Integrated Calendar

Zoom Link: https://weizmann.zoom.us/j/94661424796?pwd=U0Z1YjdsbGUrV29STEZlMVhweUtXUT09




All our cells contain the same genetic information, encoded in the sequence of nucleotides that compose our DNA. The identity of different cells, and their response to different stimuli, is therefore controlled by processes regulating which subset of genes is “expressed” at a specific cell and a specific time. The first step in gene expression regulation is the binding of a special family of proteins, called transcription factors, to specific sequences in regulatory regions in the DNA. Packaging of the DNA into the dense structure of chromatin, and chemical modifications of the DNA, provide the cell with the possibility of dynamically modulating expression but add additional layers of complexity to the process in ways that are not fully understood. In my talk, I will report on our work using single-molecule optical tweezers assays to study how the thermodynamics and kinetics of transcription factor binding are modulated by these different layers of information.
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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 top-down response signatures, suggesting that sleep impairs effective cortical connectivity. We reconcile the apparent discrepancy with the classic “thalamic gating” notion by showing that in contrast to natural sleep, deep anesthesia does lead to attenuation already in A1.
Next, we show that reduced locus coeruleus-noradrenaline (LC-NE) activity during sleep mediates sensory disconnection. We find that in freely behaving rats, LC-NE activity is a key mechanism that determines the likelihood of sensory-evoked awakenings (SEA): the level of ongoing tonic LC activity during sleep anticipates SEAs, while minimal optogenetic LC activation or silencing increases and decreases SEA, 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.
In the last part of the talk I will present recent results on sleep and memory consolidation. Using unilateral olfactory stimulation during sleep we find that ‘local’ targeted memory reactivation (TMR) in human sleep selectively promotes specific memories associated with regional sleep oscillations. 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.

Zoom link to join:
https://weizmann.zoom.us/j/96608033618?pwd=SEdJUkR2ZzRBZ3laUUdGbWR1VFJTdz09

Meeting ID: 966 0803 3618
Password: 564068

Host: Dr. Rita Schmidt rita.schmidt@weizmann.ac.il tel: 9070