Biology subjects

Pugliese, S.

Publications and source records attributed to Pugliese, S..

3 recordsLinked to original sources

bioRxiv2023

Dissecting the Functional Organization of the C. elegans Serotonergic System at Whole-Brain Scale

Serotonin controls many aspects of animal behavior and cognition. But how serotonin acts on its diverse receptor types in neurons across the brain to modulate global activity and behavior is unknown. Here, we examine how serotonin release from a feeding-responsive neuron in C. elegans alters brain-wide activity to induce foraging behaviors, like slow locomotion and increased feeding. A comprehensive genetic analysis identifies three core serotonin receptors that collectively induce slow locomotion upon serotonin release and three others that interact with them to further modulate this behavior. The core receptors have different functional roles: some induce behavioral responses to sudden increases in serotonin release, whereas others induce responses to persistent release. Whole-brain calcium imaging reveals widespread serotonin-associated brain dynamics, impacting different behavioral networks in different ways. We map out all sites of serotonin receptor expression in the connectome, which, together with synaptic connectivity, helps predict serotonin-associated brain-wide activity changes. These results provide a global view of how serotonin acts at defined sites across a connectome to modulate brain-wide activity and behavior.

neuroscience↗

bioRxiv2021

Thalamocortical mechanisms regulating the relationship between transient beta events and human tactile perception

Transient neocortical events with high spectral power in the 15-29Hz beta band are among the most reliable predictors of sensory perception. Prestimulus beta event rates in primary somatosensory cortex correlate with sensory suppression, most effectively 100-300ms before stimulus onset. However, the neural mechanisms underlying this perceptual association are unknown. We combined human magnetoencephalography (MEG) measurements with biophysical neural modeling to test potential cellular and circuit mechanisms that underlie observed correlations between prestimulus beta events and tactile detection. Extending prior studies, we found that simulated bursts from higher-order, non-lemniscal thalamus were sufficient to drive beta event generation and to recruit slow supragranular inhibition acting on a 300ms time scale to suppress sensory information. Further analysis showed that the same beta generating mechanism can lead to facilitated perception for a brief period when beta events occur simultaneously with tactile stimulation before inhibition is recruited. These findings were supported by close agreement between model-derived predictions and empirical MEG data. The post-event suppressive mechanism explains an array of studies that associate beta with decreased processing, while the during-event faciliatory mechanism may demand a reinterpretation of the role of beta events in the context of coincident timing.

neuroscience↗

bioRxiv2019

A supragranular nexus for the effects of neocortical beta events on human tactile perception

Transient neocortical events with high spectral power in the 15-29Hz beta band are among the most reliable predictors of sensory perception: High prestimulus beta event rates in primary somatosensory lead to sensory suppression, most effective at 100-300ms prestimulus latency. However, the synaptic and neuronal mechanisms inducing betas perceptual effects have not been completely localized. We combined human MEG with neural modeling designed to account for these macroscale signals to interpret the cellular and circuit mechanisms that underlie the influence of beta on tactile detection. Extending prior studies, we modeled the hypothesis that higher-order thalamic bursts, sufficient for beta event generation in cortex, recruit supragranular GABAB inhibition acting on a 300ms time scale to suppress sensory information. Consistency between model and MEG data supported this hypothesis and led to a further prediction, validated in our data, that stimuli are perceived when beta events occur simultaneously with tactile stimulation. The post-event suppressive mechanism explains an array of studies that associate beta with decreased processing, while the during-event mechanism may demand a reinterpretation of the role of beta events in the context of coincident timing.\n\nSignificance statementSomatosensory beta events - transient 15-29Hz oscillations in electromagnetic recordings - are thought to be generated when \"top-down\" bursts of spikes presumably originating in higher-order thalamus arrive in upper layers of somatosensory cortex. Physiological evidence had shown that the immediate action of these top-down projections should be excitatory; however, after a beta event, sensory perception is noticeably inhibited for approximately 300ms. The source of this post-event sensory suppression, in particular, had been unresolved. Using a detailed computational model of somatosensory cortex, we find evidence for the hypothesis that these bursts couple indirectly to GABAB inhibition in upper layers of cortex, and that beta events first briefly disinhibit sensory relay before a longer period of inhibition.

neuroscience↗