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

While various forms of cells have been found in relation to the hippocampus cognitive map and navigation system, how these cells are formed and what is read from them is still a mystery. In the current lecture I will talk about several projects which tackle these issues. First, I will show how the formation of border cells in the cognitive map is related to a coordinate transformation, second I will discuss the interaction between the reward system (VTA) and the hippocampus. Finally, I will describe a project using place cells as a proxy for associative memory for assessing deficits in Alzheimer's disease. 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

Fishes have diverged in evolution from the mammalian linage some 450 million years ago and as a result fishes’ brain structure is different from the fundamental design of the mammalian, reptilian and avian brains. This raises the question what can we learn from the ability of fishes to solve different tasks. I will discuss how aspects navigation is implemented in the goldfish brain. Zoom link: https://weizmann.zoom.us/j/96608033618?pwd=SEdJUkR2ZzRBZ3laUUdGbWR1VFJTdz09 Meeting ID: 966 0803 3618 Password: 564068

Diffusion weighted MRI (DWI) is the main neuroimaging modality used in non-invasive investigations of tissue microstructure, and provides quantitative cytomorphological information on a spatial scale well below the nominal resolution of MRI. The main limitation of DWI is its lack of compartmental specificity, as its “reporter molecule” is water, ubiquitous in all tissue compartments and cell types. Brain metabolites are mostly confined to the intracellular space, and their concentrations vary across cell types. Several metabolites give rise to quantifiable magnetic resonance spectroscopy (MRS) signatures, and are thus considered as compartment-specific and sometimes cell-specific markers. Sensitization of MRS to diffusion results in a set of diffusion properties for a variety of intracellular metabolites, from which microstructural information specific to the intracellular space can be obtained. A proper choice of experimental settings can be used to investigate properties that range from cytoplasmic viscosity and tortuosity of the intracellular space, to overall cell morphological features. The specificity of some metabolites to different cell types such as neurons and astrocytes opens the way to studying morphological properties of different cell populations and monitoring their modulation by physiological changes in health and disease. The presentation will introduce methodological concepts of diffusion-weighted MRS, followed by simple examples that demonstrate the unique ability of diffusion-weighted MRS to characterize cell-type specific structural features. Special emphasis will be bestowed on experimental and modelling frameworks that merge the specificity of diffusion-weighted MRS with the sensitivity of DWI to gain insights on tissue microstructure beyond what each method can separately provide. 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

Although animals are known to heavily rely on chemical signals for intraspecies communication, the matter of human chemical communication remains greatly contentious. I will present evidence supporting the claim that humans, just like other animals, rely on bodily-odors to effectively navigate the social world. First, I will present a quantification of people’s overt olfactory-sampling behavior. Of approximately 400 respondents, 94% acknowledged engaging in smelling their close relationships, and approximately 60% acknowledged sniffing strangers. Next, we tested if this olfactory information is employed for socially-relevant behavioral decisions, such as trust, a key element in human socialization. We found that subliminal exposure to body-odor increased implicit trustworthiness attributed to anthropomorphic non-humans. Finally, I will describe the effect of a specific body-volatile, Hexadecanal (HEX), on human impulsive aggression. Using validated behavioral paradigms, we observed a remarkable dissociation: sniffing HEX blocked aggression in men, but triggered aggression in women. Using functional brain imaging, we uncovered a pattern of brain activity mirroring behavior: In both men and women, HEX increased activity in an area implicated in the perception of social cues. Hex then modulated functional connectivity in a brain network implicated in aggressive behavior in a sex-dependent manner. Altogether, the thesis puts forward the hypothesis that chemosignals are a form of human social communication. Under this premise, human sampling behavior of self and others’ body-volatiles provides one with important information that, in turn, affects behaviors central to human society, such as trust and aggression. Zoom link to join: https://weizmann.zoom.us/j/98031517872?pwd=U0EvNG5EdGJBL24zWmpKUlY1akdnZz09 Meeting ID: 980 3151 7872 Password: 976632