TY - JOUR AB - Although much is known about how single neurons in the hippocampus represent an animal's position, how circuit interactions contribute to spatial coding is less well understood. Using a novel statistical estimator and theoretical modeling, both developed in the framework of maximum entropy models, we reveal highly structured CA1 cell-cell interactions in male rats during open field exploration. The statistics of these interactions depend on whether the animal is in a familiar or novel environment. In both conditions the circuit interactions optimize the encoding of spatial information, but for regimes that differ in the informativeness of their spatial inputs. This structure facilitates linear decodability, making the information easy to read out by downstream circuits. Overall, our findings suggest that the efficient coding hypothesis is not only applicable to individual neuron properties in the sensory periphery, but also to neural interactions in the central brain. AU - Nardin, Michele AU - Csicsvari, Jozsef L AU - Tkačik, Gašper AU - Savin, Cristina ID - 14656 IS - 48 JF - The Journal of Neuroscience TI - The structure of hippocampal CA1 interactions optimizes spatial coding across experience VL - 43 ER - TY - JOUR AB - Sleep plays a key role in preserving brain function, keeping the brain network in a state that ensures optimal computational capabilities. Empirical evidence indicates that such a state is consistent with criticality, where scale-free neuronal avalanches emerge. However, the relationship between sleep, emergent avalanches, and criticality remains poorly understood. Here we fully characterize the critical behavior of avalanches during sleep, and study their relationship with the sleep macro- and micro-architecture, in particular the cyclic alternating pattern (CAP). We show that avalanche size and duration distributions exhibit robust power laws with exponents approximately equal to −3/2 e −2, respectively. Importantly, we find that sizes scale as a power law of the durations, and that all critical exponents for neuronal avalanches obey robust scaling relations, which are consistent with the mean-field directed percolation universality class. Our analysis demonstrates that avalanche dynamics depends on the position within the NREM-REM cycles, with the avalanche density increasing in the descending phases and decreasing in the ascending phases of sleep cycles. Moreover, we show that, within NREM sleep, avalanche occurrence correlates with CAP activation phases, particularly A1, which are the expression of slow wave sleep propensity and have been proposed to be beneficial for cognitive processes. The results suggest that neuronal avalanches, and thus tuning to criticality, actively contribute to sleep development and play a role in preserving network function. Such findings, alongside characterization of the universality class for avalanches, open new avenues to the investigation of functional role of criticality during sleep with potential clinical application.Significance statementWe fully characterize the critical behavior of neuronal avalanches during sleep, and show that avalanches follow precise scaling laws that are consistent with the mean-field directed percolation universality class. The analysis provides first evidence of a functional relationship between avalanche occurrence, slow-wave sleep dynamics, sleep stage transitions and occurrence of CAP phase A during NREM sleep. Because CAP is considered one of the major guardians of NREM sleep that allows the brain to dynamically react to external perturbation and contributes to the cognitive consolidation processes occurring in sleep, our observations suggest that neuronal avalanches at criticality are associated with flexible response to external inputs and to cognitive processes, a key assumption of the critical brain hypothesis. AU - Scarpetta, Silvia AU - Morrisi, Niccolò AU - Mutti, Carlotta AU - Azzi, Nicoletta AU - Trippi, Irene AU - Ciliento, Rosario AU - Apicella, Ilenia AU - Messuti, Giovanni AU - Angiolelli, Marianna AU - Lombardi, Fabrizio AU - Parrino, Liborio AU - Vaudano, Anna Elisabetta ID - 12487 IS - 10 JF - iScience TI - Criticality of neuronal avalanches in human sleep and their relationship with sleep macro- and micro-architecture VL - 26 ER - TY - GEN AU - Rella, Simon AU - Kulikova, Y AU - Minnegalieva, Aygul AU - Kondrashov, Fyodor ID - 14862 IS - Supplement_2 KW - Public Health KW - Environmental and Occupational Health SN - 1101-1262 T2 - European Journal of Public Health TI - Complex vaccination strategies prevent the emergence of vaccine resistance VL - 33 ER - TY - JOUR AB - Alpha oscillations are a distinctive feature of the awake resting state of the human brain. However, their functional role in resting-state neuronal dynamics remains poorly understood. Here we show that, during resting wakefulness, alpha oscillations drive an alternation of attenuation and amplification bouts in neural activity. Our analysis indicates that inhibition is activated in pulses that last for a single alpha cycle and gradually suppress neural