Biology subjects

Balasubramanian, V.

Publications and source records attributed to Balasubramanian, V..

9 recordsLinked to original sources

bioRxiv2018

Dynamic self-organized error-correction of grid cells by border cells

Grid cells in the entorhinal cortex are believed to establish their regular, spatially correlated firing patterns by path integration of the animals motion. Mechanisms for path integration, e.g. in attractor network models, predict stochastic drift of grid responses, which is not observed experimentally. We demonstrate a biologically plausible mechanism of dynamic self-organization by which border cells, which fire at environmental boundaries, can correct such drift in grid cells. In our model, experience-dependent Hebbian plasticity during exploration allows border cells to learn connectivity to grid cells. Border cells in this learned network reset the phase of drifting grids. This error-correction mechanism is robust to environmental shape and complexity, including enclosures with interior barriers, and makes distinctive predictions for environmental deformation experiments. Our work demonstrates how diverse cell types in the entorhinal cortex could interact dynamically and adaptively to achieve robust path integration.

neuroscience↗

bioRxiv2018

How a well-adapting immune system remembers

An adaptive agent predicting the future state of an environment must weigh trust in new observations against prior experiences. In this light, we propose a view of the adaptive immune system as a dynamic Bayesian machinery that updates its memory repertoire by balancing evidence from new pathogen encounters against past experience of infection to predict and prepare for future threats. This framework links the observed initial rapid increase of the memory pool early in life followed by a mid-life plateau to the ease of learning salient features of sparse environments. We also derive a modulated memory pool update rule in agreement with current vaccine response experiments. Our results suggest that pathogenic environments are sparse and that memory repertoires significantly decrease infection costs even with moderate sampling. The predicted optimal update scheme maps onto commonly considered competitive dynamics for antigen receptors.

immunology↗

bioRxiv2018

A geometric attractor mechanism for self-organization of entorhinal grid modules

Grid cells in the medial entorhinal cortex (mEC) respond when an animal occupies a periodic lattice of \"grid fields\" in the environment. The grids are organized in modules with spatial periods clustered around discrete values separated by constant ratios reported in the range 1.3-1.8. We propose a mechanism for dynamical self-organization in the mEC that can produce this modular structure. In attractor network models of grid formation, the period of a single module is set by the length scale of recurrent inhibition between neurons. We show that grid cells will instead form a hierarchy of discrete modules if a continuous increase in inhibition distance along the dorso-ventral axis of the mEC is accompanied by excitatory interactions along this axis. Moreover, constant scale ratios between successive modules arise through geometric relationships between triangular grids, whose lattice constants are separated by [Formula], or other ratios. We discuss how the interactions required by our model might be tested experimentally and realized by circuits in the mEC.

neuroscience↗

bioRxiv2018

A competitive binding model predicts nonlinear responses of olfactory receptors to complex mixtures

In color vision, the quantitative rules for mixing lights to make a target color are well understood. By contrast, the rules for mixing odorants to make a target odor remain elusive. A solution to this problem in vision relied on characterizing receptor responses to different wavelengths of light and subsequently relating these responses to perception. In olfaction, experimentally measuring receptor responses to a representative set of complex mixtures is intractable due to the vast number of possibilities. To meet this challenge, we develop a biophysical model that predicts mammalian receptor responses to complex mixtures using responses to single odorants. The dominant nonlinearity in our model is competitive binding (CB): only one odorant molecule can attach to a receptor binding site at a time. This simple framework predicts receptor responses to mixtures of up to twelve monomolecular odorants to within 15% of experimental observations and provides a powerful method for leveraging limited experimental data. Simple extensions of our model describe phenomena such as synergy, overshadowing, and inhibition. We demonstrate that the presence of such interactions can be identified via systematic deviations from the competitive binding model.

neuroscience↗

bioRxiv2018

Environmental adaptation of olfactory receptor distributions

Olfactory receptor usage is highly non-uniform, with some receptor types being orders of magnitude more abundant than others. We propose an explanation for this striking fact: the receptor distribution is tuned to maximally represent information about the olfactory environment in a little-studied regime of efficient coding that is sensitive to the global context of correlated sensor responses. This model predicts further that in mammals, where olfactory sensory neurons are replaced regularly, receptor abundances should continuously adapt to odor statistics. Indeed, experiments have found such changes in response to olfactory experience. These changes are mysteriously context-dependent, with increased exposure to odorants leading variously to increased, decreased or unchanged abundances of activated receptors. We show that efficient coding theory predicts precisely such a context-dependence when sensors are correlated. Finally, we demonstrate simple dynamical rules for neural birth and death processes that might provide a mechanism for receptor abundances to adapt optimally.

