Past events

How do fleeting molecules and dynamic neural codes enable the conversion of transient stimuli into lasting internal representations? And are there unique strategies to achieve memory on different time scales. Our lab addresses these questions by bridging functional genomics with systems neuroscience to provide cross-disciplinary insights. On one hand, we perform genetic mapping in outbred mice for unbiased discovery of genes, cell types, and circuits relevant for memory across different time scales. In parallel, we develop and apply methodologies to record and manipulate high resolution neural activity from these relevant circuits in the behaving animal. In today’s talk, I will discuss how these approaches have led to new insights into the genetic contributions and long-range circuit dynamics that facilitate both short- and long- term memory.  Zoom Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

For decades, Alzheimer's disease (AD) was perceived as a disease of the neuron alone. However, research advances in recent years have challenged this concept and shed light on the critical roles of other cells within the central nervous system (CNS) and the periphery. Within the CNS, microglia and astrocytes were revealed to be key players in disease progression, while other cell types, such as oligodendrocytes, pericytes, and endothelial cells, remained relatively understudied. In my PhD, I focused on understanding how two non-neuronal cell types, the oligodendroglia in the brain parenchyma and the choroid plexus (CP) epithelium, respond to AD and how they possibly affect pathological processes. My research identified a cellular state of oligodendrocytes that significantly increased in association with brain pathology, which we termed disease-associated oligodendrocytes (DOLs). Oligodendrocytes with DOL signature could also be identified in a mouse model of tauopathy and other neurodegenerative and autoimmune inflammatory conditions, suggesting a common response of oligodendrocytes to severe deviation from homeostasis. In the second part of my PhD, I contributed to a research aiming to investigate the mechanisms underlying the decline of the CP's neuroprotective abilities in the context of AD. We found that exposure of choroid plexus epithelial cultures to 24-hydroxycholesterol (24-OH), the enzymatic product of the brain-specific enzyme cholesterol 24-hydroxylase (CYP46A1), results in downregulation of aging- related transcriptomic signatures-such as Interferon type I (IFN-I) associated inflammation. Moreover, we found that CYP46A1 is constitutively expressed by the CP of humans and mice but is reduced in AD patients and 5xFAD mice. Overexpression of Cyp46a1 at the CP in 5xFAD mice attenuated cognitive loss and brain inflammation. Our results suggest that CP CYP46A1 is an unexpected safeguard against chronic anti-viral-like responses that can be rescued when lost. Overall, my PhD work highlights the significance of studying the fate of non-neuronal cell types in neurodegenerative diseases, in general, and in AD, in particular, and emphasizes the potential of next- generation transcriptomic techniques as a powerful tool to unveil previously unexpected pathways and mechanisms involved in these diseases.  Zoom link-https://weizmann.zoom.us/j/98815291638?pwd=cnZTanhzWkEyYmh4Mjk4OWxHMGE5UT09 Meeting ID:988 1529 1638 Password:880170

The assembly of neural circuits critical for visual system function includes the differentiation of select subtypes of amacrine cells (ACs) and retinal ganglion cells (RGCs), the elaboration of precise connections within the retina among ACs and RGCs, and targeting of RGC axons to their appropriate retino-recipient regions within the CNS. I will consider these events in the context of the mammalian accessory optic system (AOS), which is tuned to detect slow directional motion in order to stabilize images on the retina. This work implicates mutations in certain human genes that encode orthologues of proteins critical for assembling murine AOS circuits in phylogenetically conserved aspects of visual system function.

