How do we strengthen memories while we sleep? In this talk, I will first focus on the question of how different sleep signatures (slow oscillations, spindles and ripples) interact and facilitate hippocampal-neocortical information transfer. I will then present recent data on actual memory content being reactivated during sleep – both naturally (endogenously) and experimentally (exogenously). Zoom link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

Neuron-glia interactions are key for proper myelination in the brain and for its functionality. To study neuron-glia interaction roles in brain development we focus on the genetic disorder Williams syndrome (WS). WS is a multisystemic neurodevelopmental disorder caused by a de-novo hemizygous deletion of ~26 genes from chromosome 7q11.23. We previously revealed surprising aberrations in myelination and brain development in a novel mouse model for the hypersociability phenotype associated with WS, as a result of a neuronal deletion of the transcription factor Gtf2i, which is one of the genes deleted in WS. In this talk, I will present our recent findings focused on altered white matter and brain development in WS, and discuss potential molecular and cellular explanations for the neurodevelopmental deficits in WS. Specifically, I will present evidence for mitochondrial dysfunction in neurons, and what are the microglial responses to the resultant myelination deficits. Furthermore, to study the implication of our studies from mouse models on human condition, I will show our new data on the altered epigenome of human frontal cortex tissue from WS compared to controls. Finally, I will present our approaches to develop new therapeutic approaches and will update on our clinical trial focused on ameliorating white matter deficits in WS. Hybrid seminar Zoom link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

The human hippocampus plays a crucial role in episodic memory; the who, what, where memories that define our lives. In the rodent, well-defined anatomy and physiology make the structure an ideal model system; amenable to circuit manipulations and observations designed to test hypotheses concerning how memories are formed and used. Here I will present our recent work in mice which combines anatomical characterization, genetic interventions and in vivo recording to address how noncononical inputs and outputs influence information flow in the hippocampus. I will first introduce our study identifying a novelty signaling hub in the hypothalamus – the supramammillary nucleus (SuM). Unique about this region is that it not only responds broadly to novel stimuli, but segregates and selectively routes different types of information to discrete cortical targets, the dentate gyrus (DG) and CA2 fields of the hippocampus, for the modulation of mnemonic processing. Next, I will describe ongoing work focused on how CA2’s output impacts both local and distal circuits, including our identification and characterization of a novel descending glutamatergic projection from CA2 pyramidal cells to PV+ neurons in the MS that can regulate cholinergic tone and hippocampal memory. Zoom link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

As bigger neuroscience datasets are generated with novel observation modalities, so grows the need for computational tools to answer basic questions. What different types of neurons exist in a population? How to sort out neurons from their electric activity? How do neurons process information? I will present statistical, machine learning and information-theoretic tools that address such questions. In particular, I will discuss new solutions to the problem of classifying neuron types using genetic markers, amortizing spike-sorting in modern multi-electrode arrays and disentangling the simultaneous presence of synergy and redundancy in neural information processing circuits.

Sleep is critical for the stabilization of memories. This process is thought to be supported by the reactivation of memories, thereby strengthening the neural infrastructure supporting them. Theoretical accounts of this consolidation process focus on the process through which memories are independently strengthened, but in natural settings individual memories never exist in a vacuum. In this talk, I will present a series of studies exploring the extent of memory reactivation during sleep in humans, how interactions between memories impact the consolidation process, and the role of encoding context in memory processing during sleep. The main technique used to explore memory reactivation in these studies is targeted memory reactivation, a behavioral manipulation that can selectively bias consolidation during sleep. The results demonstrate that multiple semantically related memories can be simultaneously consolidated during sleep. Additionally, they show that memory reactivation during sleep may involve contextual reinstatement, thereby impacting multiple contextually linked memories. These data suggest that reactivation during sleep is not limited to single memory items, and can occur at the network or brain-state level. Relatedly, we show that reactivating a suppression state during sleep can be used to selectively weaken memories. Taken together, these results inform our current understanding regarding memory consolidation processes and open new avenues for translatable research to alleviate memory-related symptoms in patients suffering from psychiatric disorders.

Environmental light intensity affects the nervous system and is a powerful modulator of behavior. Light-intensity-dependent activity is observed in a subset of retinal output cells, which innervate a newly discovered nucleus of the dorsal thalamus, that in turn projects to the prefrontal cortex and striatum. Silencing the transmission along this pathway has been shown to affect mood. I will describe the retinal networks responsible for the transmission of light intensity signals, and show new results demonstrating the capacity for light-intensity encoding in diverse brain regions. Zoom Seminar Zoom Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

: Drug addiction is a chronically relapsing disorder characterized by compulsive drug use despite catastrophic personal consequences (e.g., loss of family, job) and even when the substance is no longer perceived as pleasurable. In this talk, I will present results of human neuroimaging studies, utilizing a multimodal approach (neuropsychology, functional magnetic resonance imaging, event-related potentials recordings), to explore the neurobiology underlying the core psychological impairments in drug addiction (impulsivity, drive/motivation, insight/awareness) as associated with its clinical symptomatology (intoxication, craving, bingeing, withdrawal). The focus of this talk is on understanding the role of the dopaminergic mesocorticolimbic circuit, and especially the prefrontal cortex, in higher-order executive dysfunction (e.g., disadvantageous decision-making such as trading a car for a couple of cocaine hits) in drug addicted individuals. The theoretical model that guides the presented research is called iRISA (Impaired Response Inhibition and Salience Attribution), postulating that abnormalities in the orbitofrontal cortex and anterior cingulate cortex (and other prefrontal cortical regions underlying higher order executive function), as related to dopaminergic dysfunction, contribute to the core clinical symptoms in drug addiction. Specifically, our multi-modality program of research is guided by the underlying working hypothesis that drug addicted individuals disproportionately attribute reward value to their drug of choice at the expense of other potentially but no-longer-rewarding stimuli, with a concomitant decrease in the ability to inhibit maladaptive drug use. In this talk I will also explore whether treatment (as usual) and 6-month abstinence enhance recovery in these brain-behavior compromises in treatment seeking cocaine addicted individuals. Promising neuroimaging studies, which combine pharmacological (i.e., oral methylphenidate, or RitalinTM) and salient cognitive tasks or functional connectivity during resting-state, will be discussed as examples of using neuroimaging in the empirical guidance for the development of effective neurorehabilitation strategies (including cognitive reappraisal, mindfulness, and transcranial direct current stimulation) in drug addiction. Zoom Lindk-https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID 954 0689 3197 Password 750421