neuroscience↗

bioRxiv2017

Environmental deformations dynamically shift the spatial metric of the brain

Environmental deformations induce stereotyped distortions in the time-averaged activity of grid and place cells. We hypothesized that these effects are partly driven by border cell inputs which reset the spatial phase of grid cells, maintaining learned relationships between grid phase and environmental boundaries without altering inherent grid scale. A computational model of this mechanism reproduced diverse distortions during deformations, including scale-dependent and local distortions of grid fields, and stretched, duplicated, and fractured place fields. This model predicted a striking new effect: dynamic, history-dependent, boundary-tethered shifts in grid phase during deformations. We reanalyzed two rodent grid cell rescaling datasets and found direct evidence of these shifts, which have not been previously reported and contribute to the appearance of rescaling. These results demonstrate that the grid representation of geometrically deformed environments is not fixed, but rather dynamically changes with the specific experience of the navigator.

neuroscience↗

bioRxiv2017

Disorder and the neural representation of complex odors: smelling in the real world

Animals smelling in the real world use a small number of receptors to sense a vast number of natural molecular mixtures, and proceed to learn arbitrary associations between odors and valences. Here, we propose a new interpretation of how the architecture of olfactory circuits is adapted to meet these immense complementary challenges. First, the diffuse binding of receptors to many molecules compresses a vast odor space into a tiny receptor space, while preserving similarity. Next, lateral interactions \"densify\" and decorrelate the response, enhancing robustness to noise. Finally, disordered projections from the periphery to the central brain reconfigure the densely packed information into a format suitable for flexible learning of associations and valences. We test our theory empirically using data from Drosophila. Our theory suggests that the neural processing of olfactory information differs from the other senses in its fundamental use of disorder.

neuroscience↗

bioRxiv2017

Cortical neural activity predicts sensory acuity under optogenetic manipulation.

Excitatory and inhibitory neurons in the mammalian sensory cortex form interconnected circuits that control cortical stimulus selectivity and sensory acuity. Theoretical studies have predicted that suppression of inhibition in such excitatory-inhibitory networks can lead to either an increase or, paradoxically, a decrease in excitatory neuronal firing, with consequent effects on stimulus selectivity. We tested whether modulation of inhibition or excitation in the auditory cortex could evoke such a variety of effects in tone-evoked responses and in behavioral frequency discrimination acuity. We found that, indeed, the effects of optogenetic manipulation on stimulus selectivity and behavior varied in both magnitude and sign across subjects, possibly reflecting differences in circuitry or expression of optogenetic factors. Changes in neural population responses consistently predicted behavioral changes for individuals separately, including improvement and impairment in acuity. This correlation between cortical and behavioral change demonstrates that, despite complex and varied effects these manipulations can have on neuronal dynamics, the resulting changes in cortical activity account for accompanying changes in behavioral acuity.\n\nAuthor summaryExcitatory and inhibitory interactions determine stimulus specificity and tuning in sensory cortex, thereby controlling perceptual discrimination acuity. Modeling of such excitatory-inhibitory circuits has predicted that suppressing the activity of inhibitory neurons can lead to increases or, paradoxically, decreases in excitatory activity, depending on the architecture and modulation parameters of the inhibitory component of the network. Here, we capitalized on differences between subjects to test whether suppressing/activating inhibition and excitation across a range of parameters in sensory cortex can in fact exhibit such paradoxical effects for both stimulus sensitivity and behavioral discriminability. Indeed, we found that the same optogenetic manipulation in the auditory cortices of different mice could improve or impair frequency discrimination acuity, in a fashion that was predictable from the effects on cortical responses to tones. The same manipulations sometimes produced opposite changes in the behavior of different individuals, supporting theoretical predictions for inhibition-stabilized networks.

neuroscience↗

bioRxiv2016

Complete coverage of space favors modularity of the grid system in the brain

Grid cells in the entorhinal cortex fire when animals that are exploring a certain region of space occupy the vertices of a triangular grid that spans the environment. Different neurons feature triangular grids that differ in their properties of periodicity, orientation and ellipticity. Taken together, these grids allow the animal to maintain an internal, mental representation of physical space. Experiments show that grid cells are modular, i.e. there are groups of neurons which have grids with similar periodicity, orientation and ellipticity. We use statistical physics methods to derive a relation between variability of the properties of the grids within a module and the range of space that can be covered completely (i.e. without gaps) by the grid system with high probability. Larger variability shrinks the range of representation, providing a functional rationale for the experimentally observed co-modularity of grid cell periodicity, orientation and ellipticity. We obtain a scaling relation between the number of neurons and the period of a module, given the variability and coverage range. Specifically, we predict how many more neurons are required at smaller grid scales than at larger ones.

neuroscience↗