activity, while excitation is successively enhanced over a few alpha cycles to amplify neural activity. Furthermore, we show that long-term alpha amplitude fluctuations—the “waxing and waning” phenomenon—are an attenuation-amplification mechanism described by a power-law decay of the activity rate in the “waning” phase. Importantly, we do not observe such dynamics during non-rapid eye movement (NREM) sleep with marginal alpha oscillations. The results suggest that alpha oscillations modulate neural activity not only through pulses of inhibition (pulsed inhibition hypothesis) but also by timely enhancement of excitation (or disinhibition). AU - Lombardi, Fabrizio AU - Herrmann, Hans J. AU - Parrino, Liborio AU - Plenz, Dietmar AU - Scarpetta, Silvia AU - Vaudano, Anna Elisabetta AU - De Arcangelis, Lucilla AU - Shriki, Oren ID - 14402 IS - 10 JF - Cell Reports TI - Beyond pulsed inhibition: Alpha oscillations modulate attenuation and amplification of neural activity in the awake resting state VL - 42 ER - TY - GEN AB - Rhythmical cortical activity has long been recognized as a pillar in the architecture of brain functions. Yet, the dynamic organization of its underlying neuronal population activity remains elusive. Here we uncover a unique organizational principle regulating collective neural dynamics associated with the alpha rhythm in the awake resting-state. We demonstrate that cascades of neural activity obey attenuation-amplification dynamics (AAD), with a transition from the attenuation regime—within alpha cycles—to the amplification regime—across a few alpha cycles—that correlates with the characteristic frequency of the alpha rhythm. We find that this short-term AAD is part of a large-scale, size-dependent temporal structure of neural cascades that obeys the Omori law: Following large cascades, smaller cascades occur at a rate that decays as a power-law of the time elapsed from such events—a long-term AAD regulating brain activity over the timescale of seconds. We show that such an organization corresponds to the "waxing and waning" of the alpha rhythm. Importantly, we observe that short- and long-term AAD are unique to the awake resting-state, being absent during NREM sleep. These results provide a quantitative, dynamical description of the so-far-qualitative notion of the "waxing and waning" phenomenon, and suggest the AAD as a key principle governing resting-state dynamics across timescales. AU - Lombardi, Fabrizio AU - Herrmann, Hans J. AU - Parrino, Liborio AU - Plenz, Dietmar AU - Scarpetta, Silvia AU - Vaudano, Anna Elisabetta AU - de Arcangelis, Lucilla AU - Shriki, Oren ID - 10821 T2 - bioRxiv TI - Alpha rhythm induces attenuation-amplification dynamics in neural activity cascades ER - TY - JOUR AB - Statistical inference is central to many scientific endeavors, yet how it works remains unresolved. Answering this requires a quantitative understanding of the intrinsic interplay between statistical models, inference methods, and the structure in the data. To this end, we characterize the efficacy of direct coupling analysis (DCA)—a highly successful method for analyzing amino acid sequence data—in inferring pairwise interactions from samples of ferromagnetic Ising models on random graphs. Our approach allows for physically motivated exploration of qualitatively distinct data regimes separated by phase transitions. We show that inference quality depends strongly on the nature of data-generating distributions: optimal accuracy occurs at an intermediate temperature where the detrimental effects from macroscopic order and thermal noise are minimal. Importantly our results indicate that DCA does not always outperform its local-statistics-based predecessors; while DCA excels at low temperatures, it becomes inferior to simple correlation thresholding at virtually all temperatures when data are limited. Our findings offer insights into the regime in which DCA operates so successfully, and more broadly, how inference interacts with the structure in the data. AU - Ngampruetikorn, Vudtiwat AU - Sachdeva, Vedant AU - Torrence, Johanna AU - Humplik, Jan AU - Schwab, David J. AU - Palmer, Stephanie E. ID - 11638 IS - 2 JF - Physical Review Research SN - 2643-1564 TI - Inferring couplings in networks across order-disorder phase transitions VL - 4 ER - TY - JOUR AB - Models of transcriptional regulation that assume equilibrium binding of transcription factors have been less successful at predicting gene expression from sequence in eukaryotes than in bacteria. This could be due to the non-equilibrium nature of eukaryotic regulation. Unfortunately, the space of possible non-equilibrium mechanisms is vast and predominantly uninteresting. The key question is therefore how this space can be navigated efficiently, to focus on mechanisms and models that are biologically relevant. In this review, we advocate for the normative role of theory—theory that prescribes rather than just describes—in providing such a focus. Theory should expand its remit beyond inferring mechanistic models from data, towards identifying non-equilibrium gene regulatory schemes that