FunSy seminars

A fundamental feature of sleep is that a sensory stimulus does not reliably affect behavior or subjective experience. What mediates such “sensory disconnection”? Do similar processes occur during anesthesia, cognitive lapses, and some neuropsychiatric disorders? In a series of studies in humans and rodents, we compared neuronal responses to identical auditory stimuli across wakefulness and sleep. In A1, early single-neuron spiking responses are largely comparable across wakefulness, natural sleep, and light anesthesia. However, robust differences emerge in downstream high-level regions and late-responding neurons, and in signatures of feedback processing, suggesting that sleep impairs effective cortical connectivity. Next, we show that reduced locus coeruleus-noradrenaline (LC-NE) activity during sleep mediates sensory disconnection. In rodents, the level of ongoing tonic LC activity during sleep anticipates sound-evoked awakenings, while minimal optogenetic LC activation or silencing increases and decreases such awakenings, respectively. In humans, pharmacological manipulation of NE levels modulates sensory perception and late sensory responses, suggesting that NE links sensory awareness to external world events. We are exploring novel methods such as transcutaneous vagal nerve stimulation to modulate LC-NE non-invasively in humans. Finally, I will present recent results on sleep and memory consolidation. In epilepsy patients implanted with depth electrodes we investigate the effects of intracranial electrical closed loop stimulation during sleep on memory and hippocampal-neocortical dialogue at single-neuron resolution.

The analysis of brain network dynamics provides an insightful perspective to analyze the dynamic reconfiguration in brain network structure across species to investigate its role during the loss of consciousness. Recent work has highlighted the importance of the dynamical aspect in understanding the functional relevance of alterations in this network structure to investigate how the brain supports consciousness. In this talk, my idea is to fly over a set of ideas and recent results in order to discuss the problems associated with data analysis in the temporal dimension. I will show convergent and complementary results between different methods of investigating the dynamical aspects of the structure-function relationship during the loss of consciousness in the primate and human brain.

Cognition is flexible. Behaviors can change on a moment-by-moment basis. Such flexibility is thought to rely on the brain’s ability to route information through different networks of brain regions in order to support different cognitive computations. However, the mechanisms that determine which network of brain regions is engaged are unknown. To address this, we combined cortex-wide calcium imaging with high-density electrophysiological recordings in eight cortical and subcortical regions of mice. Different dimensions within the population activity of each brain region were functionally connected with different cortex-wide ‘subspace networks’ of regions. These subspace networks were multiplexed, allowing a brain region to simultaneously interact with multiple independent, yet overlapping, networks. Alignment of neural activity within a region to a specific subspace network dimension predicted how neural activity propagated between regions. Thus, changing the geometry of the neural representation within a brain region could be a mechanism to selectively engage different brain-wide networks to support cognitive flexibility.

The hippocampus and the amygdala are two structures required for emotional memory. While the hippocampus encodes the contextual part of the memory, the amygdala processes its emotional valence. During Non-REM sleep, the hippocampus displays high frequency oscillations called “ripples”. Our early work shows that the suppression of ripples during sleep impairs performance on a spatial task, underlying their crucial role in memory consolidation. We more recently showed that the joint amygdala-hippocampus activity linked to aversive learning is reinstated during the following Non-REM sleep epochs, specifically during ripples. This mechanism potentially sustains the consolidation of aversive associative memories during Non REM sleep. On the other hand, REM sleep is associated with regular 8 Hz theta oscillations, and is believed to play a role in the regulation of emotional reactivity and the consolidation of emotional memories. In particular, the activity of the amygdala during REM sleep is important for emotional regulation, but the underlying physiology is relatively unknown. Unraveling the fine neuronal dynamics related to REM sleep, Non-REM sleep and the transitions between states in the amygdala will further our understanding of the implication of these sleep stages and related brain patterns in emotional processing.