Neurons in the brain form complex networks of synaptic connections. These elaborate networks define the physical scaffold on which neural activity occurs, and shape the collective dynamics of groups of neurons. In this talk, I will present my work on understanding the structural design principles of neural networks, and the relations between their architecture and their functional properties. First, I will ask what are the structural features that shape the function of neural networks, and show we can learn these features from large ensembles of simulated networks. Second, I will discuss how a strong biological constraint on the structure of neural networks does not incur a computational cost, and may even be functionally beneficial. Third, I will show how we can build connectomes which capture both the structure and the function of real data, using a small number of simple biological features.   Zoom Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

How do fleeting molecules and dynamic neural codes enable the conversion of transient stimuli into lasting internal representations? And are there unique strategies to achieve memory on different time scales. Our lab addresses these questions by bridging functional genomics with systems neuroscience to provide cross-disciplinary insights. On one hand, we perform genetic mapping in outbred mice for unbiased discovery of genes, cell types, and circuits relevant for memory across different time scales. In parallel, we develop and apply methodologies to record and manipulate high resolution neural activity from these relevant circuits in the behaving animal. In today’s talk, I will discuss how these approaches have led to new insights into the genetic contributions and long-range circuit dynamics that facilitate both short- and long- term memory.  Zoom Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

For decades, Alzheimer's disease (AD) was perceived as a disease of the neuron alone. However, research advances in recent years have challenged this concept and shed light on the critical roles of other cells within the central nervous system (CNS) and the periphery. Within the CNS, microglia and astrocytes were revealed to be key players in disease progression, while other cell types, such as oligodendrocytes, pericytes, and endothelial cells, remained relatively understudied. In my PhD, I focused on understanding how two non-neuronal cell types, the oligodendroglia in the brain parenchyma and the choroid plexus (CP) epithelium, respond to AD and how they possibly affect pathological processes. My research identified a cellular state of oligodendrocytes that significantly increased in association with brain pathology, which we termed disease-associated oligodendrocytes (DOLs). Oligodendrocytes with DOL signature could also be identified in a mouse model of tauopathy and other neurodegenerative and autoimmune inflammatory conditions, suggesting a common response of oligodendrocytes to severe deviation from homeostasis. In the second part of my PhD, I contributed to a research aiming to investigate the mechanisms underlying the decline of the CP's neuroprotective abilities in the context of AD. We found that exposure of choroid plexus epithelial cultures to 24-hydroxycholesterol (24-OH), the enzymatic product of the brain-specific enzyme cholesterol 24-hydroxylase (CYP46A1), results in downregulation of aging- related transcriptomic signatures-such as Interferon type I (IFN-I) associated inflammation. Moreover, we found that CYP46A1 is constitutively expressed by the CP of humans and mice but is reduced in AD patients and 5xFAD mice. Overexpression of Cyp46a1 at the CP in 5xFAD mice attenuated cognitive loss and brain inflammation. Our results suggest that CP CYP46A1 is an unexpected safeguard against chronic anti-viral-like responses that can be rescued when lost. Overall, my PhD work highlights the significance of studying the fate of non-neuronal cell types in neurodegenerative diseases, in general, and in AD, in particular, and emphasizes the potential of next- generation transcriptomic techniques as a powerful tool to unveil previously unexpected pathways and mechanisms involved in these diseases.  Zoom link-https://weizmann.zoom.us/j/98815291638?pwd=cnZTanhzWkEyYmh4Mjk4OWxHMGE5UT09 Meeting ID:988 1529 1638 Password:880170

The assembly of neural circuits critical for visual system function includes the differentiation of select subtypes of amacrine cells (ACs) and retinal ganglion cells (RGCs), the elaboration of precise connections within the retina among ACs and RGCs, and targeting of RGC axons to their appropriate retino-recipient regions within the CNS. I will consider these events in the context of the mammalian accessory optic system (AOS), which is tuned to detect slow directional motion in order to stabilize images on the retina. This work implicates mutations in certain human genes that encode orthologues of proteins critical for assembling murine AOS circuits in phylogenetically conserved aspects of visual system function.

Neurons in the brain form complex networks of synaptic connections. These elaborate networks define the physical scaffold on which neural activity occurs, and shape the collective dynamics of groups of neurons. In this talk, I will present my work on understanding the structural design principles of neural networks, and the relations between their architecture and their functional properties. First, I will ask what are the structural features that shape the function of neural networks, and show we can learn these features from large ensembles of simulated networks. Second, I will discuss how a strong biological constraint on the structure of neural networks does not incur a computational cost, and may even be functionally beneficial. Third, I will show how we can build connectomes which capture both the structure and the function of real data, using a small number of simple biological features.   Zoom Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421