may have been evolutionarily selected, despite their energy consumption, because they are precise, reliable, fast, or otherwise outperform regulation at equilibrium. We illustrate our reasoning by toy examples for which we provide simulation code. AU - Zoller, Benjamin AU - Gregor, Thomas AU - Tkačik, Gašper ID - 12156 IS - 9 JF - Current Opinion in Systems Biology KW - Applied Mathematics KW - Computer Science Applications KW - Drug Discovery KW - General Biochemistry KW - Genetics and Molecular Biology KW - Modeling and Simulation SN - 2452-3100 TI - Eukaryotic gene regulation at equilibrium, or non? VL - 31 ER - TY - JOUR AB - Cell dispersion from a confined area is fundamental in a number of biological processes, including cancer metastasis. To date, a quantitative understanding of the interplay of single cell motility, cell proliferation, and intercellular contacts remains elusive. In particular, the role of E- and N-Cadherin junctions, central components of intercellular contacts, is still controversial. Combining theoretical modeling with in vitro observations, we investigate the collective spreading behavior of colonies of human cancer cells (T24). The spreading of these colonies is driven by stochastic single-cell migration with frequent transient cell-cell contacts. We find that inhibition of E- and N-Cadherin junctions decreases colony spreading and average spreading velocities, without affecting the strength of correlations in spreading velocities of neighboring cells. Based on a biophysical simulation model for cell migration, we show that the behavioral changes upon disruption of these junctions can be explained by reduced repulsive excluded volume interactions between cells. This suggests that in cancer cell migration, cadherin-based intercellular contacts sharpen cell boundaries leading to repulsive rather than cohesive interactions between cells, thereby promoting efficient cell spreading during collective migration. AU - Zisis, Themistoklis AU - Brückner, David AU - Brandstätter, Tom AU - Siow, Wei Xiong AU - d’Alessandro, Joseph AU - Vollmar, Angelika M. AU - Broedersz, Chase P. AU - Zahler, Stefan ID - 10530 IS - 1 JF - Biophysical Journal KW - Biophysics SN - 0006-3495 TI - Disentangling cadherin-mediated cell-cell interactions in collective cancer cell migration VL - 121 ER - TY - JOUR AB - Predicting function from sequence is a central problem of biology. Currently, this is possible only locally in a narrow mutational neighborhood around a wildtype sequence rather than globally from any sequence. Using random mutant libraries, we developed a biophysical model that accounts for multiple features of σ70 binding bacterial promoters to predict constitutive gene expression levels from any sequence. We experimentally and theoretically estimated that 10–20% of random sequences lead to expression and ~80% of non-expressing sequences are one mutation away from a functional promoter. The potential for generating expression from random sequences is so pervasive that selection acts against σ70-RNA polymerase binding sites even within inter-genic, promoter-containing regions. This pervasiveness of σ70-binding sites implies that emergence of promoters is not the limiting step in gene regulatory evolution. Ultimately, the inclusion of novel features of promoter function into a mechanistic model enabled not only more accurate predictions of gene expression levels, but also identified that promoters evolve more rapidly than previously thought. AU - Lagator, Mato AU - Sarikas, Srdjan AU - Steinrueck, Magdalena AU - Toledo-Aparicio, David AU - Bollback, Jonathan P AU - Guet, Calin C AU - Tkačik, Gašper ID - 10736 JF - eLife TI - Predicting bacterial promoter function and evolution from random sequences VL - 11 ER - TY - JOUR AB - Activity of sensory neurons is driven not only by external stimuli but also by feedback signals from higher brain areas. Attention is one particularly important internal signal whose presumed role is to modulate sensory representations such that they only encode information currently relevant to the organism at minimal cost. This hypothesis has, however, not yet been expressed in a normative computational framework. Here, by building on normative principles of probabilistic inference and efficient coding, we developed a model of dynamic population coding in the visual cortex. By continuously adapting the sensory code to changing demands of the perceptual observer, an attention-like modulation emerges. This modulation can dramatically reduce the amount of neural activity without deteriorating the accuracy of task-specific inferences. Our results suggest that a range of seemingly disparate cortical phenomena such as intrinsic gain modulation, attention-related tuning modulation, and response variability could be manifestations of the same underlying principles, which combine efficient sensory coding with optimal probabilistic inference in dynamic environments. AU - Mlynarski, Wiktor F AU - Tkačik, Gašper ID - 12332 IS - 12 JF - PLoS Biology TI - Efficient coding theory of dynamic attentional modulation VL - 20 ER -