Biology subjects

Taillefumier, T.

Publications and source records attributed to Taillefumier, T..

5 recordsLinked to original sources

bioRxiv2025

Subthreshold variability of neuronal populations driven by synchronous synaptic inputs

Even when driven by the same stimulus, neuronal responses are well-known to exhibit a striking level of spiking variability. In-vivo electrophysiological recordings also reveal a surprisingly large degree of variability at the subthreshold level. In prior work, we considered biophysically relevant neuronal models to account for the observed magnitude of membrane voltage fluctuations. We found that accounting for these fluctuations requires weak but nonzero synchrony in the spiking activity, in amount that are consistent with experimentally measured spiking correlations. Here we investigate whether such synchrony can explain additional statistical features of the measured neural activity, including neuronal voltage covariability and voltage skewness. Addressing this question involves conducting a generalized moment analysis of conductance-based neurons in response to input drives modeled as correlated jump processes. Technically, we perform such an analysis using fixed-point techniques from queuing theory that are applicable in the stationary regime of activity. We found that weak but nonzero synchrony can consistently explain the experimentally reported voltage covariance and skewness. This confirms the role of synchrony as a primary driver of cortical variability and supports that physiological neural activity emerges as a population-level phenomenon, especially in the spontaneous regime. Author summaryOwing to the sheer complexity of biological networks, identifying the design principles for neural computations will only be possible via the simplifying lens of theory. However, to be accepted as valid explanations, theories need to be implemented in idealized neuronal models that can reproduce key aspects of the measured neural activity. Only then can these theories be subjected to experimental validation. In this manuscript, we address this requirement by asking: under which conditions can biophysically relevant neuronal models reproduce physiologically realistic subthreshold activity? We answer this question by focusing on the membrane voltage correlation and skewness, two key statistical signatures of the variable neuronal responses that have been well characterized in behaving mammals. As our core result, we show that the presence of weak but nonzero spiking synchrony is necessary to elicit physiological neuronal responses. The identification of synchrony as a primary driver of neural activity runs counter to the currently prevailing asynchronous state hypothesis, which serves as the basis for many leading neural network theories. Recognizing a central role for synchrony supports that neural computations fundamentally emerge at the collective level rather than as the result of independent parallel processing in neural circuits.

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bioRxiv2024

Synchrony dynamics underlie irregular neocortical spiking

Cortical neurons are characterized by their variable spiking patterns. We challenge prevalent theories for the origin of spiking variability. We examine the specific hypothesis that cortical synchrony drives spiking variability in vivo. Using dynamic clamp, we demonstrate that intrinsic neuronal properties do not contribute substantially to spiking variability, but rather spiking variability emerges from weakly synchronous network drive. With large-scale electrophysiology we quantify the degree of synchrony and its time scale in cortical networks in vivo. We demonstrate that physiological levels of synchrony are sufficient to generate irregular responses found in vivo. Further, this synchrony shifts over timescales ranging from 25 to 200 ms, depending on the presence of external sensory input. Such shifts occur when the network moves from spontaneous to driven modes, leading naturally to a decline in response variability as observed across cortical areas. Finally, while individual neurons exhibit reliable responses to physiological drive, different neurons respond in a distinct fashion according to their intrinsic properties, contributing to stable synchrony across the neural network.

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bioRxiv2023

Exact analysis of the subthreshold variability for conductance-based neuronal models with synchronous synaptic inputs

The spiking activity of neocortical neurons exhibits a striking level of variability, even when these networks are driven by identical stimuli. The approximately Poisson firing of neurons has led to the hypothesis that these neural networks operate in the asynchronous state. In the asynchronous state neurons fire independently from one another, so that the probability that a neuron experience synchronous synaptic inputs is exceedingly low. While the models of asynchronous neurons lead to observed spiking variability, it is not clear whether the asynchronous state can also account for the level of subthreshold membrane potential variability. We propose a new analytical framework to rigorously quantify the subthreshold variability of a single conductance-based neuron in response to synaptic inputs with prescribed degrees of synchrony. Technically we leverage the theory of exchangeability to model input synchrony via jump-process-based synaptic drives; we then perform a moment analysis of the stationary response of a neuronal model with all-or-none conductances that neglects post-spiking reset. As a result, we produce exact, interpretable closed forms for the first two stationary moments of the membrane voltage, with explicit dependence on the input synaptic numbers, strengths, and synchrony. For biophysically relevant parameters, we find that the asynchronous regime only yields realistic subthreshold variability (voltage variance [~=]4-9mV2) when driven by a restricted number of large synapses, compatible with strong thalamic drive. By contrast, we find that achieving realistic subthreshold variability with dense cortico-cortical inputs requires including weak but nonzero input synchrony, consistent with measured pairwise spiking correlations. We also show that without synchrony, the neural variability averages out to zero for all scaling limits with vanishing synaptic weights, independent of any balanced state hypothesis. This result challenges the theoretical basis for mean-field theories of the asynchronous state.

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bioRxiv2021

A structured scaffold underlies activity in the hippocampus

Place cells are believed to organize memory across space and time, inspiring the idea of the cognitive map. Yet unlike the structured activity in the associated grid and head-direction cells, they remain an enigma: their responses have been difficult to predict and are complex enough to be statistically well-described by a random process. Here we report one step toward the ultimate goal of understanding place cells well enough to predict their fields. Within a theoretical framework in which place fields are derived as a conjunction of external cues with internal grid cell inputs, we predict that even apparently random place cell responses should reflect the structure of their grid inputs and that this structure can be unmasked if probed in sufficiently large neural populations and large environments. To test the theory, we design experiments in long, locally featureless spaces to demonstrate that structured scaffolds undergird place cell responses. Our findings, together with other theoretical and experimental results, suggest that place cells build memories of external inputs by attaching them to a largely prespecified grid scaffold.

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bioRxiv2019

Where can a place cell put its fields? Let us count the ways.

A hippocampal place cell exhibits multiple firing fields within and across environments. What factors determine the configuration of these fields, and could they be set down in arbitrary locations? We conceptualize place cells as performing evidence combination across many inputs and selecting a threshold to fire. Thus, mathematically they are perceptrons, except that they act on geometrically organized inputs in the form of multiscale periodic grid-cell drive, and external cues. We analytically count which field arrangements a place cell can realize with structured grid inputs, to show that many more place-field arrangements are realizable with grid-like than one-hot coded inputs. However, the arrangements have a rigid structure, defining an underlying response scaffold. We show that the "separating capacity" or spatial range over which all potential field arrangements are realizable equals the rank of the grid-like input matrix, which in turn equals the sum of distinct grid periods, a small fraction of the unique grid-cell coding range. Learning different grid-to-place weights beyond this small range will alter previous arrangements, which could explain the volatility of the place code. However, compared to random inputs over the same range, grid-structured inputs generate larger margins, conferring relative robustness to place fields when grid input weights are fixed. Significance statementPlace cells encode cognitive maps of the world by combining external cues with an internal coordinate scaffold, but our ability to predict basic properties of the code, including where a place cell will exhibit fields without external cues (the scaffold), remains weak. Here we geometrically characterize the place cell scaffold, assuming it is derived from multiperiodic modular grid cell inputs, and provide exact combinatorial results on the space of permitted field arrangements. We show that the modular inputs permit a large number of place field arrangements, with robust fields, but also strongly constrain their geometry and thus predict a structured place scaffold.

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