Biology subjects

Leparulo, A.

Publications and source records attributed to Leparulo, A..

3 recordsLinked to original sources

bioRxiv2025

The somatosensory barrel cortex controls the spindlethalamocortical oscillation by frequency locking

The sleep spindle is a characteristic oscillation typically observed in NREM sleep and anesthesia. It is generated by a closed-loop thalamocortical circuit that is allegedly contributing to thalamocortical gating, sensory processing and memory consolidation. Yet, the circuit intricacy in terms of electrophysiological neuronal properties and connectivity has so far contributed to hinder a clear understanding of its regulation and function. In this study, we experimentally demonstrate that, when driven by the somatosensory cortex, the spindle circuit behaves as a macroscopic single-frequency self-sustained oscillator. We frequency-modulated cortical inputs to the thalamocortical spindle circuit by periodic microstimulation of the barrel cortex in the anesthetized rat. Cortical spindles exhibited synchronization by frequency locking and not resonance, displaying a characteristic Arnold tongue, a hallmark of the self-sustained oscillator. With a rate model of the barrel cortex-thalamus circuit reproducing the oscillator behavior we show that frequency-locking can govern synchronization under whisking. Significance statementTemporal coordination across neurons (neural synchronization) is believed to be a fundamental mechanism underlying brain information processing. Neural synchornization generates oscillatory signals such as waxing and waning, approximately 10 Hz oscillations occurring during sleep and anaesthesia and known as brain spindles. Spindles are generated by a closed-loop circuit between thalamus and cortex but their function remains unknown. We demonstrate that, similarly to a methronome that adjusts its frequency to the one of an external forcing oscillator, the spindle circuit is controlled by the sensory cortex according to a frequency-locking mechanism. We suggest that frequency-locking within the thalmocortical circuitry represents a flexible frequency-adjustable mechanism tuning the processing of sensory inputs by neural synchronization.

neuroscience↗

bioRxiv2025

Whisker stimulation reinforces a resting-state network in the barrel cortex: nested oscillations and avalanches

The cerebral cortex operates in a state of restless activity, even in the absence of external stimuli. Collective neuronal activities, such as neural avalanches and synchronized oscillations, are also found under rest conditions, and these features have been suggested to support sensory processing, brain readiness for rapid responses, and computational efficiency. The rat barrel cortex and thalamus circuit, with its somatotopic organization for processing sensory inputs from the whiskers, provides a powerful system to explore such interplay. To characterize these resting state circuits, we perform simultaneous multi-electrode recordings in rats barrel cortex and thalamus. During spontaneous activity, oscillations with frequencies centered around 11 Hz are detected concomitantly with slow oscillations below 4 Hz, as well as power-law distributed avalanches. The phase of the lower-frequency oscillation appears to modulate the higher-frequency amplitude, and it has a role in gating avalanche occurrences. We then record neural activity during controlled whisker movements and observe that the 11 Hz barrel circuit active at rest is indeed the one involved in response to whisker stimulation. We finally show how a thalamic-driven firing-rate model can describe the entire phenomenology observed at resting state and predict the response of the barrel cortex to controlled whisker movement, suggesting that the same intrinsic dynamics underlying resting-state activity also shape sensory responses. Author SummaryThe brain is active even in the absence of external stimuli, generating complex patterns of activity that are thought to prepare it for processing incoming information. Two prominent features of this spontaneous activity are rhythmic oscillations and neuronal avalanches--bursts of activity that span a wide range of sizes and durations. However, how these patterns relate to actual sensory processing remains unclear. In this study, we investigated the rat barrel cortex, a well-characterized system for processing tactile information from whiskers. By combining electrophysiological recordings and computational modeling, we found that specific transient oscillations centered around 11 Hz are present during rest and become significantly stronger when the whiskers are stimulated. At the same time, spontaneous activity displays a rich dynamical regime with neuronal avalanches, whose timing is modulated by slower brain rhythms. Importantly, we show that a simple thalamus-driven computational model can reproduce these observations. We thus provide a minimal yet powerful model that suggests that the same rich, intrinsic dynamics underlying resting-state activity also shape sensory responses. Our results support the idea that spontaneous brain activity is not idle, but instead reflects an organized dynamical regime that facilitates efficient processing of sensory inputs.

neuroscience↗

bioRxiv2025

Spontaneous Dynamics Predict the Effects of Targeted Intervention in Hippocampal Neuronal Cultures

Microstimulation is a powerful tool for causal interrogation of neural circuits and for therapeutic neuromodulation. However, predicting network-level responses to focal perturbations remains a major challenge. To address this problem in a tractable manner, we combine experiments on networks of hippocampal neurons cultured on high-density multielectrode arrays with spiking network model simulations. To characterize spontaneous and stimulation-evoked network dynamics, we employ a combination of direct electrophysiological readouts and information-theoretic measures. We find that single-channel stimulation reliably evokes a small set of site-specific, stereotyped network activity patterns. Remarkably, effective connectivity inferred from spontaneous activity captures the spatial organization of perturbation responses, enabling reliable ranking of stimulation-evoked effects across the network. Our spiking network model reproduces these observations and reveals the interplay between short-term synaptic depression and distance-dependent excitatory and inhibitory connectivity in shaping both spontaneous and evoked interactions at different effective scales. Spontaneous activity involves local structural routes, while perturbation-evoked responses engage comparatively longer, polysynaptic pathways. By unifying in silico modeling with experimental measurements, this work links spontaneous network structure to stimulation-evoked dynamics, suggesting that spontaneous effective connectivity may serve as a tractable proxy for stimulation targeting in recurrent circuits, with potential implications for the rational design of neuromodulatory interventions.

neuroscience↗