Past events

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

Normal brain function involves the interaction of internal processes with incoming sensory stimuli. We have created a series of brain imaging experiments (using 7T fMRI) that sample internal models and feedback mechanisms in early visual cortex. Primary visual cortex (V1) is the entry-stage for cortical processing of visual information. We can show that there are 3 information counter-streams concerned with: (1) retinotopic visual input, (2) top-down predictions of internal models generated by the brain, and (3) top-down imagery acting independently of the perception and prediction loop. Internal models amplify and disamplify incoming information, but there is also mental imagery not interfering with visual perception. Our results speak to the conceptual framework of predictive coding. Healthy brain function will strike a balance between the precision of prediction and prediction update based on prediction error. Our results incorporate state of the art, layer-specific ultra-high field fMRI and other imaging techniques. We argue that fMRI with its capability of measuring dendritic energy consumption is sensitive to activity in different parts of layer spanning neurons, enriching our computational understanding of counter stream brain mechanisms. 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

One of the most remarkable functions of the human brain is the ability to recall a personal experience from the past and reenact it vividly in our mind, in a way that allows us to reflect upon the memory and derive from it relevant information that can guide our future behavior. My doctoral research explored the neuronal mechanisms that enable this core cognitive function in the human brain. Using rare electrophysiological recordings obtained from neurosurgical patients for clinical purposes I investigated and characterized the complex bidirectional interactions that occur between the hippocampus and the cerebral cortex during retrieval of conscious, reportable memories. My results are twofold. I first show that 1-2 seconds before the onset of individual recollections the hippocampus elicits transient electrical oscillations known as Sharp Wave Ripples (SWRs). Such oscillatory events have been extensively studied in animal models in recent years and were shown to reflect massive synchronization events during which millions of pyramidal neurons on the hippocampus output pathway fire simultaneously. My results demonstrate that the SWR events are selective to memory contents and play a major role in coordinating the re-activation of hippocampal-neocortical memory representations during retrieval. I show a tight coupling between SWR events and visual cortex activation, and reveal a massive peri-ripple activation of the default mode network. Second, I show that the cortex uses a flexible, goal-directed, "baseline shift" mechanism that allows the imposition of predefined boundaries on spontaneous recollections. Specifically, the results demonstrate that when free recall is limited to a particular category, the average neuronal activity level in cortical sites that represent the targeted category is steadily and significantly enhanced throughout the free recall period. Such steady-state excitatory enhancement is likely to introduce a category-specific bias in the cortical input arriving at the hippocampus, which may facilitate the reactivation of memory traces belonging to the targeted category and not others. Altogether, the results place hippocampal SWRs firmly as a central mechanism in the retrieval of human declarative memory. They demonstrate a central role for SWRs in coordinating the hippocampus-cortical dialogue during recollection and point to a flexible "baseline shift" mechanism that can account for the remarkable ease and precision by which we can constrain this dialogue to support retrieval goals. Zoom link to join: https://weizmann.zoom.us/j/92146113977?pwd=VmhuMEhBcTRYZDNWMVJ4bGJrR0lIdz09 Meeting ID: 92146113977 Password: 803220

I will discuss two studies from my laboratory, that reveal differential role of hypothalamic paraventricular and supraoptic oxytocin neurons, as well as anterior hypothalamic neurons in social decision making of adult male mice. 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