Biology subjects

Kaliss, N.

Publications and source records attributed to Kaliss, N..

4 recordsLinked to original sources

bioRxiv2026

Therapeutic targeting of fibrin-microglia interactions ameliorates Alzheimer disease-related hyperexcitability and brain network dysfunction

Brain network dysfunction--including hyperexcitability, altered oscillations, and sleep disruption--is prominent in Alzheimers disease (AD), but the contribution of vascular-neuroimmune processes to these alterations remains unclear. Here, we blocked the pro-inflammatory interaction of the blood protein fibrin with microglia using genetic (Fgg{gamma}390-396A mice) and antibody-based (5B8 and THN392) strategies to test its role in AD-related network dysfunction. The 5xFAD model of AD exhibited network hyperexcitability associated with oscillatory slowing, sleep states, and disrupted sleep-circadian rhythms. These deficits were largely attenuated by blocking fibrin-microglia interactions in 5xFAD;Fgg{gamma}390-396A mice. Notably, pharmacological interventions after disease onset with both anti-fibrin antibodies similarly attenuated these AD-related network deficits and behavioral abnormalities. We conclude that vascular-neuroimmune processes driven by fibrin-microglia interactions promote AD-related network dysfunction and that targeting the fibrin-microglia axis--currently under clinical evaluation with the humanized antibody THN391-- represents a promising therapeutic strategy for AD. There is a companion manuscript submitted to bioRxiv (Yan et al., 2026).110 HIGHLIGHTSO_LIFibrin promotes AD-related network hyperexcitability and oscillatory slowing in 5xFAD mice C_LIO_LIFibrin promotes AD-related disruption of sleep and circadian rhythms in 5xFAD mice C_LIO_LIGenetic blocking of fibrin-microglia interactions rescues AD-related brain network dysfunction C_LIO_LIAnti-fibrin antibodies (5B8 and THN392) show acute and chronic therapeutic benefit C_LI

neuroscience↗

bioRxiv2025

Decoding hidden goal-directed navigational states and their neuronal representations using a novel labyrinth paradigm and probabilistic modeling framework

Goal-directed navigation involves a sequence of planned actions aimed at achieving long-term goals through reinforcement, but detecting hidden states that support this process and their neuronal substrates remains a fundamental challenge. To address this, we developed a complex labyrinth test that mimics naturalistic foraging and implemented a novel hierarchical probabilistic modeling framework, Cognitive Mapping of Planned Actions with State Spaces (CoMPASS). This framework infers a nested state structure, comprising short-term surveillance-ambulation states (Level 1) and long-term goal-oriented navigational states (Level 2). Using CoMPASS, we show that successful navigation in wild-type mice is marked by increased recruitment of both surveillance and goal-oriented states specifically at decision nodes, revealing how sequential behavioral decisions culminate in long-term goals. In contrast, the humanized AppSAA mouse model of Alzheimers disease (AD) exhibited navigational impairments marked by diminished surveillance during decisions, reduced goal-directed states, and increased navigation stochasticity. Importantly, we show that gamma oscillations in the posterior parietal cortex (PPC), a region involved in spatial navigation planning, encode these CoMPASS behavioral states and their dynamic operating modes linking spatial locations to long-term goals. Our findings provide a novel paradigm for assessing hidden goal-directed navigational states and identify gamma oscillations in the PPC as their neural substrates.

neuroscience↗

bioRxiv2023

Post-acute immunological and behavioral sequelae in mice after Omicron infection

Progress in understanding long COVID and developing effective therapeutics is hampered in part by the lack of suitable animal models. Here we used ACE2-transgenic mice recovered from Omicron (BA.1) infection to test for pulmonary and behavioral post-acute sequelae. Through in-depth phenotyping by CyTOF, we demonstrate that naive mice experiencing a first Omicron infection exhibit profound immune perturbations in the lung after resolving acute infection. This is not observed if mice were first vaccinated with spike-encoding mRNA. The protective effects of vaccination against post-acute sequelae were associated with a highly polyfunctional SARS-CoV-2-specific T cell response that was recalled upon BA.1 breakthrough infection but not seen with BA.1 infection alone. Without vaccination, the chemokine receptor CXCR4 was uniquely upregulated on multiple pulmonary immune subsets in the BA.1 convalescent mice, a process previously connected to severe COVID-19. Taking advantage of recent developments in machine learning and computer vision, we demonstrate that BA.1 convalescent mice exhibited spontaneous behavioral changes, emotional alterations, and cognitive-related deficits in context habituation. Collectively, our data identify immunological and behavioral post-acute sequelae after Omicron infection and uncover a protective effect of vaccination against post-acute pulmonary immune perturbations.

microbiology↗

bioRxiv2022

Activity in primate visual cortex is minimally driven by spontaneous movements

Organisms process sensory information in the context of their own moving bodies, an idea referred to as embodiment. This idea is important for developmental neuroscience, and increasingly plays a role in robotics and systems neuroscience. The mechanisms that support such embodiment are unknown, but a manifestation could be the observation in mice of brain-wide neuromodulation, including in the primary visual cortex, driven by task-irrelevant spontaneous body movements. Here we tested this hypothesis in macaque monkeys, a primate model for human vision, by simultaneously recording visual cortex activity and facial and body movements. Activity in the visual cortex (V1, V2, V3/V3A) was associated with the animals own movements, but this modulation was largely explained by the impact of the movements on the retinal image. These results suggest that embodiment in primate vision may be realized by input provided by the eyes themselves.

neuroscience↗