Past events

Dahlia Kushinsky- Daily normalization of E/I-ratio by light-driven transcription maintains visual processing Abstract: Consistent and reliable encoding of sensory information is essential for an animal’s survival. However, sensory input in an animal’s environment is constantly changing, likely resulting in changes in the brain at the level of molecules, synapses, and cellular circuitry. It is therefore unclear which elements of the system are stable or dynamic, and what mechanisms allow for overall stability of the brain throughout an animal’s life. To address this question, we focused on the visual cortex of adult mice and took advantage of the daily sensory transitions from the dark of night to daylight and back to darkness during a single day. By using RNA-seq, patch clamp slice electrophysiology, and in vivo longitudinal calcium imaging in awake mice, we monitor the light driven changes in molecules, synapses, and cells across a single day. At each of these levels (molecular, synaptic, and cellular), we find rapid sensory-driven increases shortly after transition from darkness to light which is then normalized later in the day. Based on these findings, we suggest that sensory-driven genetic changes maintain functional stability of neural circuits by regulating E/I ratio in excitatory neurons every day. Michael Sokoletsy- Isolated correlates of perception in the posterior cortex Abstract: To uncover the neural mechanisms of stimulus perception, experimenters commonly use tasks in which subjects are repeatedly presented with a weak stimulus and instructed to report, via movement, if they perceived the stimulus. The difference in neural activity between reported stimulus (hit) and unreported stimulus (miss) trials is then seen as potentially perception-related. However, recent studies found that activity related to the report spreads throughout the brain, calling into question to what extent such tasks may be conflating activity that is perception-related with activity that is report-related. To isolate perception-related activity, we developed a paradigm in which the same mice were trained to report either the presence or absence of a whisker stimulus. We found that isolated perception-related activity appeared within a posterio-parietal network of cortical regions contralateral to the stimulus, was on average an order of magnitude lower than the hit versus miss difference, and began just after the low-level stimulus response. In addition, we performed controls to check that it is specifically associated with performance and is not the result of differences in time or uninstructed movements across the tasks. In summary, we revealed for the first time in mice the cortical areas that are associated specifically with the perception of a sensory stimulus and independently of the report.

The immune system and the gut microbiome are becoming major players in chronic neurodegenerative conditions. One of the key interfaces between the brain and the immune system with an impact on brain function is the choroid plexus (CP). The CP interface is central to the maintenance of brain homeostasis by exerting a plethora of different biological processes. However, in aging and Alzheimer’s disease (AD), interferon type-I (IFN-I) signaling accumulates at the CP and impedes part of its beneficial function by inducing a CP-pro-aging signature. My research contributed to the finding that IFN-I signaling at the CP induces an aging-like signature in microglia and impedes cognitive abilities in middle-aged mice in a microglia-dependent manner. In addition, I demonstrated that the brain-specific enzyme, cholesterol 24-hydroxylase (CYP46A1), is expressed by the CP epithelium and that its product, 24-hydroxycholesterol (24-OH), downregulates CP-pro-inflammatory signatures. Furthermore, in AD, CP CYP46A1 protein levels were decreased in both mice and humans and overexpression of Cyp46a1 at the CP in 5xFAD mice reversed brain inflammation, microglial dysfunction signatures, and cognitive loss. Finally, while the pro-inflammatory cytokine TNF-α impaired CP Cyp46a1 expression in vitro, boosting systemic immunity in vivo increased its levels in an IFNGR2-dependent manner. These results highlight CYP46A1 at the CP as a remote regulator of brain inflammation, which diminishes with neurodegeneration, but is amenable to rescue. Focusing on the gut microbiome, I found that 5xFAD mice devoid of microbiome exhibited a striking decrease of long-term spatial memory deficit and increased synaptic and neuronal survival. Spatial memory deficit in 5xFAD mice kept in germ free (GF) or specific-pathogen free (SPF) conditions, negatively correlated with the abundance of 2-hydroxypyridine, while systemic, chronic supply of 2-hydroxypyridine in SPF 5xFAD mice improved spatial memory deficits in comparison to phosphate-buffered saline (PBS)-supplied 5xFAD mice. Overall, these findings demonstrate a microbiome-dependent effect on AD pathology in the 5xFAD mouse model and suggest a connection between 2-hydroxypyridine and AD manifestation. In general, this research thesis addresses novel aspects of choroid plexus and gut microbiome metabolism and their relation to AD progression. Zoom link https://weizmann.zoom.us/j/98658552127?pwd=ZkZmWTBkd1AxZ0xPbGlpU3FPUWpzUT09 Meeting ID:986 5855 2127 Password:495213

Abstract: Brain-computer interfaces (BCI) translate neural activity into movements of a computer cursor or robotic limb. BCIs are known for their ability to assist paralyzed patients. A lesser known, but increasingly important, use of BCIs is their ability to further our basic scientific understanding of brain function. In particular, BCIs are providing insights into the neural mechanisms underlying sensorimotor control that are currently difficult to obtain using limb movements. In this talk, I will demonstrate how a BCI can be leveraged to study how the brain learns. Specifically, I will address why learning some tasks is easier than others, as well as how populations of neurons change their activity in concert during learning. Brief bio: Byron Yu received the B.S. degree in Electrical Engineering and Computer Sciences from the University of California, Berkeley in 2001. He received the M.S. and Ph.D. degrees in Electrical Engineering in 2003 and 2007, respectively, from Stanford University. From 2007 to 2009, he was a postdoctoral fellow jointly in Electrical Engineering and Neuroscience at Stanford University and at the Gatsby Computational Neuroscience Unit, University College London. He then joined the faculty of Carnegie Mellon University in 2010, where he is a Professor in Electrical & Computer Engineering and Biomedical Engineering, and the Gerard G. Elia Career Development Professor. He is broadly interested in how large populations of neurons process information, from encoding sensory stimuli to driving motor actions. His group develops and applies novel statistical algorithms and uses brain-computer interfaces to study brain function. Link- https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421

The architecture of the primate visual system is based on the fovea-fixation-saccade system for high-acuity vision. This talk will describe an analogous system in night vision of monkeys. Processing is based not on the fovea but on a ‘scotopic center’. Unlike the fovea, which is fixed in the retina, the scotopic center relocates over a ‘scotopic band’, according to the intensity of the ambient light and, more generally, perceptual uncertainty. The eye movements involved have sensorimotor transformations specific to night vision. The discussion will touch on the evolution of vision, including relevance for humans. Link: https://weizmann.zoom.us/j/95406893197?pwd=REt5L1g3SmprMUhrK3dpUDJVeHlrZz09 Meeting ID: 954 0689 3197 Password: 750421