A5049328994- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- RNA modifications and cancer
- Cancer Cells and Metastasis
- Neural dynamics and brain function
- Alzheimer's disease research and treatments
- Stress Responses and Cortisol
- Ferroptosis and cancer prognosis
- Cancer, Hypoxia, and Metabolism
- Sleep and Wakefulness Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Photoreceptor and optogenetics research
- Neurogenesis and neuroplasticity mechanisms
- Zebrafish Biomedical Research Applications
- Lung Cancer Treatments and Mutations
- Cancer Research and Treatments
- Cytokine Signaling Pathways and Interactions
- Stroke Rehabilitation and Recovery
- Nicotinic Acetylcholine Receptors Study
- Cholinesterase and Neurodegenerative Diseases
- Wildlife Ecology and Conservation
- Mental Health Research Topics
- Epigenetics and DNA Methylation
- Musicology and Musical Analysis
- Nuclear Receptors and Signaling
University of Washington
2022-2025
University of California, San Francisco
2014-2024
Howard Hughes Medical Institute
2016-2023
The University of Texas at Austin
2023
Gladstone Institutes
2012-2017
Stanford University
2010-2012
Palo Alto University
2012
Apolipoprotein E4 (apoE4) plays a major role in the pathogenesis of Alzheimer's disease. Brain amyloid-β (Aβ) accumulation depends on age and apoE isoforms (apoE4 > apoE3) both humans transgenic mouse models. levels are also isoform dependent, but opposite direction < apoE3). Thus, one prevailing hypothesis is to increase brain expression reduce Aβ levels. To test this hypothesis, we generated mutant human amyloid precursor protein mice expressing or two copies APOE3 APOE4 gene that...
KRAS is one of the most frequently mutated human oncogenes. In some settings, oncogenic can trigger cellular senescence, whereas in others it produces hyperproliferation. Elucidating mechanisms regulating these 2 drastically distinct outcomes would help identify novel therapeutic approaches RAS-driven cancers. Using a combination functional genomics and mouse genetics, we identified role for transcription factor Wilms tumor 1 (WT1) as critical regulator senescence proliferation downstream...
Excitatory and inhibitory balance of neuronal network activity is essential for normal brain function may be particular importance to memory. Apolipoprotein (apo) E4 amyloid-β (Aβ) peptides, two major players in Alzheimer's disease (AD), cause interneuron impairments aberrant the hippocampal dentate gyrus AD-related mouse models humans, leading learning memory deficits. To determine whether replacing lost or impaired interneurons rescues signaling behavioral deficits, we transplanted...
Representations related to past experiences play a critical role in memory and decision-making processes. The rat hippocampus expresses these types of representations during sharp-wave ripple (SWR) events, previous work identified minority SWRs that contain 'replay' spatial trajectories at ∼20x the movement speed animal. Efforts understand replay typically make multiple assumptions about which events examine what sorts constitute replay. We therefore lack clear understanding both prevalence...
Abstract The hippocampus is a mammalian brain structure that expresses spatial representations 1 and crucial for navigation 2,3 . Navigation, in turn, intricately depends on locomotion; however, current accounts suggest dissociation between hippocampal the details of locomotor processes. Specifically, thought to represent mainly higher-order cognitive variables such as position, speed direction movement 4–7 , whereas limb movements propel animal can be computed represented primarily...
Background Although extensive research has demonstrated the importance of excitatory granule neurons in dentate gyrus hippocampus normal learning and memory pathogenesis amnesia Alzheimer's disease (AD), role hilar GABAergic inhibitory interneurons, which control neuron activity, remains unclear. Methodology Principal Findings We explored function interneurons spatial by inhibiting their activity through Cre-dependent viral expression enhanced halorhodopsin (eNpHR3.0)—a light-driven chloride...
Apolipoprotein (apo) E4 is expressed in many types of brain cells, associated with age-dependent decline learning and memory humans, the major genetic risk factor for AD. To determine whether detrimental effects apoE4 depend on its cellular sources, we generated human apoE knock-in mouse models which APOE gene conditionally deleted astrocytes, neurons, or GABAergic interneurons. Here report that deletion astrocytes does not protect aged mice from apoE4-induced interneuron loss deficits. In...
