Subthreshold variability of neuronal populations driven by synchronous synaptic inputs

Abstract

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.