion. By combining statistical and dynamical approaches, we establish a fundamental limit on the network's ability to maintain a persistent state: The noise-induced drift of the memory state over time within the network is strictly lower-bounded by the accuracy of estimation of the network's instantaneous memory state by an ideal external observer. This result takes the form of an information-diffusion inequality. We derive some unexpected consequences: Despite the persistence time of short-term memory networks, it does not pay to accumulate spikes for longer than the cellular time-constant to read out their contents. For certain neural transfer functions, the conditions for optimal sensory coding coincide with those for optimal storage, implying that short-term memory may be co-localized with sensory representation.

Bayesian model of dynamic image stabilization in the visual system.

Humans can resolve the fine details of visual stimuli although the image projected on the retina is constantly drifting relative to the photoreceptor array. Here we demonstrate that the brain must take this drift into account when performing high acuity visual tasks. Further, we propose a decoding strategy for interpreting the spikes emitted by the retina, which takes into account the ambiguity caused by retinal noise and the unknown trajectory of the projected image on the retina. A main difficulty, addressed in our proposal, is the exponentially large number of possible stimuli, which renders the ideal Bayesian solution to the problem computationally intractable. In contrast, the strategy that we propose suggests a realistic implementation in the visual cortex. The implementation involves two populations of cells, one that tracks the position of the image and another that represents a stabilized estimate of the image itself. Spikes from the retina are dynamically routed to the two populations and are interpreted in a probabilistic manner. We consider the architecture of neural circuitry that could implement this strategy and its performance under measured statistics of human fixational eye motion. A salient prediction is that in high acuity tasks, fixed features within the visual scene are beneficial because they provide information about the drifting position of the image. Therefore, complete elimination of peripheral features in the visual scene should degrade performance on high acuity tasks involving very small stimuli.

Order and stochastic dynamics in Drosophila planar cell polarity.

Cells in the wing blade of Drosophila melanogaster exhibit an in-plane polarization causing distal orientation of hairs. Establishment of the Planar Cell Polarity (PCP) involves intercellular interactions as well as a global orienting signal. Many of the genetic and molecular components underlying this process have been experimentally identified and a recently advanced system-level model has suggested that the observed mutant phenotypes can be understood in terms of intercellular interactions involving asymmetric localization of membrane bound proteins. Among key open questions in understanding the emergence of ordered polarization is the effect of stochasticity and the role of the global orienting signal. These issues relate closely to our understanding of ferromagnetism in physical systems. Here we pursue this analogy to understand the emergence of PCP order. To this end we develop a semi-phenomenological representation of the underlying molecular processes and define a "phase diagram" of the model which provides a global view of the dependence of the phenotype on parameters. We show that the dynamics of PCP has two regimes: rapid growth in the amplitude of local polarization followed by a slower process of alignment which progresses from small to large scales. We discuss the response of the tissue to various types of orienting signals and show that global PCP order can be achieved with a weak orienting signal provided that it acts during the early phase of the process. Finally we define and discuss some of the experimental predictions of the model.

Stimulus-dependent correlations in threshold-crossing spiking neurons.

We consider a threshold-crossing spiking process as a simple model for the activity within a population of neurons. Assuming that these neurons are driven by a common fluctuating input with gaussian statistics, we evaluate the cross-correlation of spike trains in pairs of model neurons with different thresholds. This correlation function tends to be asymmetric in time, indicating a preference for the neuron with the lower threshold to fire before the one with the higher threshold, even if their inputs are identical. The relationship between these results and spike statistics in other models of neural activity is explored. In particular, we compare our model with an integrate-and-fire model in which the membrane voltage resets following each spike. The qualitative properties of spike cross-correlations, emerging from the threshold-crossing model, are similar to those of bursting events in the integrate-and-fire model. This is particularly true for generalized integrate-and-fire models in which spikes tend to occur in bursts, as observed, for example, in retinal ganglion cells driven by a rapidly fluctuating visual stimulus. The threshold-crossing model thus provides a simple, analytically tractable description of event onsets in these neurons.

Accurate path integration in continuous attractor network models of grid cells.

Grid cells in the rat entorhinal cortex display strikingly regular firing responses to the animal's position in 2-D space and have been hypothesized to form the neural substrate for dead-reckoning. However, errors accumulate rapidly when velocity inputs are integrated in existing models of grid cell activity. To produce grid-cell-like responses, these models would require frequent resets triggered by external sensory cues. Such inadequacies, shared by various models, cast doubt on the dead-reckoning potential of the grid cell system. Here we focus on the question of accurate path integration, specifically in continuous attractor models of grid cell activity. We show, in contrast to previous models, that continuous attractor models can generate regular triangular grid responses, based on inputs that encode only the rat's velocity and heading direction. We consider the role of the network boundary in the integration performance of the network and show that both periodic and aperiodic networks are capable of accurate path integration, despite important differences in their attractor manifolds. We quantify the rate at which errors in the velocity integration accumulate as a function of network size and intrinsic noise within the network. With a plausible range of parameters and the inclusion of spike variability, our model networks can accurately integrate velocity inputs over a maximum of approximately 10-100 meters and approximately 1-10 minutes. These findings form a proof-of-concept that continuous attractor dynamics may underlie velocity integration in the dorsolateral medial entorhinal cortex. The simulations also generate pertinent upper bounds on the accuracy of integration that may be achieved by continuous attractor dynamics in the grid cell network. We suggest experiments to test the continuous attractor model and differentiate it from models in which single cells establish their responses independently of each other.

Grid cells: the position code, neural network models of activity, and the problem of learning.

We review progress on the modeling and theoretical fronts in the quest to unravel the computational properties of the grid cell code and to explain the mechanisms underlying grid cell dynamics. The goals of the review are to outline a coherent framework for understanding the dynamics of grid cells and their representation of space; to critically present and draw contrasts between recurrent network models of grid cells based on continuous attractor dynamics and independent-neuron models based on temporal interference; and to suggest open questions for experiment and theory.

What grid cells convey about rat location.

We characterize the relationship between the simultaneously recorded quantities of rodent grid cell firing and the position of the rat. The formalization reveals various properties of grid cell activity when considered as a neural code for representing and updating estimates of the rat's location. We show that, although the spatially periodic response of grid cells appears wasteful, the code is fully combinatorial in capacity. The resulting range for unambiguous position representation is vastly greater than the approximately 1-10 m periods of individual lattices, allowing for unique high-resolution position specification over the behavioral foraging ranges of rats, with excess capacity that could be used for error correction. Next, we show that the merits of the grid cell code for position representation extend well beyond capacity and include arithmetic properties that facilitate position updating. We conclude by considering the numerous implications, for downstream readouts and experimental tests, of the properties of the grid cell code.