Alzheimer's disease (AD) is characterized by progressive memory loss, and there a pressing need to identify early pathophysiological alterations that predict subsequent impairment. Hippocampal sharp-wave ripples (SWRs)—electrophysiological signatures of reactivation in the hippocampus—are compelling candidate for this purpose. Mouse models AD show reductions both SWR abundance associated slow gamma (SG) power during aging, but these have yet be directly linked impairments. In aged...
ABSTRACT Executing memory-guided behavior requires both the storage of information about experience and later recall that to inform choices. Awake hippocampal replay, when neural ensembles briefly reactivate a representation related prior experience, has been proposed critically contribute these memory-related processes. However, it remains unclear whether awake replay contributes memory function by promoting past experiences, facilitating planning based on an evaluation those or both. We...
Specific classes of GABAergic neurons play specific roles in regulating information processing the brain. In hippocampus, two major classes, parvalbumin-expressing (PV+) and somatostatin-expressing (SST+), differentially regulate endogenous firing patterns target subcellular compartments principal cells. How these flow throughout hippocampus is poorly understood. We hypothesize that PV+ SST+ interneurons dentate gyrus (DG) CA3 modulate output, thereby altering influence on CA1. find while...
New recording technologies and the potential for closed-loop experiments have led to an increasing demand computationally efficient accurate algorithms decode population spiking activity in multi-dimensional spaces. Exact point process filters can accurately low-dimensional signals, but are intractable high-dimensional signals. Approximate Gaussian efficient, inaccurate when signals complex distributions nonlinear dynamics. Even particle filter methods tend become inefficient distribution...
Hippocampal replay – the time-compressed, sequential reactivation of ensembles neurons related to past experience is a key neural mechanism memory consolidation. Replay typically coincides with characteristic pattern local field potential activity, sharp-wave ripple (SWR). Reduced SWR rates are associated cognitive impairment in multiple models neurodegenerative disease, suggesting that clinically viable intervention promote SWRs and would prove beneficial. We therefore developed...
The emergence of deep learning techniques has provided new tools for the analysis complex data in field neuroscience. In parallel, advanced statistical approaches like point-process modeling provide powerful analyzing spiking activity neural populations. How and machine compare when applied to remains largely unclear. this research, we performance a filter long short-term memory (LSTM) network decoding 2D movement trajectory rat using recorded from an ensemble hippocampal place cells. We...
Hippocampal replay – the time-compressed, sequential reactivation of ensembles neurons related to past experience is a key neural mechanism memory consolidation. Replay typically coincides with characteristic pattern local field potential activity, sharp-wave ripple (SWR). Reduced SWR rates are associated cognitive impairment in multiple models neurodegenerative disease, suggesting that clinically viable intervention promote SWRs and would prove beneficial. We therefore developed...
Animal behavior provides context for understanding disease models and physiology. However, that is often characterized subjectively, creating opportunity misinterpretation misunderstanding. For example, spatial alternation tasks are treated as paradigmatic tools examining memory; however, link actually an assumption. To test this assumption, we simulated a reinforcement learning (RL) agent equipped with perfect memory process. We found it learns simple task more slowly makes different errors...
Abstract Representations related to past experiences play a critical role in memory and decision-making processes. The rat hippocampus expresses these types of representations during sharp-wave ripple (SWR) events, previous work identified minority SWRs that contain “replay” spatial trajectories at ~20x the movement speed animal. Efforts understand replay typically make multiple assumptions about which events examine what sorts constitute replay. We therefore lack clear understanding both...
Humans can remember specific remote events without acting on them and influence which memories are retrieved based internal goals. However, animal models typically present sensory cues to trigger memory retrieval then assess action. Thus, it is difficult determine whether measured neural activity patterns relate the cue(s), memory, or behavior. We therefore asked retrieval-related could be generated in animals a behavioral report. focused hippocampal "place cells" primarily represent...